Vaccines

2024

Jump to: 2023, 2022, 2021

17 pages, 283 KiB

Open AccessArticle

Flares and Predicting Factors of Flares in Patients with Systemic Lupus Erythematosus Associated with Different Doses and Types of COVID-19 Vaccines

by Worawit Louthrenoo, Punsita Tangkum, Nuntana Kasitanon, Wanitcha Gumtorntip, Poramed Winichakoon, Supparat Konsamun and Antika Wongthanee

Vaccines 2024, 12(12), 1399; https://doi.org/10.3390/vaccines12121399 - 12 Dec 2024

Viewed by 686

Abstract

Objectives: To compare disease activity and flares among different doses and types of COVID-19 vaccines in systemic lupus erythematosus (SLE) patients. Methods: SLE patients in a lupus cohort, who received at least one dose of a COVID-19 vaccine (inactivated virus, adenovirus-vectored, or [...] Read more.

Objectives: To compare disease activity and flares among different doses and types of COVID-19 vaccines in systemic lupus erythematosus (SLE) patients. Methods: SLE patients in a lupus cohort, who received at least one dose of a COVID-19 vaccine (inactivated virus, adenovirus-vectored, or mRNA vaccines) between March and October 2022 joined this study. The data regarding disease activity and flares after each dose were reviewed and compared. Results: Two hundred and one SLE patients (524 total doses) were included in this study, with 201, 199, and 124 of them receiving 1, 2, and 3 doses of a vaccine, respectively, which comprised 183, 128, and 213 doses of inactivated virus, adenovirus-vectored, and mRNA vaccines, respectively. Regardless of vaccine dose or type, there were no significant changes in SLE disease activity pre- or post-vaccination. Flares were significantly more common after the 2nd and 3rd doses than after the 1st one (20.10% and 17.74% vs. 8.96%, p = 0.001, and p = 0.010, respectively), and after inactivated virus, adenovirus-vectored and mRNA vaccinations in 11.48%, 14.84%, and 17.84% of the patients (p = ns), respectively. However, the incidence rate of flares/100 patient-months was not different. The majority of flares were severe, with renal flares being the most frequent. Renal and mucocutaneous involvement and high SLE disease activity prior to the 1st vaccine dose were independent factors that predicted flares. Conclusions: Flares after COVID-19 vaccination were not uncommon. Most of the flares were severe, mainly due to renal flares. SLE patients should have stable low disease activity prior to receiving COVID-19 vaccine in order to avoid flares. Full article

12 pages, 622 KiB

Open AccessArticle

The Impact of COVID-19 Vaccination and Infection on the Exacerbation of Myasthenia Gravis

by Yuting Jiang, Jingsi Wang, Shengyao Su, Shu Zhang, Qi Wen, Yaye Wang, Ling Li, Jianxin Han, Nairong Xie, Haoran Liu, Yanan Sun, Yan Lu, Li Di, Min Wang, Min Xu, Hai Chen, Suobin Wang, Xinmei Wen, Wenjia Zhu and Yuwei Da

Vaccines 2024, 12(11), 1221; https://doi.org/10.3390/vaccines12111221 - 27 Oct 2024

Viewed by 1087

Abstract

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis [...] Read more.

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients. Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as “hospitalization” or “home management”; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423–7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity (p = 0.292) or MECI incidence (p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed. Full article

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2023

Jump to: 2024, 2022, 2021

11 pages, 1114 KiB

Open AccessArticle

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis

by Shih-Hsin Hsiao, Yuh-Mou Sue, Chih-Chin Kao, Hui-Wen Chang, Yen-Chung Lin, Ching-Sheng Hung, Yi-Chen Hsieh, Shiao-Ya Hong, Chi-Li Chung, Jer-Hwa Chang, Ying-Shih Su, Ming-Che Liu, Kevin Shu-Leung Lai, Ko-Ling Chien, Jude Chu-Chun Wang, Chung-Yi Cheng and Te-Chao Fang

Vaccines 2023, 11(7), 1161; https://doi.org/10.3390/vaccines11071161 - 27 Jun 2023

Cited by 1 | Viewed by 1851

Abstract

Background: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. Methods: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and [...] Read more.

Background: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. Methods: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). Results: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. Conclusion: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose. Full article

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9 pages, 821 KiB

Open AccessArticle

Effectiveness of Vaccination in Preventing COVID-19: A Community Study Comparing Four Vaccines

by Zoran Kokić, Predrag Kon and Olgica Djurković-Djaković

Vaccines 2023, 11(3), 544; https://doi.org/10.3390/vaccines11030544 - 24 Feb 2023

Cited by 1 | Viewed by 2599

Abstract

The course of the COVID-19 pandemic has been critically altered by the availability of vaccines. To assess the risk of COVID-19 in the vaccinated, as compared to the unvaccinated population, as well as the comparative effectiveness of the BBIBP-CorV (Sinopharm), BNT162b2 (Pfizer/BioNTech), Gam-COVID-Vac [...] Read more.

The course of the COVID-19 pandemic has been critically altered by the availability of vaccines. To assess the risk of COVID-19 in the vaccinated, as compared to the unvaccinated population, as well as the comparative effectiveness of the BBIBP-CorV (Sinopharm), BNT162b2 (Pfizer/BioNTech), Gam-COVID-Vac (Sputnik V) and ChAdOx1 (AstraZeneca) vaccines in the prevention of clinical infection, we carried out a retrospective study of the incidence of clinical COVID-19 in the Belgrade city municipality of Voždovac among both vaccinated and unvaccinated individuals during a 4-month period between 1 July and 31 October 2021. The study included all individuals with a symptomatic infection confirmed by a positive PCR and/or antigen test. Only those who received two vaccine doses were considered as vaccinated. The results showed that of the Voždovac population of 169,567, a total of 81,447 (48%) individuals were vaccinated by the end of the study. Vaccination coverage increased with age, ranging from 1.06% in those below age 18, to even 78.8% in those above 65 years of age. More than one half (57.5%) of all those vaccinated received BBIBP-CorV, while 25.2% received BNT162b2, 11.7% Gam-COVID-Vac and 5.6% ChAdOx1. The overall risk of infection of the vaccinated vs. the unvaccinated was 0.53 (95% CI 0.45–0.61). Compared to the incidence of COVID-19 of 8.05 per 1000 in the unvaccinated population, the relative risk in the vaccinated was 0.35 (95% CI 0.3–0.41). The overall VE was 65%, differing widely among age groups and by vaccine. VE was 79% for BNT162b2, 62% for BBIBP-CorV, 60% for ChAdOx1 and 54% for Gam-COVID-Vac. The VE for BBIBP-CorV and BNT162b2 increased with age. The obtained results demonstrate a significant overall effectiveness of anti-COVID-19 vaccination, which, however, varied significantly among the analyzed vaccines, and was the highest for BNT162b2. Full article

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10 pages, 966 KiB

Open AccessArticle

Adverse Reactions after Booster SARS-CoV-2 Vaccination Have Less Impact on Antibody Response than after Basic Vaccination Scheme

by Andrea Kanizsai, Laszlo Zavori, Tihamer Molnar, Margit Tőkés-Füzesi, Zoltan Szalai, Janos Berecz, Reka Varnai, Zoltan Peterfi, Attila Schwarcz and Peter Csecsei

Vaccines 2023, 11(1), 182; https://doi.org/10.3390/vaccines11010182 - 15 Jan 2023

Cited by 2 | Viewed by 2102

Abstract

Background: It is known that adverse reactions following SARS-CoV-2 vaccinations show a positive correlation with the subsequent antibody titer. However, it is not clear how the adverse reactions following the booster vaccination are related to the antibody levels that can be measured after [...] Read more.

Background: It is known that adverse reactions following SARS-CoV-2 vaccinations show a positive correlation with the subsequent antibody titer. However, it is not clear how the adverse reactions following the booster vaccination are related to the antibody levels that can be measured after a 3rd dose. The primary goal of this study was to investigate whether the adverse reactions following the booster vaccination show a correlation with subsequent antibody levels. Methods: Adverse reactions occurring within 7 days after the 3rd vaccination were recorded and the anti-SARS-CoV-2 spike protein immunoglobulin (Ig) level in the venous blood was measured on post-vaccination 14th, 60th and 120th days. Results: A total of 218 volunteers were included in the study. Main findings: (i) The adverse reactions that appeared after the booster dose did not show a positive correlation with the subsequent antibody level, except a correlation in the case of fever; (ii) there were more symptomatic patients in the group receiving heterologous booster vaccine, (iii) fever after the 2nd dose was independently associated with a reduction in the likelihood of COVID-19 positivity after the booster dose. Conclusion: No adverse reactions, but fever showed a correlation with the antibody level after the booster SARS-CoV-2 vaccine. Full article

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2022

Jump to: 2024, 2023, 2021

16 pages, 1070 KiB

Open AccessArticle

SARS-CoV-2 Infection Anxiety, Knowledge and Attitudes in University Degree Pregnant Women from Romania—A Cross-Sectional Observational Survey in the First Two Pandemic Years

by Madalina Preda, Rares Sebastian Dinu, Irina Prasacu and Loredana Sabina Cornelia Manolescu

Vaccines 2023, 11(1), 35; https://doi.org/10.3390/vaccines11010035 - 23 Dec 2022

Cited by 3 | Viewed by 2217

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a high economic cost, morbidity, and death toll. Due to high rates of mortality and morbidity from coronavirus disease 2019 (COVID-19), pregnant women were at particular risk during this pandemic. We designed and [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a high economic cost, morbidity, and death toll. Due to high rates of mortality and morbidity from coronavirus disease 2019 (COVID-19), pregnant women were at particular risk during this pandemic. We designed and conducted a cross-sectional observational survey in Romanian pregnant women to evaluate the outcome of the SARS-CoV-2 pandemic along with the preventive measures taken by authorities. We applied a 43-item questionnaire. We included 147 women over 18 years old from Romania who were pregnant or gave birth between March 2020 and March 2022. All pregnancies were monitored, most of them by a gynecologist, and only 23% faced rescheduled pregnancy visits. The majority (84%) were screened through the TORCH panel, 95.91% felt anxious because of the pandemic, 87% followed SARS-CoV2 preventive recommendations, and 82% were not infected with the coronavirus. Additionally, 80% were vaccinated against COVID-19. They felt the consequences of the pandemic through anxiety, and their level of anxiety influenced their vaccination decisions, the TORCH testing and the method of giving birth despite the level of education. Fortunately, their pregnancies were monitored properly, and there were no consequences noticed for fetuses at birth. Full article

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15 pages, 6294 KiB

Open AccessArticle

Dynamics of Antibody and T Cell Immunity against SARS-CoV-2 Variants of Concern and the Impact of Booster Vaccinations in Previously Infected and Infection-Naïve Individuals

by Michel R. Faas, Willem A. Mak, Hilde Y. Markus, Ellen M. van der Zwan, Marijke van der Vliet, Johannes G. M. Koeleman and David S. Y. Ong

Vaccines 2022, 10(12), 2132; https://doi.org/10.3390/vaccines10122132 - 13 Dec 2022

Cited by 10 | Viewed by 3500

Abstract

Despite previous coronavirus disease 2019 (COVID-19) vaccinations and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, SARS-CoV-2 still causes a substantial number of infections due to the waning of immunity and the emergence of new variants. Here, we assessed the SARS-CoV-2 spike subunit [...] Read more.

Despite previous coronavirus disease 2019 (COVID-19) vaccinations and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, SARS-CoV-2 still causes a substantial number of infections due to the waning of immunity and the emergence of new variants. Here, we assessed the SARS-CoV-2 spike subunit 1 (S1)-specific T cell responses, anti-SARS-CoV-2 receptor-binding domain (RBD) IgG serum concentrations, and the neutralizing activity of serum antibodies before and one, four, and seven months after the BNT162b2 or mRNA-1273 booster vaccination in a cohort of previously infected and infection-naïve healthcare workers (HCWs). Additionally, we assessed T cell responses against the spike protein of the SARS-CoV-2 Delta, Omicron BA.1 and BA.2 variants of concern (VOC). We found that S1-specific T cell responses, anti-RBD IgG concentrations, and neutralizing activity significantly increased one month after booster vaccination. Four months after booster vaccination, T cell and antibody responses significantly decreased but levels remained steady thereafter until seven months after booster vaccination. After a similar number of vaccinations, previously infected individuals had significantly higher S1-specific T cell, anti-RBD IgG, and neutralizing IgG responses than infection-naïve HCWs. Strikingly, we observed overall cross-reactive T cell responses against different SARS-CoV-2 VOC in both previously infected and infection-naïve HCWs. In summary, COVID-19 booster vaccinations induce strong T cell and neutralizing antibody responses and the presence of T cell responses against SARS-CoV-2 VOC suggest that vaccine-induced T cell immunity offers cross-reactive protection against different VOC. Full article

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Study populations and sampling time points. Blood samples were collected and immune responses were assessed at the following four time points: November 2021 (t0; approximately two weeks before receiving a booster vaccination), December 2021 (t1; one month post-booster vaccination), March 2022 (t2; four months post-booster vaccination), and June 2022 (t3; seven months post-booster vaccination). Full article ">Figure 2
SARS-CoV-2-specific T cell and antibody responses of previously infected HCWs two weeks and five months post-primary vaccinations. Previously infected HCWs (n = 32) are represented by individual data points. (A) T cell responses against SARS-CoV-2 S1 and N, (B) serum anti-RBD IgG concentrations, and (C) the neutralizing activity of serum antibodies against SARS-CoV-2 at two weeks and five months (i.e., t0) after primary vaccination series. Statistical significance was assessed with a Wilcoxon test. Full article ">Figure 3
SARS-CoV-2-specific T cell and antibody responses of previously infected HCWs before and after booster vaccination. Immune responses of previously infected HCWs (n = 26) were assessed at median 1 (IQR 1–7) day before (t0) and 27 (IQR 24–29) days after (t1) receiving the BNT162b2 or mRNA-1273 booster vaccination. Each data point represents an individual HCW. (A) T cell responses against SARS-CoV-2 S1 and N. (B) Serum anti-RBD IgG concentrations. (C) Neutralizing activity of serum antibodies against SARS-CoV-2. (D) Association between SARS-CoV-2 S1-specific T cell responses and anti-RBD IgG concentrations at t0 and t1. (E) Association between the neutralizing activities and anti-RBD IgG concentrations at t0 and t1. Statistical significance between paired data was assessed with a Wilcoxon test (A–C) and associations were assessed by Spearman’s rank correlation (D,E). Full article ">Figure 4
SARS-CoV-2-specific T cell and antibody responses of previously infected HCWs at t1, t2, and t3. Immune responses of previously infected HCWs were assessed median 27 (IQR 22–28) days (t1), 125 (IQR 118–126) days (t2), and 221 (IQR 204–213) days (t3) after receiving BNT162b2 or mRNA-1273 booster vaccination. (A) SARS-CoV-2 S1-specific T cell responses, (B) serum anti-RBD IgG concentrations, and (C) neutralizing activity against SARS-CoV-2 at t1 and t2 (n = 19). (D) SARS-CoV-2 S1-specific and (E) serum anti-RBD IgG concentrations at t2 and t3 (n = 19). Statistical significance was assessed with a Wilcoxon test. Full article ">Figure 5
SARS-CoV-2-specific T cell and antibody responses of previously infected, recently infected, and infection-naïve HCWs. Immune responses were assessed at t2 (median 126 (IQR 122–131) days after receiving BNT162b2 or mRNA-1273 booster vaccination) and t3 (median 209 (IQR 204–212) days after receiving BNT162b2 or mRNA-1273 booster vaccination). (A) SARS-CoV-2 S1-specific T cell responses at t2 of previously infected (n = 22), recently infected (n = 14), and infection-naïve HCWs (n = 24). (B) Anti-RBD serum IgG concentrations at t2 of previously infected (n = 22), recently infected (n = 14), and infection-naïve HCWs (n = 24). (C) Neutralizing activity against SARS-CoV-2 RBD at t2 of previously infected (n = 21), recently infected (n = 12), and infection-naïve HCWs (n = 23). (D) T cell responses against SARS-CoV-2 S1 and N at t3 between previously infected (n = 21), recently infected (n = 11), and infection-naïve HCWs (n = 21). (E) Anti-RBD serum IgG concentrations at t3 between previously infected (n = 21), recently infected (n = 11), and infection-naïve HCWs (n = 21). Indicated is the median with IQR and statistical significance was assessed with a Kruskal–Wallis test with Dunn’s multiple comparison test. (F) Percentages of serum anti-N IgG-positive previously infected HCWs (n = 21) assessed at June 2020, June 2021, and March 2022 (t2). Full article ">Figure 6
T cell responses against wild-type spike and VOC-mutated spike proteins. At t3, the PBMCs of previously infected (n = 21), recently infected (n = 11), and infection-naïve (n = 21) HCWs were stimulated with SARS-CoV-2 Omicron BA.1, Omicron BA.2, and Delta mutation spike peptide pools and corresponding SARS-CoV-2 wildtype (WT) spike peptide pools. (A) T cell responses against the SARS-CoV-2 Omicron BA.1 spike and corresponding WT spike peptide pools. (B) T cell responses against the SARS-CoV-2 Omicron BA.2 spike and corresponding WT spike peptide pools. (C) T cell responses against the SARS-CoV-2 Delta spike and corresponding WT spike peptide pools. Statistical significance was assessed with a Mann–Whitney test. (D) T cell responses against SARS-CoV-2 Omicron BA.1, Omicron BA.2, and Delta spike mutation peptide pools between previously infected, recently infected, and infection-naive HCWs. Indicated is the median with IQR and statistical significance was assessed through a Kruskal–Wallis test with Dunn’s multiple comparison test. Full article ">

14 pages, 4446 KiB

Open AccessArticle

Durability of Immune Response to ChAdOx1-nCoV-19 Vaccine in Solid Cancer Patients Undergoing Anticancer Treatment

by Passakorn Wanchaijiraboon, Nattaya Teeyapun, Nussara Pakvisal, Panot Sainamthip, Thiti Susiriwatananont, Nicha Zungsontiporn, Nungruthai Suntronwong, Preeyaporn Vichaiwattana, Worata Klinsawat, Nasamon Wanlapakorn, Suebpong Tanasanvimon, Virote Sriuranpong, Yong Poovorawan and Sutima Luangdilok

Vaccines 2022, 10(10), 1662; https://doi.org/10.3390/vaccines10101662 - 5 Oct 2022

Cited by 2 | Viewed by 2372

Abstract

There are limited data available about the durability of the immune response after administration of the widely used adenovirus-vectored ChAdOx1-nCoV-19 vaccine in cancer patients. This prospective longitudinal observational study analyzed follow-up data of immunogenic responses 12 weeks after the second dose of the [...] Read more.

There are limited data available about the durability of the immune response after administration of the widely used adenovirus-vectored ChAdOx1-nCoV-19 vaccine in cancer patients. This prospective longitudinal observational study analyzed follow-up data of immunogenic responses 12 weeks after the second dose of the ChAdOx1-nCoV-19 vaccine in 290 oncological patients compared to healthy controls. The study aimed to assess the persistence of the humoral immune response three months after the second dose, and omicron neutralization was also evaluated. Three months after completion of the second vaccine dose, the geometric mean titer of SARS-CoV-2 binding total Ig statistically decreased by 42% compared to those at 4 weeks, and was lower than that of the healthy control. Six percent of patients became seronegative for anti-RBD total Ig. Only 5% (2 of 40 samples) tested positive for surrogate neutralization against SAR-CoV-2 Omicron BA.2. Across different therapy types, a waning in immunogenicity was observed within three months after the second dose of the ChAdOx1 nCoV-19 vaccine, rendering it insufficient at that point to protect against the SAR-CoV-2 Omicron BA.2 variant. Full article

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11 pages, 4966 KiB

Open AccessArticle

Immunogenicity after a Third COVID-19 mRNA Booster in Solid Cancer Patients Who Previously Received the Primary Heterologous CoronaVac/ChAdOx1 Vaccine

by Sutima Luangdilok, Passakorn Wanchaijiraboon, Nussara Pakvisal, Thiti Susiriwatananont, Nicha Zungsontiporn, Virote Sriuranpong, Panot Sainamthip, Nungruthai Suntronwong, Preeyaporn Vichaiwattana, Nasamon Wanlapakorn, Yong Poovorawan, Nattaya Teeyapun and Suebpong Tanasanvimon

Vaccines 2022, 10(10), 1613; https://doi.org/10.3390/vaccines10101613 - 26 Sep 2022

Cited by 8 | Viewed by 2632

Abstract

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were [...] Read more.

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens. Full article

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(A) Study flow diagram (B) SARS-CoV-2 binding antibody response at post-third mRNA COVID-19 vaccine following the primary heterologous CoronaVac/ChAdOx1 versus ChAdOx1/ChAdOx1 vaccination schedules. Anti-RBD IgG levels ≥ 7.1 BAU/mL (equal to 50 AU/mL) were considered positive, whereas levels >300 BAU/mL were considered as adequate response. a Mann-Whitney test, b Wilcoxon signed rank test. Full article ">Figure 2
(A,B) SARS-CoV-2 binding antibody response SARS-CoV-2 binding antibody response at post-third mRNA COVID-19 vaccine following the heterologous CoronaVac/ChAdOx1 vaccination in cancer patients versus healthy controls (A) and aged match subset analysis (B). (C) SARS-CoV-2 binding antibody response at post-third mRNA COVID-19 vaccine following the primary CoronaVac/ChAdOx1 vaccination in cancer patients stratified by types of mRNA COVID-19 vaccines and types of anticancer treatment. (D) Vaccine-related reactogenicity after the CoronaVac/ChAdOx1/mRNA vaccination in cancer patients. a Mann-Whitney test, b Wilcoxon signed rank test. Full article ">Figure 2 Cont.
(A,B) SARS-CoV-2 binding antibody response SARS-CoV-2 binding antibody response at post-third mRNA COVID-19 vaccine following the heterologous CoronaVac/ChAdOx1 vaccination in cancer patients versus healthy controls (A) and aged match subset analysis (B). (C) SARS-CoV-2 binding antibody response at post-third mRNA COVID-19 vaccine following the primary CoronaVac/ChAdOx1 vaccination in cancer patients stratified by types of mRNA COVID-19 vaccines and types of anticancer treatment. (D) Vaccine-related reactogenicity after the CoronaVac/ChAdOx1/mRNA vaccination in cancer patients. a Mann-Whitney test, b Wilcoxon signed rank test. Full article ">Figure 3
ELISA-based surrogate neutralization against Omicron BA2 variant in response to the CoronaVac/ChAdOx1/mRNA versus the ChAdOx1/ChAdOx1/mRNA vaccination in cancer patients. Data are reported as the median and 95%CI of percentage of inhibition between human ACE-2 and RBD protein. The cut-off value of 30% indicates the presence of detectable neutralization according to the manufacturer’s (cPass, Genscript) protocol. Data points represent individual samples. The pink color represents chemotherapy and the blue color represents treatment with hormonal therapy/biologics. a Mann-Whitney test. Full article ">

13 pages, 1895 KiB

Open AccessArticle

Perceptions of COVID-19 Vaccine, Racism, and Social Vulnerability: An Examination among East Asian Americans, Southeast Asian Americans, South Asian Americans, and Others

by Tsu-Yin Wu, Olivia Ford, Alice Jo Rainville, Xining Yang, Chong Man Chow, Sarah Lally, Rachel Bessire and Jessica Donnelly

Vaccines 2022, 10(8), 1333; https://doi.org/10.3390/vaccines10081333 - 17 Aug 2022

Cited by 12 | Viewed by 2880

Abstract

As COVID-19 vaccines are readily available and most U.S. adults who are enthusiastic about the vaccine have received it, motivating those who have not been vaccinated to accept it has become a challenge. The purpose of this study was to understand the mechanisms [...] Read more.

As COVID-19 vaccines are readily available and most U.S. adults who are enthusiastic about the vaccine have received it, motivating those who have not been vaccinated to accept it has become a challenge. The purpose of this study was to understand the mechanisms behind COVID-19 vaccine acceptance in Asian American ethnic groups, including how sociodemographic characteristics and racism predict COVID-19 and vaccine perceptions. The study also examined associations between social vulnerability and COVID-19 and vaccine perceptions. Social vulnerability is defined as the degree to which a community is able to prepare and respond to a natural or man-made disaster. This cross-sectional study used community-based survey data collected from April to September 2021. Study measures included demographics, perceptions of COVID-19 and COVID-19 vaccines, and racism-related experiences. The results showed that, compared to Non-Asians, East Asians reported that they had significantly more challenges accessing COVID-19 vaccines, and South Asians reported significantly higher safety concerns about COVID-19 vaccines. Our study also found that racism experience mediates the association between race/ethnicity and safety concerns about COVID-19 vaccines. Three Asian subgroups (East Asians, South Asians, and Southeast Asians) experienced more racism (compared to Non-Asians), and more experience of racism was related to greater safety concerns. Geographical Information System (GIS) maps revealed that residents of lower social vulnerability index (SVI) areas reported fewer unfairness perceptions and that higher SVI areas had lower vaccine accessibility and trust in public health agencies. Our study advances the understanding of racism, social vulnerability, and COVID-19 vaccine-related perceptions among Asian Americans. The findings have implications for policymakers and community leaders with respect to tailoring COVID-19 program efforts for socially vulnerable populations and Asian American groups that experience greater challenges regarding vaccine safety concerns and accessibility. Full article

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15 pages, 1116 KiB

Open AccessArticle

Retrospective Cohort Study of the Effectiveness of the Sputnik V and EpiVacCorona Vaccines against the SARS-CoV-2 Delta Variant in Moscow (June–July 2021)

by Olga Matveeva and Alexander Ershov

Vaccines 2022, 10(7), 984; https://doi.org/10.3390/vaccines10070984 - 21 Jun 2022

Cited by 15 | Viewed by 7329

Abstract

The goal of this study was to evaluate the epidemiological effectiveness of the Sputnik V and EpiVacCorona vaccines against COVID-19. This work is a retrospective cohort study of COVID-19 patients. The cohort created by the Moscow Health Department included more than 300,000 infected [...] Read more.

The goal of this study was to evaluate the epidemiological effectiveness of the Sputnik V and EpiVacCorona vaccines against COVID-19. This work is a retrospective cohort study of COVID-19 patients. The cohort created by the Moscow Health Department included more than 300,000 infected people who sought medical care in June and July 2021. Analysis of data revealed a tendency for the increase in the Sputnik V vaccine effectiveness (VE) as the severity of the disease increased. Protection was the lowest for mild disease, and it was more pronounced for severe disease. We also observed a decrease in VE with increasing age. For the youngest group (18–50 years old), the estimated VE in preventing death in June 2021 was 95% (95% CI 64–100), and for the older group (50+ years old), it was 74% (95% CI 67–87). The estimated protection against a severe form of the disease in the 18–50-year-old group was above 81% (CI 95% 72–93), and in the 50+ years-old group, it was above 68% (CI 95% 65–82). According to our analysis, EpiVacCorona proved to be an ineffective vaccine and therefore cannot protect against COVID-19. Full article

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15 pages, 2240 KiB

Open AccessArticle

A Needs-Based Analysis of Teaching on Vaccinations and COVID-19 in German Medical Schools

by Franziska Baessler, Ali Zafar, Katharina Mengler, Ricarda Nadine Natus, Anne Josephine Dutt, Manuel Kuhlmann, Emre Çinkaya and Simon Hennes

Vaccines 2022, 10(6), 975; https://doi.org/10.3390/vaccines10060975 - 19 Jun 2022

Cited by 4 | Viewed by 2803

Abstract

The COVID-19 pandemic highlights the need for improving public confidence in vaccines. Academic gaps and redundancies on vaccinations must be identified to revise the medical curriculum for up-to-date training of medical students. This cross-sectional survey assessed the status of vaccine-related teaching in general [...] Read more.

The COVID-19 pandemic highlights the need for improving public confidence in vaccines. Academic gaps and redundancies on vaccinations must be identified to revise the medical curriculum for up-to-date training of medical students. This cross-sectional survey assessed the status of vaccine-related teaching in general and specific to COVID-19 in medical schools across Germany. A total of 4313 medical students completed a questionnaire comprising items on national learning goals and perceived needs for teaching on vaccinations. Mixed methods were used to analyse data quantitatively for relative frequencies (%) and correlations between teaching items and semesters (Spearman’s rho), and qualitatively (content analysis). Our findings showed that 38.92% of the students were dissatisfied with teaching on vaccine-preventable diseases, but the perceived satisfaction increased in later semesters (r = 0.46, p < 0.001). Moreover, 75.84% and 68.15% of the students were dissatisfied with teaching related to vaccine scepticism and vaccine-related communication strategies, respectively. Furthermore, 63.79% reported dissatisfaction with teaching on COVID-19 disease and 72.93% with teaching on COVID-19 vaccines. A total of 79.12% stated they educated others on COVID-19 and its vaccines and 75.14% felt responsible to do so. A majority of the medical students were dissatisfied with teaching on dealing with vaccine scepticism, communication strategies and COVID-19 vaccines. We recommend practice-oriented vaccine education, especially for teaching communication skills to medical students. Full article

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11 pages, 1227 KiB

Open AccessArticle

Reduction of Precautionary Behaviour following Vaccination against COVID-19: A Test on a British Cohort

by Olivier Desrichard, Lisa Moussaoui and Nana Ofosu

Vaccines 2022, 10(6), 936; https://doi.org/10.3390/vaccines10060936 - 12 Jun 2022

Cited by 9 | Viewed by 1952

Abstract

Background: There is a risk that people vaccinated against COVID-19 will drop or reduce their precautionary behaviours (i.e., a phenomenon of risk homeostasis). Our aim is to assess the occurrence of this effect in a cohort of UK participants who were interviewed 141 [...] Read more.

Background: There is a risk that people vaccinated against COVID-19 will drop or reduce their precautionary behaviours (i.e., a phenomenon of risk homeostasis). Our aim is to assess the occurrence of this effect in a cohort of UK participants who were interviewed 141 days before and 161 days after the start of the vaccination programme. Methods: Of the 765 people who could be followed up before and after the start of the programme and whose vaccination status was known, 178 had not received any injection and 583 were more or less advanced in the process (one vs. two doses since less vs. more than 14 days). The frequency of 14 precautionary behaviours was assessed at both times of measurement, as well as potential covariates (gender, age, comorbidities and history of COVID-19). Results: Controlling for covariates, we didn’t find more decrease in precautionary behaviours among vaccinated individuals, regardless of how far along they were in the process. Conclusion: The results observed in this sample show little risk for a massive change in behaviours among early vaccinated individuals. The pressure to adopt precautionary behaviours remains strong and probably prevents the emergence of a risk homeostasis effect. Full article

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9 pages, 265 KiB

Open AccessArticle

Risk of Myocarditis and Pericarditis among Young Adults following mRNA COVID-19 Vaccinations

by Abdallah Alami, Daniel Krewski, Donald Mattison, Kumanan Wilson, Christopher A. Gravel, Paul J. Villeneuve, Patrick J. Farrell, James A. G. Crispo and Santiago Perez-Lloret

Vaccines 2022, 10(5), 722; https://doi.org/10.3390/vaccines10050722 - 5 May 2022

Cited by 14 | Viewed by 4471

Abstract

There have been reports of cases of myocarditis and pericarditis as rare complications following mRNA COVID-19 vaccinations among young adults. While most reported cases are mild, this potential vaccine safety signal should be closely monitored. Using data from the CDC and the Vaccine [...] Read more.

There have been reports of cases of myocarditis and pericarditis as rare complications following mRNA COVID-19 vaccinations among young adults. While most reported cases are mild, this potential vaccine safety signal should be closely monitored. Using data from the CDC and the Vaccine Adverse Event Reporting System (VAERS), we calculated the combined reporting rate of myocarditis and pericarditis stratified by age group, sex, vaccine dose, and manufacturer, and compared these rates to the crude background incidence rates. Compared to the general population prior to the administration of the first COVID-19 vaccines in December 2020, we identified a higher-than-expected reporting rate of myocarditis and pericarditis following mRNA vaccination; the risk was higher after a second vaccine dose, higher in males than in females, and decreased with age. The highest risk was seen in males 12–17 years of age with approximately 6 cases per 100,000 second doses. Our findings suggest an increased risk of myocarditis and pericarditis in young males following a second dose of an mRNA COVID-19 vaccine. Since these findings are based on safety signals derived from passive surveillance data, confirmatory epidemiological studies should be undertaken. Full article

15 pages, 2153 KiB

Open AccessArticle

Dermal Delivery of a SARS-CoV-2 Subunit Vaccine Induces Immunogenicity against Variants of Concern

by Christopher L. D. McMillan, Armira Azuar, Jovin J. Y. Choo, Naphak Modhiran, Alberto A. Amarilla, Ariel Isaacs, Kate E. Honeyman, Stacey T. M. Cheung, Benjamin Liang, Maria J. Wurm, Paco Pino, Joeri Kint, Germain J. P. Fernando, Michael J. Landsberg, Alexander A. Khromykh, Jody Hobson-Peters, Daniel Watterson, Paul R. Young and David A. Muller

Vaccines 2022, 10(4), 578; https://doi.org/10.3390/vaccines10040578 - 8 Apr 2022

Cited by 8 | Viewed by 3874

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to disrupt essential health services in 90 percent of countries today. The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research [...] Read more.

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to disrupt essential health services in 90 percent of countries today. The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research since antibodies directed against the S protein were found to neutralize the virus. However, as new variants emerge, mutations within the spike protein have given rise to potential immune evasion of the response generated by the current generation of SARS-CoV-2 vaccines. In this study, a modified, HexaPro S protein subunit vaccine, delivered using a needle-free high-density microarray patch (HD-MAP), was investigated for its immunogenicity and virus-neutralizing abilities. Mice given two doses of the vaccine candidate generated potent antibody responses capable of neutralizing the parental SARS-CoV-2 virus as well as the variants of concern, Alpha and Delta. These results demonstrate that this alternative vaccination strategy has the potential to mitigate the effect of emerging viral variants. Full article

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Characterization of the SARS CoV-2 HexaPro S protein. (a) Analysis of HexaPro S protein on size-exclusion chromatography (SEC), with a single peak at 16.6 min and purity of 98%. A mixture of thyroglobulin (669 kDa), ferritin (440 kDa), aldolase (158 kDa), conalbumin (75 kDa), ovalbumin (43 kDa), and carbonic anhydrase (29 kDa) proteins were used as standards. (b) SDS-PAGE gel showing a band for the HexaPro S protein. (c) Negative-stain electron microscopy (Bar = 100 nm) of the HexaPro S protein. Antibody binding to (d) RBD (1047, 2M-10B11, CR3022, S309, and hACE2), (e) N-terminal domain (NTD; 2-17 and 1-22), and (f) S2 subunit (mAb 2.8 and mAb 18C2). Full article ">Figure 2
HexaPro S protein-based vaccine and its application using HD-MAP. (a) HD-MAPs containing 5000 solid polymer microprojection arrays to deliver vaccine into the cutaneous layer of the skin. (b) Delivery efficiency of antigen into the skin using HD-MAPs coated with SARS CoV-2 HexaPro S protein and QS-21-adjuvanted SARS CoV-2 HexaPro S protein (n = 5, each) was measured by comparing the remaining protein from the delivered HD-MAPs to undelivered HD-MAPs using capture ELISA. Full article ">Figure 3
Immune responses in BALB/c mice following the vaccination with excipients (negative control), HexaPro S protein, and HexaPro S protein + QS-21 via intradermal injection (i.d.) or HD-MAP application (n = 8, each), (a) vaccination schedule. Serum was collected after primary immunization and first boost (on day 20 and 42, respectively) and analyzed for (b) serum IgG antibody titers against HexaPro S protein and HexaPro S protein derived from Alpha and Delta variants by ELISA. Serum and bronchoalveolar lavage (BAL) collected on day 42 were analyzed for (c) serum virus neutralization by plaque reduction neutralization test (PRNT) against the parental SARS-CoV-2 isolate, an Alpha variant, and a Delta variant, and (d) BAL virus neutralization by PRNT against ancestral SARS-CoV-2 variant, respectively. Each point represents an individual biological replicate (mouse) performed on a single ELISA assay; bars represent the average antigen-specific IgG antibody titers (EC50); error bars represent the SD; the LoD line represents the assay limit of detection. Statistical analysis was performed using one-way ANOVA with Tukey’s multiple comparison post hoc test ((*) p < 0.05, (***) p < 0.001, (****) p < 0.0001 and non-significant (ns)). Full article ">

14 pages, 273 KiB

Open AccessArticle

An Association Study of HLA with the Kinetics of SARS-CoV-2 Spike Specific IgG Antibody Responses to BNT162b2 mRNA Vaccine

by Seik-Soon Khor, Yosuke Omae, Junko S. Takeuchi, Ami Fukunaga, Shohei Yamamoto, Akihito Tanaka, Kouki Matsuda, Moto Kimura, Kenji Maeda, Gohzoh Ueda, Tetsuya Mizoue, Mugen Ujiie, Hiroaki Mitsuya, Norio Ohmagari, Wataru Sugiura and Katsushi Tokunaga

Vaccines 2022, 10(4), 563; https://doi.org/10.3390/vaccines10040563 - 5 Apr 2022

Cited by 8 | Viewed by 2963

Abstract

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms [...] Read more.

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4⁺ and CD8⁺ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017; Odd ratio (OR) 2.80, 95%confidence interval (CI) 1.05–7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2, while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95%CI 0.05–0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058; OR 0.42, 95%CI 0.15–1.16), B*52:01:01 (p = 0.031; OR 0.38, 95%CI 0.14–1.03), DQA1*03:02:01 (p = 0.028; OR 0.39, 95%CI 0.15–1.00) and DPB1*02:01:02 (p = 0.024; OR 0.45, 95%CI 0.21–0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination. Full article

10 pages, 1803 KiB

Open AccessArticle

Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

by Ryousuke Koike, Michiru Sawahata, Yosikazu Nakamura, Yushi Nomura, Otohiro Katsube, Koichi Hagiwara, Seiji Niho, Norihiro Masuda, Takaaki Tanaka and Kumiya Sugiyama

Vaccines 2022, 10(3), 451; https://doi.org/10.3390/vaccines10030451 - 15 Mar 2022

Cited by 9 | Viewed by 2914

Abstract

Objective: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan. Methods: We enrolled 378 healthcare workers (255 [...] Read more.

Objective: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan. Methods: We enrolled 378 healthcare workers (255 women and 123 men) whose Ab titers were analyzed 3 and 6 months after the second dose in our previous study and whose characteristics and adverse effects were collected previously by using a structured self-report questionnaire. Results: The workers’ median age was 44 years. Although injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first dose. Multivariate analysis showed that fever was significantly correlated with female participants for the second dose (odds ratio (OR), 2.139; 95% confidence interval (95% CI), 1.185–3.859), older age for the first dose (OR, 0.962; 95% CI, 0.931–0.994) and second dose (OR, 0.957; 95% CI, 0.936–0.979), and dyslipidemia for the first dose (OR, 8.750; 95% CI, 1.814–42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with a fever than in those without a fever after the first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were, respectively, 21.7% and 19.3% higher in the group in which an anti-inflammatory agent was used than in the group without the use of an anti-inflammatory agent. Conclusion: Participants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects. Full article

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8 pages, 1377 KiB

Open AccessCommunication

COVID-19 Breakthrough Infection after Inactivated Vaccine Induced Robust Antibody Responses and Cross-Neutralization of SARS-CoV-2 Variants, but Less Immunity against Omicron

by Nungruthai Suntronwong, Ritthideach Yorsaeng, Jiratchaya Puenpa, Chompoonut Auphimai, Thanunrat Thongmee, Preeyaporn Vichaiwattana, Sitthichai Kanokudom, Thaneeya Duangchinda, Warangkana Chantima, Pattarakul Pakchotanon, Suvichada Assawakosri, Pornjarim Nilyanimit, Sirapa Klinfueng, Lakkhana Wongsrisang, Donchida Srimuan, Thaksaporn Thatsanatorn, Natthinee Sudhinaraset, Nasamon Wanlapakorn and Yong Poovorawan

Vaccines 2022, 10(3), 391; https://doi.org/10.3390/vaccines10030391 - 3 Mar 2022

Cited by 18 | Viewed by 4635

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with [...] Read more.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 77), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68–100 days). Blood samples were collected at a median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants, including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2), were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which exceeds 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant. Full article

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SARS-CoV-2-specific binding antibody responses and neutralizing activities. Immune response of individuals with SARS-CoV-2 breakthrough infection (CV + CV + Infection) was compared to those with fully vaccinated CoronaVac vaccines without infection (CV + CV) and those who received AZD1222 as third booster (CV + CV + AZ). Serum (a) anti-RBD Ig activity, (b) anti-RBD IgG-binding antibody units. The results are shown as Geometric mean titres with 95% CIs. The cut-off value is indicated as dotted lines. Statistics were calculated using one-way ANOVA with Bonferroni correction. *** p < 0.001. Full article ">Figure 2
Neutralizing activities against (a) wild-type, (b) B.1.1.7-alpha, (c) B.1.351-beta, and (d) B.1.617.2-delta using surrogate virus neutralization test (sVNT). The fully vaccinated individuals with two doses of CoronaVac (CV+CV), the fully vaccinated individuals with two doses of CoronaVac then administered a third vaccination with AZD1222 (CV+CV+AZ), and the fully vaccinated individuals with two doses of CoronaVac followed by SARS-CoV-2 breakthrough infection (CV+CV+infection) were compared. Median values with IQRs are shown as horizontal bars. Dotted lines indicate cut-off values, and grey shaded areas depict values under the cut-off. Statistics were calculated using Kruskal–Wallis tests with Dunn’s post hoc correction. * p < 0.05, ** p < 0.01, *** p < 0.001. ns indicates no statistical significance. Full article ">Figure 3
Live SARS-CoV-2 serum dilution titres were determined against B.1.617.2-delta and B.1.1.529-omicron in serum samples from individuals with breakthrough infection determined using focus reduction neutralization test 50 values (FRNT50). Number indicates the geometric mean titres with 95% CIs. Statistics were calculated using Wilcoxon matched pair signed rank test. *** p < 0.001. Full article ">

36 pages, 2451 KiB

Open AccessArticle

Reported Adverse Effects and Attitudes among Arab Populations Following COVID-19 Vaccination: A Large-Scale Multinational Study Implementing Machine Learning Tools in Predicting Post-Vaccination Adverse Effects Based on Predisposing Factors

by Ma’mon M. Hatmal, Mohammad A. I. Al-Hatamleh, Amin N. Olaimat, Rohimah Mohamud, Mirna Fawaz, Elham T. Kateeb, Omar K. Alkhairy, Reema Tayyem, Mohamed Lounis, Marwan Al-Raeei, Rasheed K. Dana, Hamzeh J. Al-Ameer, Mutasem O. Taha and Khalid M. Bindayna

Vaccines 2022, 10(3), 366; https://doi.org/10.3390/vaccines10030366 - 26 Feb 2022

Cited by 42 | Viewed by 9635

Abstract

Background: The unprecedented global spread of coronavirus disease 2019 (COVID-19) has imposed huge challenges on the healthcare facilities, and impacted every aspect of life. This has led to the development of several vaccines against COVID-19 within one year. This study aimed to assess [...] Read more.

Background: The unprecedented global spread of coronavirus disease 2019 (COVID-19) has imposed huge challenges on the healthcare facilities, and impacted every aspect of life. This has led to the development of several vaccines against COVID-19 within one year. This study aimed to assess the attitudes and the side effects among Arab communities after receiving a COVID-19 vaccine and use of machine learning (ML) tools to predict post-vaccination side effects based on predisposing factors. Methods: An online-based multinational survey was carried out via social media platforms from 14 June to 31 August 2021, targeting individuals who received at least one dose of a COVID-19 vaccine from 22 Arab countries. Descriptive statistics, correlation, and chi-square tests were used to analyze the data. Moreover, extensive ML tools were utilized to predict 30 post vaccination adverse effects and their severity based on 15 predisposing factors. The importance of distinct predisposing factors in predicting particular side effects was determined using global feature importance employing gradient boost as AutoML. Results: A total of 10,064 participants from 19 Arab countries were included in this study. Around 56% were female and 59% were aged from 20 to 39 years old. A high rate of vaccine hesitancy (51%) was reported among participants. Almost 88% of the participants were vaccinated with one of three COVID-19 vaccines, including Pfizer-BioNTech (52.8%), AstraZeneca (20.7%), and Sinopharm (14.2%). About 72% of participants experienced post-vaccination side effects. This study reports statistically significant associations (p < 0.01) between various predisposing factors and post-vaccinations side effects. In terms of predicting post-vaccination side effects, gradient boost, random forest, and XGBoost outperformed other ML methods. The most important predisposing factors for predicting certain side effects (i.e., tiredness, fever, headache, injection site pain and swelling, myalgia, and sleepiness and laziness) were revealed to be the number of doses, gender, type of vaccine, age, and hesitancy to receive a COVID-19 vaccine. Conclusions: The reported side effects following COVID-19 vaccination among Arab populations are usually non-life-threatening; flu-like symptoms and injection site pain. Certain predisposing factors have greater weight and importance as input data in predicting post-vaccination side effects. Based on the most significant input data, ML can also be used to predict these side effects; people with certain predicted side effects may require additional medical attention, or possibly hospitalization. Full article

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Participants’ health status indicators and their perceptions towards COVID-19 vaccines before receiving a COVID-19 vaccine. Chart (A) represents the most common chronic diseases that were reported by participants. (B–E) show proportions of participants who are smokers, have food and/or drug allergies, had experienced COVID-19 infection, had experienced COVID-19 vaccine hesitancy and related fears, respectively. (F) shows frequencies of COVID-19 vaccines preferred by participants, while (G) shows the credible sources of information about COVID-19 vaccines among them. Full article ">Figure 2
Participants’ post-vaccination information. (A) Interval between receiving a COVID-19 vaccine and participating in this study (n = 10,064). (B) Time of COVID-19 vaccine breakthrough infection (n = 471). (C) Characterization of participants who experienced COVID-19 vaccine breakthrough infections based on the type of vaccine and number of doses (n = 471; 4.7%). * The perception was calculated out of the total number of participants who experienced vaccine breakthrough infection (n = 471); ** the perception was calculated out of the total number of participants who received the vaccine (<a href="#vaccines-10-00366-t003" class="html-table">Table 3</a>). Full article ">Figure 3
Severity of side effects following COVID-19 vaccination. Full article ">Figure 4
Side effects of COVID-19 vaccines. (A), the most common post-vaccination side effects; (B), interval between receiving a COVID-19 vaccine and experiencing side effects; (C), duration of post-vaccination side effects; (D), coping responses to post-vaccination side effects. Full article ">Figure 5
Participants’ responses to belief-based questions after COVID-19 vaccination. Full article ">

7 pages, 208 KiB

Open AccessCommunication

Evaluation of Simple Lateral Flow Immunoassays for Detection of SARS-CoV-2 Neutralizing Antibodies

by Olaf Nickel, Alexandra Rockstroh, Stephan Borte and Johannes Wolf

Vaccines 2022, 10(3), 347; https://doi.org/10.3390/vaccines10030347 - 23 Feb 2022

Cited by 5 | Viewed by 2158

Abstract

Immunization for the generation of protective antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged to be highly effective in preventing hospital admission, need for intensive care treatment and high mortality in the current SARS-CoV-2 pandemic. Lateral flow immune assays (LFIAs) [...] Read more.

Immunization for the generation of protective antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged to be highly effective in preventing hospital admission, need for intensive care treatment and high mortality in the current SARS-CoV-2 pandemic. Lateral flow immune assays (LFIAs) offer a simple and competitive option to monitor antibody production after vaccination. Here, we compared the diagnostic performance of three different lateral flow assays in detecting nucleocapsid protein (NP), S1 subunit (S1) and receptor binding domain (pseudo)-neutralizing antibodies (nRBD) in sera of 107 health care workers prior (V1), two weeks (V2) after first vaccination with BNT162b2 as well as three weeks (V3) and eight months later (V4). In sera at V1, overall specificity was >99%. At V3, LFIAs showed sensitivities between 98.1 and 100%. The comparison of S1 and nRBD LFIA with S1 ELISA and a focus reduction neutralization assay (FRNT) revealed high concordance at V3. Thus, the use of lateral flow immunoassays appears to have reasonable application in the short-term follow-up after vaccination for SARS-CoV-2. Full article

16 pages, 1308 KiB

Open AccessArticle

Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome

by Christoph Thurm, Annegret Reinhold, Katrin Borucki, Sascha Kahlfuss, Eugen Feist, Jens Schreiber, Dirk Reinhold and Burkhart Schraven

Vaccines 2022, 10(2), 333; https://doi.org/10.3390/vaccines10020333 - 18 Feb 2022

Cited by 17 | Viewed by 3917

Abstract

The COVID-19 pandemics has caused the death of almost six million people worldwide. In order to establish collective immunity, the first vaccines that were approved in Germany were the vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, respectively. As it [...] Read more.

The COVID-19 pandemics has caused the death of almost six million people worldwide. In order to establish collective immunity, the first vaccines that were approved in Germany were the vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, respectively. As it was reported that SARS-CoV-2 can trigger autoimmunity, it is of significant interest to investigate whether COVID-19 vaccines evoke the formation of autoantibodies and subsequent autoimmunity. Here, we analyzed immune responses after different vaccination regimens (mRNA/mRNA, Vector/Vector or Vector/mRNA) with respect to anti-SARS-CoV-2-specific immunity and the development of autoantibodies well known for their appearance in distinct autoimmune diseases. We found that anti-SARS-CoV-2 antibody levels were 90% lower after Vector/Vector vaccination compared to the other vaccinations and that Vector/mRNA vaccination was more effective than mRNA/mRNA vaccination in terms of IgM and IgA responses. However, until 4 months after booster vaccination we only detected increases in autoantibodies in participants with already pre-existing autoantibodies whereas vaccinees showing no autoantibody formation before vaccination did not respond with sustained autoantibody production. Taken together, our study suggests that all used COVID-19 vaccines do not significantly foster the appearance of autoantibodies commonly associated with lupus erythematodes, rheumatoid arthritis, Celiac disease and antiphospholipid-syndrome but provide immunity to SARS-CoV-2. Full article

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Homologous and heterologous prime-boost immunization regimens induce anti-SARS-CoV-2 antibody production and immunity. (A) Study design and sample generation. Based on the received vaccinations, participants were grouped into the mRNA/mRNA, Vector/Vector or Vector/mRNA group. Serum samples were obtained one day before as well as 14, 28 and 120 days after booster. (B) Serum levels of anti-SARS-CoV-2-Sp1-IgG antibodies after vector (blue) or mRNA (red) prime one day before booster vaccination. The dashed line indicates the applied cutoff for positivity. (C) Left: Profile of serum anti-SARS-CoV-2-Sp1-IgG antibodies of individual participants based on the different vaccination strategies (red-mRNA/mRNA; blue-Vector/Vector; green-mRNA/Vector). Connected circles represent antibody levels of individual participants. Right: Serum anti-SARS-CoV-2-Sp1-IgG antibodies according to the study groups at the different time points. (D) Left: Profile of serum anti-SARS-CoV-2-Sp1 antibodies of individual participants based on the different vaccination strategies and indicated groups. Connected circles represent antibody levels for individual participants. Right: Serum anti-SARS-CoV-2-Sp1 antibodies according to the study groups at the different time points. (E) Levels of neutralizing antibodies after Vector (blue) or mRNA (red) prime one day before booster vaccination. (F) Left: Profile of neutralizing antibodies of individual participants within the indicated groups. Connected circles represent the antibody levels of an individual participant. Right: Neutralizing antibodies according to the study groups at the different time points. (F) IFN-γ release upon stimulation with SARS-CoV-2 peptides four months post booster vaccination (red-mRNA/mRNA, blue-Vector/Vector, green-mRNA/Vector). Outliers have been identified by ROUT method and excluded from statistical analysis. Statistical analyses: Mann–Whitney test (B,E), Mixed-effects analysis with Tukey’s multiple comparison test within and between groups (C,D,F) and Kruskal–Wallis test (G). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Full article ">Figure 2
Reactogenicity after prime vaccinations with an mRNA or Vector vaccine and after booster vaccination for the mRNA/mRNA, Vector/Vector (V/V) and Vector/mRNA (V/mRNA) groups. (A) Analysis of local and systemic reactions; (B) analysis of the severity of reactions based on the number of symptoms; (C) analysis of the frequencies of local reactions; (D) analysis of the frequencies of systemic reactions. Full article ">Figure 3
Analysis of autoantibody levels in the serum of the participants at the different time points and in the different groups (red-mRNA/mRNA; blue-Vector/Vector; green-Vector/mRNA). Connected circles represent the antibody levels of an individual participant. (A) anti-Cardiolipin; (B) anti-Prothrombin; (C) anti-β2-Glycoprotein; (D) anti-CCP; (E) anti-TTG autoantibody levels in the indicated groups. (F) Analysis of ANAs in serum samples of the shown groups. Color of the boxes indicate individual titers and numbers state the respective patterns. Statistical analyses by Mixed-effects analysis with Tukey’s multiple comparison test within and between groups (C). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Full article ">

16 pages, 1300 KiB

Open AccessArticle

Propensity-Score-Matched Evaluation of Adverse Events Affecting Recovery after COVID-19 Vaccination: On Adenovirus and mRNA Vaccines

by Chang-Sik Son, Sang-Hyeon Jin and Won-Seok Kang

Vaccines 2022, 10(2), 284; https://doi.org/10.3390/vaccines10020284 - 13 Feb 2022

Cited by 5 | Viewed by 3284

Abstract

This study aimed to observe adverse events following immunisation (AEFIs) that affected recovery within two weeks after COVID-19 vaccination and investigate their risks in propensity-score-matched populations. Data were collected from 447,346 reports from the VAERS between 1 January 2021 and 31 July 2021. [...] Read more.

This study aimed to observe adverse events following immunisation (AEFIs) that affected recovery within two weeks after COVID-19 vaccination and investigate their risks in propensity-score-matched populations. Data were collected from 447,346 reports from the VAERS between 1 January 2021 and 31 July 2021. Propensity-score-matched populations were constructed by adjusting for demographic characteristics and 11 underlying diseases in eligible subjects who received 1 of 3 COVID-19 vaccines: 19,462 Ad26.COV2.S, 120,580 mRNA-1273, and 100,752 BNT162b2. We observed that 88 suspected AEFIs (22 in Ad26.COV2.S, 62 in mRNA-1273, and 54 in BNT162b2) were associated with an increased risk of delayed recovery within 2 weeks after COVID-19 vaccinations. Nervous system, musculoskeletal and connective tissue, gastrointestinal, skin, and subcutaneous tissue disorders were the most common AEFIs after COVID-19 vaccination. Interestingly, four local and systemic reactions affected recovery in different vaccine recipients during our study period: asthenic conditions and febrile disorders in Ad26.COV2.S and mRNA-1273; general signs and symptoms in mRNA-1273 and BNT162b2; injection site reactions in Ad26.COV2.S and BNT162b2. Although it is necessary to confirm a causal relationship with COVID-19 vaccinations, some symptoms, including paralysis, allergic disorders, breathing abnormalities, and visual impairment, may hinder the recovery of these recipients. Full article

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10 pages, 1232 KiB

Open AccessArticle

Antibody Response of Combination of BNT162b2 and CoronaVac Platforms of COVID-19 Vaccines against Omicron Variant

by Ka-Wa Khong, Danlei Liu, Ka-Yi Leung, Lu Lu, Hoi-Yan Lam, Linlei Chen, Pui-Chun Chan, Ho-Ming Lam, Xiaochun Xie, Ruiqi Zhang, Yujing Fan, Kelvin Kai-Wang To, Honglin Chen, Kwok-Yung Yuen, Kwok-Hung Chan and Ivan Fan-Ngai Hung

Vaccines 2022, 10(2), 160; https://doi.org/10.3390/vaccines10020160 - 21 Jan 2022

Cited by 35 | Viewed by 6188

Abstract

By vaccinating SARS-CoV-2 naïve individuals who have already received two doses of COVID-19 vaccines, we aimed to investigate whether a heterologous prime-boost strategy, using vaccines of different platforms as the booster dose, can enhance the immune response against SARS-CoV-2 virus variants. Participants were [...] Read more.

By vaccinating SARS-CoV-2 naïve individuals who have already received two doses of COVID-19 vaccines, we aimed to investigate whether a heterologous prime-boost strategy, using vaccines of different platforms as the booster dose, can enhance the immune response against SARS-CoV-2 virus variants. Participants were assigned into four groups, each receiving different combination of vaccinations: two doses of BNT162b2 followed by one dose of BNT162b2 booster (B-B-B); Combination of BNT162b2 (first dose) and CoronaVac (second dose) followed by one dose of BNT162b2 booster (B-C-B); two doses of CoronaVac followed by one dose of CoronaVac booster (C-C-C); two doses of CoronaVac followed by one dose of BNT162b2 booster (C-C-B). The neutralizing antibody in sera against the virus was determined with live virus microneutralization assay (vMN). The B-B-B group and C-C-B group demonstrated significantly higher immunogenicity against SARS-CoV-2 Wild type (WT), Beta variant (BV) and Delta variant (DV). In addition, the B-B-B group and C-C-B group showed reduced but existing protection against Omicron variant (OV). Moreover, A persistent rise in vMN titre against OV was observed 3 days after booster dose. Regarding safety, a heterologous prime-boost vaccine strategy is well tolerated. In this study, it was demonstrated that using vaccines of different platforms as booster dose can enhance protection against SARS-CoV-2 variants, offering potent neutralizing activity against wild-type virus (WT), Beta variant (BV), Delta variant (DV) and some protection against the Omicron variant (OV). In addition, a booster mRNA vaccine results in a more potent immune response than inactivated vaccine regardless of which platform was used for prime doses. Full article

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8 pages, 767 KiB

Open AccessArticle

The Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Japanese Patients after Allogeneic Stem Cell Transplantation

by Marika Watanabe, Kimikazu Yakushijin, Yohei Funakoshi, Goh Ohji, Wataru Hojo, Hironori Sakai, Miki Saeki, Yuri Hirakawa, Sakuya Matsumoto, Rina Sakai, Shigeki Nagao, Akihito Kitao, Yoshiharu Miyata, Taiji Koyama, Yasuyuki Saito, Shinichiro Kawamoto, Mitsuhiro Ito, Tohru Murayama, Hiroshi Matsuoka and Hironobu Minami

Vaccines 2022, 10(2), 158; https://doi.org/10.3390/vaccines10020158 - 21 Jan 2022

Cited by 16 | Viewed by 3260

Abstract

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety [...] Read more.

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) had seroconversion of anti-S1 IgG. The median optical density of antibody levels in HSCT patients with low IgG levels (<600 mg/dL), steroid treatment, or low lymphocytes (<1000/μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (>Grade 3) and no new development or exacerbation of graft-versus-host disease after vaccination. We concluded that the BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients. Full article

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10 pages, 906 KiB

Open AccessArticle

The Association of Previous Vaccination with Live-Attenuated Varicella Zoster Vaccine and COVID-19 Positivity: An Israeli Population-Based Study

by Eugene Merzon, Ilan Green, Eli Somekh, Shlomo Vinker, Avivit Golan-Cohen, Ariel Israel, Alessandro Gorohovski, Milana Frenkel-Morgenstern and Michal Stein

Vaccines 2022, 10(1), 74; https://doi.org/10.3390/vaccines10010074 - 4 Jan 2022

Cited by 4 | Viewed by 3120

Abstract

The Bacillus Calmette–Guérin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. [...] Read more.

The Bacillus Calmette–Guérin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. A retrospective population-based cross-sectional study was conducted using the Leumit Health Services (LHS) database. LAVZ-vaccinated patients were matched with controls based on a propensity score model using 1:9 nearest-neighbor matching. Matching was based on age, gender, and the presence of some chronic disorders, which were selected according to their association with COVID-19 infection. Multivariate logistic regression analyses, adjusted for sex, age, smoking status, comorbidities, and chronic medications associated with COVID-19 risk, were used to estimate the association between LAVZ vaccination and COVID-19 RT-PCR results. Subjects (625) vaccinated with LAVZ and RT-PCR-tested for COVID-19 were identified. After 1:9 matching of subjects who received the LAVZ vaccine, 6250 subjects were included in the study. Multivariate logistic regression analysis demonstrated a significant and independent negative association between having received the LAVZ vaccine and the likelihood of COVID-19 infection (adjusted OR = 0.47 (95% CI 0.33–0.69, p < 0.001)). This association was further strengthened after separate analysis based on the time of LAVZ vaccination before COVID-19 RT-PCR testing. Individuals aged ≥50 years vaccinated with LAVZ had a decreased likelihood of being tested positive for COVID-19. Full article

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2021

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12 pages, 1459 KiB

Open AccessArticle

Antibody Response of BNT162b2 and CoronaVac Platforms in Recovered Individuals Previously Infected by COVID-19 against SARS-CoV-2 Wild Type and Delta Variant

by Ruiqi Zhang, Ka-Wa Khong, Ka-Yi Leung, Danlei Liu, Yujing Fan, Lu Lu, Pui-Chun Chan, Linlei Chen, Kelvin Kai-Wang To, Honglin Chen, Kwok-Yung Yuen, Kwok-Hung Chan and Ivan Fan-Ngai Hung

Vaccines 2021, 9(12), 1442; https://doi.org/10.3390/vaccines9121442 - 7 Dec 2021

Cited by 19 | Viewed by 4541

Abstract

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected [...] Read more.

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected by COVID-19 were recruited and received one booster dose of the BNT162b2 (PC-B) or CoronaVac (PC-C) vaccines, while SARS-CoV-2 naïve subjects received two doses of the BNT162b2 (CN-B) or CoronaVac (CN-C) vaccines. The neutralizing antibody in sera against the WT and DV was determined with live virus neutralization assay (vMN). The vMN geometric mean titre (GMT) against WT in recovered individuals previously infected by COVID-19 reduced significantly from 60.0 (95% confidence interval (CI), 46.5–77.4) to 33.9 (95% CI, 26.3–43.7) at 6 months post recovery. In the PC-B group, the BNT162b2 vaccine enhanced antibody response against WT and DV, with 22.3-fold and 20.4-fold increases, respectively. The PC-C group also showed 1.8-fold and 2.2-fold increases for WT and DV, respectively, after receiving the CoronaVac vaccine. There was a 10.6-fold increase in GMT in the CN-B group and a 1.3-fold increase in the CN-C group against DV after full vaccination. In both the PC-B and PC-C groups, there was no difference between GMT against WT and DV after vaccination. Subjects in the CN-B and CN-C groups showed inferior GMT against DV compared with GMT against WT after vaccination. In this study, one booster shot effectively enhanced the pre-existing neutralizing activity against WT and DV in recovered subjects. Full article

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Trial profile. Full article ">Figure 2
Change in neutralizing activity in participants after recovering from COVID-19. Convalescent patients infected by COVID-19 aged above 18 years were recruited, and blood samples were taken after discharge and at 6 weeks, 12 weeks, 6 months, and 1 year post recovery. vMN was used to determine the neutralizing antibody in sera. BL: baseline; W6: 6 weeks post recovery; W12: 12 weeks post recovery; M6: 6 months post recovery; Y1: 1 year post recovery; p < 0.05, statistically significant difference. Each dot represents an individual serum sample, and the error bar represents the 95% confidential interval (CI). Full article ">Figure 3
GMT fold change after vaccination. (a) Recovered individuals previously infected by COVID-19 received a booster dose of BNT162b2 (PC-B) or CoronaVac (PC-C) and had their blood taken at baseline and at day 28 post vaccination. SARS-CoV-2 naïve participants received two doses of BNT 162b2 (CN-B) or CoronaVac (CN-C) and has their blood collected at baseline, on day 21 (CN-B) and day 28 (CN-C), and on day 56 after their first dose. Neutralizing antibody titre in serum was determined with vMN, and GMT change against the wild type (b) and Delta variant (c) was determined by comparing the antibody titre after vaccination with the antibody titre at baseline. PFD: post first dose; PSD: post second dose. Full article ">Figure 4
Comparison of neutralizing antibody titre against wild type and Delta variant after vaccination. Recovered individuals previously infected by COVID-19 received a booster of BNT162b2 (PC-B) or CoronaVac vaccines (PC-C) and had their blood taken at baseline and day 28 post vaccination. SARS-CoV-2 naïve participants received two doses of BNT 162b2 (CN-B) or CoronaVac (CN-C) and had their blood collected at baseline, on day 21 (CN-B) or day 28 (CN-C), and on day 56 after their first dose. vMN was used to determine neutralizing antibody titre in sera from (a) PC-B, (b) PC-C, (c) CN-B, and (d) CN-C. WT: wild type; DV: Delta variant; BL: baseline; PFD: post first dose; PSD: post second dose. Full article ">

12 pages, 2210 KiB

Open AccessArticle

Unfolding the Mild to Moderate Short-Term Side Effects of Four COVID-19 Vaccines Used in Bahrain: A Cross-Sectional Study

by Muhammad Nauman Zahid

Vaccines 2021, 9(11), 1369; https://doi.org/10.3390/vaccines9111369 - 22 Nov 2021

Cited by 21 | Viewed by 4574

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) created a global pandemic (COVID-19) that has resulted in massive health and economic losses. The current unavailability of treatments leaves vaccination as the only way to control this disease. There are four vaccines (Sinopharm, Pfizer—BioNTech, Sputnik, [...] Read more.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) created a global pandemic (COVID-19) that has resulted in massive health and economic losses. The current unavailability of treatments leaves vaccination as the only way to control this disease. There are four vaccines (Sinopharm, Pfizer—BioNTech, Sputnik, and AstraZeneca) available in Bahrain. This project aimed to study the most common side effects resulting from the first and second doses of these four vaccines. Data were collected through an online questionnaire answered by 311 individuals who received both doses of one of these four vaccines. The results of this study revealed that regardless of the vaccine identity, participants experienced more side effects from the second dose. Among the different side effects, pain at the site of injection was primarily observed after the first dose of the Pfizer vaccine (43%), which was followed by the AstraZeneca vaccine (31%). Moreover, fever was observed in participants after the first dose of the Sputnik vaccine (37%), while headache was mainly observed after the first dose of the Pfizer vaccine (32%). It is important to note that fatigue was observed after the first dose of all four vaccines but was reported by the highest proportion of respondents in the Pfizer group (28%). Interestingly, there are some side effects, such as pain at the site of injection, that are correlated with fever (r = 0.909). Similarly, headache is correlated with fever (r = 0.801) and pain at the site of injection (r = 0.868). Overall, it was observed that recipients of the Sinopharm vaccine reported the mildest side effects among all four vaccines. The crucial finding of this study is that the first and second dosage post-vaccination side effects were modest and predictable with no occurrences of hospitalization; this information can assist in lessening vaccine apprehension. Full article

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Pain at the Injection Site. Estimated marginal means of pain at the site of injection after the first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 2
Fever. Estimated marginal means of fever after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 3
Headache. Estimated marginal means of headache after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 4
Myalgia. Estimated marginal means of myalgia after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 5
Nausea. Estimated marginal means of nausea after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 6
Cough. Estimated marginal means of cough after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 7
Fatigue. Estimated marginal means of fatigue after first and second doses of vaccines used in the Kingdom of Bahrain. Full article ">Figure 8
Pearson’s heatmap. Pearson’s heatmap illustrates the correlation among different side effects of COVID-19 vaccines that have been used in the Kingdom of Bahrain. * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">

11 pages, 272 KiB

Open AccessArticle

COVID-19 Vaccine Boosters: The Good, the Bad, and the Ugly

by Piotr Rzymski, Carlos A. Camargo, Jr., Andrzej Fal, Robert Flisiak, Willis Gwenzi, Roya Kelishadi, Alexander Leemans, Juan J. Nieto, Ahmet Ozen, Matjaž Perc, Barbara Poniedziałek, Constantine Sedikides, Frank Sellke, Emilia C. Skirmuntt, Anzhela Stashchak and Nima Rezaei

Vaccines 2021, 9(11), 1299; https://doi.org/10.3390/vaccines9111299 - 9 Nov 2021

Cited by 67 | Viewed by 12484

Abstract

Pursuing vaccinations against COVID-19 brings hope to limit the spread of SARS-CoV-2 and remains the most rational decision under pandemic conditions. However, it does not come without challenges, including temporary shortages in vaccine doses, significant vaccine inequity, and questions regarding the durability of [...] Read more.

Pursuing vaccinations against COVID-19 brings hope to limit the spread of SARS-CoV-2 and remains the most rational decision under pandemic conditions. However, it does not come without challenges, including temporary shortages in vaccine doses, significant vaccine inequity, and questions regarding the durability of vaccine-induced immunity that remain unanswered. Moreover, SARS-CoV-2 has undergone evolution with the emergence of its novel variants, characterized by enhanced transmissibility and ability to at least partially evade neutralizing antibodies. At the same time, serum antibody levels start to wane within a few months after vaccination, ultimately increasing the risk of breakthrough infections. This article discusses whether the administration of booster doses of COVID-19 vaccines is urgently needed to control the pandemic. We conclude that, at present, optimizing the immunity level of wealthy populations cannot come at the expense of low-income regions that suffer from vaccine unavailability. Although the efficiency of vaccination in protecting from infection may decrease over time, current data show that efficacy against severe disease, hospitalization, and death remains at a high level. If vaccine coverage continues at extremely low levels in various regions, including African countries, SARS-CoV-2 may sooner or later evolve into variants better adapted to evade natural and vaccine-induced immunity, ultimately bringing a global threat that, of course, includes wealthy populations. We offer key recommendations to increase vaccination rates in low-income countries. The pandemic is, by definition, a major epidemiological event and requires looking beyond one’s immediate self-interest; otherwise, efforts to contain it will be futile. Full article

10 pages, 782 KiB

Open AccessArticle

Humoral Response after Vaccination with Half-Dose of BNT162b2 in Subjects under 55 Years of Age

by Krzysztof Lukaszuk, Amira Podolak, Grzegorz Jakiel, Jolanta Kiewisz, Izabela Woclawek-Potocka, Aron Lukaszuk and Lukasz Rabalski

Vaccines 2021, 9(11), 1277; https://doi.org/10.3390/vaccines9111277 - 4 Nov 2021

Cited by 1 | Viewed by 3880

Abstract

In the context of the ongoing COVID-19 pandemic, using a half-dose schedule vaccination can help to return to normalcy in a cost-efficient manner, which is especially important for low and middle-income countries. We undertook a study to confirm that in adults up to [...] Read more.

In the context of the ongoing COVID-19 pandemic, using a half-dose schedule vaccination can help to return to normalcy in a cost-efficient manner, which is especially important for low and middle-income countries. We undertook a study to confirm that in adults up to 55 years old, the humoral response to the half-dose (15 µg, 35 participants between 18 and 55 years old) and to the recommended dose (30 µg, 155 participants) in the two-dose three-week interval schedule would be comparable. Antibody levels were measured by the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics, upper detection limit: 2570 BAU/mL) on the day of dose 2 of the vaccine and then 8–10 days later to assess peak response to dose 2. The difference in proportions between the participants who did and did not exceed the upper detection limit 8–10 days after dose 2 was not statistically significant (p = 0.152). We suggest that a half-dose schedule can help to achieve widespread vaccination coverage more quickly and cheaply. Full article

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8 pages, 455 KiB

Open AccessCommunication

Assessment of Anti-SARS-CoV-2 Antibodies Post-Coronavac Vaccination in the Amazon Region of Brazil

by Carlos David Araújo Bichara, Maria Alice Freitas Queiroz, Ednelza da Silva Graça Amoras, Gergiane Lopes Vaz, Izaura Maria Vieira Cayres Vallinoto, Cléa Nazaré Carneiro Bichara, Isabella Pinheiro Costa do Amaral, Ricardo Ishak and Antonio Carlos Rosário Vallinoto

Vaccines 2021, 9(10), 1169; https://doi.org/10.3390/vaccines9101169 - 12 Oct 2021

Cited by 12 | Viewed by 3010

Abstract

The present study evaluated the frequency of seropositivity for anti-SARS-CoV-2 (S1 and S2) total antibodies and anti-SARS-CoV-2 (receptor binding domain-RBD-S1) neutralizing antibodies in individuals vaccinated with the immunizing agent Coronavac. This was a cross-sectional study involving 358 individuals divided into two groups. Group [...] Read more.

The present study evaluated the frequency of seropositivity for anti-SARS-CoV-2 (S1 and S2) total antibodies and anti-SARS-CoV-2 (receptor binding domain-RBD-S1) neutralizing antibodies in individuals vaccinated with the immunizing agent Coronavac. This was a cross-sectional study involving 358 individuals divided into two groups. Group 1 consisted of 205 volunteers who were tested for anti-SARS-CoV-2 total antibodies; group 2 consisted of 153 individuals tested for the presence of anti-SARS-CoV-2 neutralizing antibodies. Seropositivity was greater than 70% in both groups, although 17.6% and 20.9% of individuals showed no neutralizing or total antibody reactivity, respectively. The frequency of anti-SARS-CoV-2 total antibodies displayed a significantly different distribution between the sexes but not according to age. The frequency of anti-SARS-CoV-2 neutralizing antibodies was 93.3% (95% CI 68.1–99.8) in the age group from 21 to 40 years but significantly decreased with advancing age, and was 76.2% (95% CI 52.8–91.8) for 41 to 60 years, 72.5% (95% CI 62.8–80.9) for 61 to 80 years, and 46.7% (95% CI 21.3–73.4) for >80 years. Our results reveal a high prevalence of anti-SARS-CoV-2 total antibodies and anti-SARS-CoV-2 neutralizing antibodies in individuals who received both doses of the Coronavac vaccine, suggesting a lower effectiveness of the humoral immune response among those older than 60 years of age, which might be associated with senescence of the immune system. Full article

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8 pages, 838 KiB

Open AccessArticle

Immunological Response to COVID-19 Vaccination in Ovarian Cancer Patients Receiving PARP Inhibitors

by Michalis Liontos, Evangelos Terpos, Christos Markellos, Flora Zagouri, Alexandros Briasoulis, Ioanna Katsiana, Efthymia Skafida, Oraianthi Fiste, Elena Kunadis, Angeliki Andrikopoulou, Maria Kaparelou, Konstantinos Koutsoukos, Maria Gavriatopoulou, Efstathios Kastritis, Ioannis P. Trougakos and Meletios-Athanasios Dimopoulos

Vaccines 2021, 9(10), 1148; https://doi.org/10.3390/vaccines9101148 - 8 Oct 2021

Cited by 10 | Viewed by 4676

Abstract

Objective: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy. Methods: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order [...] Read more.

Objective: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy. Methods: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order to study the kinetics of anti-SARS-CoV-2 antibodies (NAbs) after COVID-19 vaccination. Baseline demographics, co-morbidities, and NAb levels were compared between the two groups. Results: The results of the cohort of 36 patients receiving PARP inhibitors are presented here. Despite no new safety issues being noticed, their levels of SARS-CoV-2 neutralizing antibodies were significantly lower in comparison to matched healthy volunteers up to day 30 after the second dose. Conclusions: These results suggest that maintaining precautions against COVID-19 is essential for cancer patients and should be taken into consideration for the patients under treatment, while further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment. Full article

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10 pages, 1370 KiB

Open AccessArticle

Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

by Sara Caucci, Benedetta Corvaro, Sofia Maria Luigia Tiano, Anna Valenza, Roberta Longo, Katia Marinelli, Monica Lucia Ferreri, Patrik Spiridigliozzi, Giovanna Salvoni, Patrizia Bagnarelli and Stefano Menzo

Vaccines 2021, 9(10), 1124; https://doi.org/10.3390/vaccines9101124 - 2 Oct 2021

Cited by 3 | Viewed by 3691

Abstract

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine [...] Read more.

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response. Full article

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15 pages, 2628 KiB

Open AccessArticle

Neutralizing Antibodies against SARS-CoV-2, Anti-Ad5 Antibodies, and Reactogenicity in Response to Ad5-nCoV (CanSino Biologics) Vaccine in Individuals with and without Prior SARS-CoV-2

by Jorge Hernández-Bello, José Javier Morales-Núñez, Andrea Carolina Machado-Sulbarán, Saúl Alberto Díaz-Pérez, Paola Carolina Torres-Hernández, Paulina Balcázar-Félix, Jesús Alberto Gutiérrez-Brito, José Alvaro Lomelí-Nieto and José Francisco Muñoz-Valle

Vaccines 2021, 9(9), 1047; https://doi.org/10.3390/vaccines9091047 - 20 Sep 2021

Cited by 21 | Viewed by 8744

Abstract

This is the first study outside of clinical trials (phase I–III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 [...] Read more.

This is the first study outside of clinical trials (phase I–III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 without prior COVID-19) vaccinated with Ad5-nCoV were recruited. The percentage of neutralizing antibodies against SARS-CoV-2 (Surrogate Virus Neutralization Test) and antibodies against Ad5 (ADV-Ad5 IgG ELISA) were quantified pre and post-vaccination effects. The Ad5-nCoV vaccine induces higher neutralizing antibodies percentage in individuals with prior COVID-19 than those without prior COVID-19 (median [IQR]: 98% [97–98.1] vs. 72% [54–90], respectively; p < 0.0001). Furthermore, a natural infection (before vaccination) induces more neutralizing antibodies percentage than immunized individuals without prior COVID-19 (p < 0.01). No patient had vaccine-severe adverse effects. The age, antidepressant, and immunosuppressive treatments, reactogenicity, and history of COVID-19 are associated with impaired antibody production. The anti-Ad5 antibodies increased after 21 days of post-vaccination in all groups (p < 0.01). We recommend the application of a booster dose of Ad5-nCoV, especially for those individuals without previous COVID-19 infection. Finally, the induction of anti-Ad5 antibodies after vaccination should be considered if a booster with the same vaccine is planned. Full article

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Figure 1
Percentage of neutralizing signal of antibodies generated in response to the Ad5-nCoV vaccine. (A) Individuals without prior COVID-19; (B) individuals with prior COVID-19. Differences were calculated by the Wilcoxon signed-rank test. The dotted line indicates the cut-off point for the neutralization test (>30%). The “basal” status represents the neutralization percentage before the effect of vaccination (3 days after vaccination). Full article ">Figure 2
Comparison of the neutralization percentages of the antibodies generated in response to the Ad5-nCoV vaccine. The difference between all groups was calculated with the U-Mann–Whitney test or the Wilcoxon signed-rank test. The data are provided as medians and interquartile ranges. ****, p < 0.0001; **, p < 0.001. Full article ">Figure 3
Relationship between prior COVID-19 clinical course and days after infection with the percentage of neutralization. (A) Comparison of basal neutralization percentage between individuals with different prior COVID-19 clinical courses; (B) comparison of neutralization percentage after 21 days of immunization with the Ad5-nCoV vaccine among individuals with different prior COVID-19 clinical courses. Correlation between percentage of neutralization and the time of a previous COVID-19 infection: (C) Basal neutralization percentage, and (D) neutralization percentage after 21 days of the vaccination. The difference between all groups was calculated with the Kruskal–Wallis test, followed by the U-Mann–Whitney test. Data are provided as median and interquartile ranges. Full article ">Figure 4
Correlation between the age and neutralization percentage. (A) After 21 days of vaccination in patients without prior COVID-19; (B) in basal status in patients with prior COVID-19; (C) after 21 days of vaccination in patients with prior COVID-19. Analysis was evaluated by the Spearman’s rank correlation coefficient. Full article ">Figure 5
Anti-Ad5 antibodies and percentage of neutralization. Correlation between anti-Ad5 antibodies and percentage of neutralization of anti-SARS-CoV-2 antibodies: (A) after 21 days of vaccination in patients without prior COVID-19, (B) in basal status in patients with prior COVID-19, and (C) after 21 days of vaccination in patients with prior COVID-19. Levels of anti-Ad5 antibodies generated in response to the Ad5-nCoV vaccine in individuals without (D) and with (E) prior COVID-19. Full article ">

12 pages, 2690 KiB

Open AccessArticle

Immunological Analysis of People in Northeast China after SARS-CoV-2 Inactivated Vaccine Injection

by Yu Fu, Fang Chen, Lifen Cui, Yue Zhao, Henan Zhang, Shuang Fu and Jihong Zhang

Vaccines 2021, 9(9), 1028; https://doi.org/10.3390/vaccines9091028 - 16 Sep 2021

Cited by 11 | Viewed by 3468

Abstract

Clarifying changes in the immune microenvironment caused by vaccination is crucial for the development and application of vaccines. In this study, we analyzed seroconversion of antibodies, 12 key cytokines, and 34 lymphocyte subsets at three time points (D-1, D14, and D42) around vaccination [...] Read more.

Clarifying changes in the immune microenvironment caused by vaccination is crucial for the development and application of vaccines. In this study, we analyzed seroconversion of antibodies, 12 key cytokines, and 34 lymphocyte subsets at three time points (D-1, D14, and D42) around vaccination and differences between two inactivated vaccines (Sinopharm and Sinovas) to understand the immune response induced by inactivated vaccines in the real world. The results showed that 62.5% and 75% of the participants achieved neutralizing antibody seroconversion on D14 and D42, respectively. After vaccination, IL-5 and IL-6 increased, and INF-γ decreased. IL6, IL-1B, INF-γ, IL-8, and IL-12p70 showed statistical significance in the comparison of different groups. In terms of lymphocyte subsets, CD3 +, CD56 +, CD3 + CD8 +, CD8 + CD71 +, and CD56 + CD71 + showed upward trend, while CD19 +, CD4 + CD8 +, CD8 + CD45RA +, CD4 + HLA-DR +, CD8 + HLA-DR +, and CD8 + CD38 + showed downward trend. Additionally, we found certain differences between the two vaccines in neutralizing antibodies, cytokines, and lymphocyte subsets. This research is a clinical observation on the immune response after vaccination through detecting various immune indicators, which showed that the inactivated vaccines induced both humoral immunity by producing neutralizing antibodies and cellular immunity. The cellular immunity induced by these two vaccines was a Th2-biased response, and it may also lead to a mild Th1-type response. Full article

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8 pages, 233 KiB

Open AccessBrief Report

Increased Risk of Urticaria/Angioedema after BNT162b2 mRNA COVID-19 Vaccine in Health Care Workers Taking ACE Inhibitors

by Massimo Cugno, Dario Consonni, Andrea Lombardi, Patrizia Bono, Massimo Oggioni, Sara Uceda Renteria, Angela Cecilia Pesatori, Silvana Castaldi, Luciano Riboldi, Lorenzo Bordini, Carlo Domenico Nava, Ferruccio Ceriotti, Adriana Torri, Francesco Tafuri, Gabriele Ghigliazza, Flora Peyvandi, Alessandra Bandera and Andrea Gori

Vaccines 2021, 9(9), 1011; https://doi.org/10.3390/vaccines9091011 - 11 Sep 2021

Cited by 11 | Viewed by 5345

Abstract

Urticarial eruptions and angioedema are the most common cutaneous reactions in patients undergoing mRNA COVID-19 vaccinations. The vasoactive peptide bradykinin has long been known to be involved in angioedema and recently also in urticaria. Bradykinin is mainly catabolized by angiotensin-converting enzyme (ACE), which [...] Read more.

Urticarial eruptions and angioedema are the most common cutaneous reactions in patients undergoing mRNA COVID-19 vaccinations. The vasoactive peptide bradykinin has long been known to be involved in angioedema and recently also in urticaria. Bradykinin is mainly catabolized by angiotensin-converting enzyme (ACE), which is inhibited by ACE inhibitors, a commonly employed class of antihypertensive drugs. We evaluated the risk of developing urticaria/angioedema after inoculation with the BNT162b2 mRNA COVID-19 vaccine in a population of 3586 health care workers. The influences of ACE inhibitors and selected potential confounding variables (sex, age, previous SARS-CoV-2 infection, and allergy history) were evaluated by fitting univariate and multivariable Poisson regression models. The overall cumulative incidence of urticaria/angioedema was 1.8% (65 out of 3586; 95% CI: 1.4–2.3%). Symptoms were mild, and no subject consulted a physician. Subjects taking ACE inhibitors had an adjusted three-fold increased risk of urticaria/angioedema (RR 2.98, 95% CI: 1.12–7.96). When we restricted the analysis to those aged 50 years or more, the adjusted RR was 3.98 (95% CI: 1.44–11.0). In conclusion, our data indicate that subjects taking ACE inhibitors have an increased risk of urticaria/angioedema after vaccination with the BNT162b2 mRNA COVID-19 vaccine. Symptoms are mild and self-limited; however, they should be considered to adequately advise subjects undergoing vaccination. Full article

6 pages, 915 KiB

Open AccessCase Report

Intradermal ChAdOx1 Vaccine Following Two CoronaVac Shots: A Case Report

by Ekachai Singhatiraj, Krit Pongpirul, Anan Jongkaewwattana and Nattiya Hirankarn

Vaccines 2021, 9(9), 990; https://doi.org/10.3390/vaccines9090990 - 4 Sep 2021

Cited by 6 | Viewed by 6729

Abstract

Inactivated SARS-CoV-2 vaccines are used in many countries with uncertain immunogenicity. Intradermal ChAdOx1 has been proposed as a resource-efficient heterologous third booster shot. A 52-year-old healthy male healthcare professional had received two intramuscular CoronaVac shots on 21 April and 23 May 2021, and [...] Read more.

Inactivated SARS-CoV-2 vaccines are used in many countries with uncertain immunogenicity. Intradermal ChAdOx1 has been proposed as a resource-efficient heterologous third booster shot. A 52-year-old healthy male healthcare professional had received two intramuscular CoronaVac shots on 21 April and 23 May 2021, and volunteered to take a 0.1 mL ChAdOx1 vaccine intradermally on 29 June 2021, with minimal local reactions. The declining IgG levels against spike protein from the two CoronaVac shots increased to higher than 10,000 AU/mL two weeks after the intradermal ChAdOx1. Moreover, the neutralizing antibody increased from 66.77% to almost 100%. A ratio of 6.6:9.7 of IgA:IgG was observed. The 50% pseudovirus neutralization titer (PVNT50) against lentiviral pseudovirus bearing a codon-optimized spike gene (wild type, alpha, beta, and delta) were 1812.42, 822.99, 1025.42, 1347.13, respectively. The SARS-CoV-2-specific T cells to spike protein–peptide pools (532–788 SFU/10⁶ PBMCs) were detected. In conclusion, the antibody and cellular responses to the intradermal ChAdOx1, as a third booster dose in a healthy volunteer who received two intramuscular CoronaVac shots, revealed a dramatic increase in the total antibodies, including IgG, IgA, as well as T cell responses against spike protein. The immune response from intradermal ChAdOx1 should be further investigated in a larger population. Full article

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15 pages, 1311 KiB

Open AccessReview

Safety and Efficacy of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Different Vaccines at Phase 3

by Yu-Jing Fan, Kwok-Hung Chan and Ivan Fan-Ngai Hung

Vaccines 2021, 9(9), 989; https://doi.org/10.3390/vaccines9090989 - 4 Sep 2021

Cited by 83 | Viewed by 15258

Abstract

This systematic review and meta-analysis was conducted to compare the safety and efficacy of 2019 novel coronavirus disease (COVID-19) vaccines according to vaccine platform and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection severity. Articles published between 24 January 2020 and 30 May [...] Read more.

This systematic review and meta-analysis was conducted to compare the safety and efficacy of 2019 novel coronavirus disease (COVID-19) vaccines according to vaccine platform and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection severity. Articles published between 24 January 2020 and 30 May 2021 were retrieved via a PubMed and EMBASE search. A total of 12 reports on phase-3 clinical trials and observational studies of COVID-19 vaccines were included in the review. In terms of vaccine safety, mRNA vaccines showed more relevance to serious adverse events than viral vector and inactivated vaccines, but no solid evidence indicated that COVID-19 vaccines directly caused serious adverse events. Serious metabolic, musculoskeletal, immune-system, and renal disorders were more common among inactivated vaccine recipients, and serious gastrointestinal complications and infections were more common among viral vector and inactivated vaccine recipients. The occurrence of serious vessel disorders was more frequent in mRNA vaccines. In terms of efficacy, two mRNA vaccine doses conferred a lesser risk of SARS-COV-2 infection (odds ratio: 0.05; 95% confidence interval: 0.02–0.13) than did vaccination with viral vector and inactivated vaccines. All vaccines protected more against symptomatic than asymptomatic cases (risk ratio, 0.11 vs. 0.34), but reduced the risk of severe SARS-COV-2 infection. The COVID-19 vaccines assessed in this study are sufficiently safe and effective. The results indicate that two mRNA vaccine doses prevent SARS-COV-2 infection most effectively, but further research is needed due to the high degree of heterogeneity among studies in this sample. Interventions should be implemented continuously to reduce the risks of infection after one vaccine dose and asymptomatic infection. Full article

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14 pages, 3586 KiB

Open AccessArticle

COVID-19 Subunit Vaccine with a Combination of TLR1/2 and TLR3 Agonists Induces Robust and Protective Immunity

by Soo-Kyung Jeong, Yoon-Ki Heo, Jei-Hyun Jeong, Su-Jin Ham, Jung-Sun Yum, Byung-Cheol Ahn, Chang-Seon Song and Eun-Young Chun

Vaccines 2021, 9(9), 957; https://doi.org/10.3390/vaccines9090957 - 27 Aug 2021

Cited by 24 | Viewed by 4369

Abstract

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit [...] Read more.

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit vaccines to enhance the magnitude and durability of immune responses. In this study, we determined whether a combination of toll-like receptor (TLR)1/2 and TLR3 agonists (L-pampo) can be a potent adjuvant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. We measured a neutralizing antibody (nAb) and an angiotensin-converting enzyme 2 (ACE2) receptor-blocking antibody against SARS-CoV-2 receptor-binding domain (RBD). We also detected interferon-gamma (IFN-γ) production by using ELISPOT and ELISA assays. By employing a ferret model, we detected nAbs and IFN-γ producing cells and measured viral load in nasal wash after the challenge of SARS-CoV-2. We found that SARS-CoV-2 antigens with L-pampo stimulated robust humoral and cellular immune responses. The efficacy of L-pampo was higher than the other adjuvants. Furthermore, in the ferret model, SARS-CoV-2 antigens with L-pampo elicited nAb response and antigen-specific cellular immune response against SARS-CoV-2, resulting in substantially decreased viral load in their nasal wash. Our study suggests that SARS-CoV-2 antigens formulated with TLR agonists, L-pampo, can be a potent subunit vaccine to promote sufficient protective immunity against SARS-CoV-2. Full article

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Figure 1
Receptor-binding domain (RBD) and S1 antigens with L-pampo induce robust humoral responses. (A) A schematic of immunization strategy. BALB/c mice (total n = 48; n = 8/group) were immunized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens (RBD and S1) with or without adjuvants intramuscularly (i.m.) on day 0 and day 14. (B) Neutralizing antibody production on day 28. (C) Angiotensin-converting enzyme 2 (ACE2)-blocking antibody titers on day 28. (D) RBD-specific total IgG, IgG1, IgG2a, and IgG2b antibodies on day 28. Data shown are median ± Interquartile range (IQR). Each dot represents an individual mouse. GMT in antibody assay indicates geometric mean titers. Data reflect 2 independent experiments (n = 4/group in single experiment). Asterisks indicate statistically significant differences in comparison to the L-pampo (L) or L-pampo (H). * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ns, non-significant, one way ANOVA with the Tukey’s test. Full article ">Figure 2
RBD and S1 antigens with L-pampo induce strong cell-mediated responses. (A,B) BALB/c mice (total n = 48, n = 8/group in (A); total n = 42, n = 7/group in (B)) were immunized with SARS-CoV-2 antigens (RBD and S1) with or without adjuvants i.m. on day 0 and day 14 as described in <a href="#vaccines-09-00957-f001" class="html-fig">Figure 1</a>A. On day 28, splenocytes were stimulated with the PepMixTM SARS-CoV-2(S-RBD) peptide pool, and RBD-specific IFN-γ secreting cells were analyzed as spot-forming cells (SFCs) by ELISPOT assay (A) or total IFN-γ production by ELISA assay (B). Data shown are median ± IQR. Each dot represents an individual mouse. Data reflect 2 independent experiments (n = 4/group in single experiment). Asterisks indicate statistically significant differences in comparison to the L-pampo (L) or L-pampo (H) groups. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ns, non-significant, one way ANOVA with Tukey’s test. Full article ">Figure 3
RBD-Fc antigen with L-pampo induces robust humoral responses. (A) A schematic of the immunization strategy. BALB/c mice (total n = 42; n = 6/antigen-only; n = 8/Alum, AddaVax, AddaS03, or L-pampo (L); n = 4/CpG–Alum) were immunized with RBD-Fc with or without adjuvants i.m. on day 0 and day 21. (B) Neutralizing antibody production on day 35. (C) ACE2-blocking antibody titers on day 35. (D) Total RBD-specific IgG, IgG1, IgG2a, and IgG2b antibodies on day 35. Data shown are median ± IQR. Each dot represents an individual mouse. GMT in the antibody assay indicates geometric mean titers. Data reflect 2 independent experiments (n = 3/antigen-only group; n = 4/Alum, AddaVax, AddaS03, or L-pampo (L) group; n = 2/CpG-Alum group in single experiment). Asterisks indicate statistically significant differences in comparison to the L-pampo (L) group. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; one way ANOVA with the Tukey’s test. Full article ">Figure 4
RBD-Fc antigen with L-pampo induces cell-mediated responses. (A,B) BALB/c mice (total n = 42; n = 6/antigen-only; n = 8/Alum, AddaVax, AddaS03, or L-pampo (L); n = 4/CpG–Alum) were immunized with RBD-Fc with or without adjuvants i.m. on day 0 and day 21 as described in <a href="#vaccines-09-00957-f003" class="html-fig">Figure 3</a>A. On day 35, splenocytes were stimulated with the PepMixTM SARS-CoV-2(S-RBD) peptide pool, and RBD-specific IFN-γ secreting cells were analyzed as SFCs by ELISPOT assay (A) or total IFN-γ production by ELISA assay (B). Data shown are median ± IQR. Each dot represents an individual mouse. Data reflect 2 independent experiments (n = 3/antigen-only group; n = 4/Alum, AddaVax, AddaS03, or L-pampo (L) group; n = 2/CpG–Alum group in single experiment). Asterisks indicate statistically significant differences in comparison to the L-pampo (L) group. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; one way ANOVA with the Tukey’s test. Full article ">Figure 5
RBD and S1 antigens with L-pampo induce robust humoral and cellular responses in the ferret model. (A) A schematic of the immunization and virus challenge strategy in the ferret model. Ferrets (total n = 16, n = 4/PBS; n = 6/Ag only; n = 6/Ag + L-pampo) were immunized with the SARS-CoV-2 antigens (RBD and S1 with 30 μg per each) with L-pampo i.m. on day 0 and day 14. The antigen-only and PBS groups were as controls. On day 35, ferrets were intranasally challenged with 105.5 50% tissue culture infective doses (TCID50/mL) SARS-CoV-2 (Korea Centers for Disease Control and Prevention; resource no. 43326) under anesthesia. Blood was collected every week for 5 weeks from the first immunization. After virus challenge, the nasal wash was collected on days 2, 4, 6, 8, 10, and 12. (B) Neutralizing antibody production on day 35 prior to challenge of virus. (C) On day 35, ferret PBMCs were stimulated with the RBD or S1 antigen and RBD or S1-specific IFN-γ-secreting cells were analyzed as SFCs by ELISPOT assay. (D) Viral load in nasal wash on days 2, 4, 6, and 12 after virus challenge by using a TCID50 assay. Dotted lines represent lower limits of detection. Data shown are median ± IQR. Each dot represents an individual ferret. Data reflect 2 independent experiments (n = 2/PBS group; n = 3/Ag only or Ag + L-pampo group in single experiment). * p < 0.05; ** p < 0.01; two tailed Mann–Whiteny test (B); one way ANOVA with the Tukey’s test (C,D). Full article ">Figure 6
Signs of clinical symptoms after SARS-CoV-2 virus challenge. Immunized ferrets (total n = 16, n = 4/PBS; n = 6/Ag only; n = 6/Ag + L-pampo) were intranasally challenged with 105.5 TCID50/mL SARS-CoV-2 (Korea Centers for Disease Control and Prevention, resource no. 43326) under anesthesia. The body weight (%) (A) and temperature (°C) (B) of ferrets on days 2, 4, 6, 8, and 10 after SARS-CoV-2 virus challenge. Data shown are mean ± SD. Full article ">

7 pages, 786 KiB

Open AccessBrief Report

Rhabdomyolysis Following Ad26.COV2.S COVID-19 Vaccination

by Georg Gelbenegger, Filippo Cacioppo, Christa Firbas and Bernd Jilma

Vaccines 2021, 9(9), 956; https://doi.org/10.3390/vaccines9090956 - 27 Aug 2021

Cited by 17 | Viewed by 6846

Abstract

We report the case of a 19-year-old male who complained of myalgia, muscle weakness, and darkened urine two days after receiving his Ad26.COV2.S (Johnson & Johnson, New Brunswick, New Jersey, United States) COVID-19 vaccination. Blood examination revealed an increased creatine kinase (CK) level, [...] Read more.

We report the case of a 19-year-old male who complained of myalgia, muscle weakness, and darkened urine two days after receiving his Ad26.COV2.S (Johnson & Johnson, New Brunswick, New Jersey, United States) COVID-19 vaccination. Blood examination revealed an increased creatine kinase (CK) level, and his urinary dipstick tested positive for blood, indicative of acute rhabdomyolysis. Serum creatinine levels were normal. Rhabdomyolysis due to strenuous physical activity was ruled out and further diagnostics excluded an autoimmune cause. Under repeated treatment with intravenous fluid resuscitation (outpatient treatment), his symptoms resolved and peak CK levels of 44,180 U/L returned to almost normal levels within two weeks. Rhabdomyolysis is a rare, potentially fatal vaccine-induced reaction. Further research is needed to better understand the underlying pathomechanism and to investigate whether subcutaneous injection of vaccines may be able to prevent rhabdomyolysis. Full article

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7 pages, 382 KiB

Open AccessArticle

Persistence of Anti-S Titre among Healthcare Workers Vaccinated with BNT162b2 mRNA COVID-19

by Luca Coppeta, Giuseppina Somma, Cristiana Ferrari, Andrea Mazza, Stefano Rizza, Marco Trabucco Aurilio, Stefano Perrone, Andrea Magrini and Antonio Pietroiusti

Vaccines 2021, 9(9), 947; https://doi.org/10.3390/vaccines9090947 - 25 Aug 2021

Cited by 20 | Viewed by 3476

Abstract

The COVID-19 pandemic has led to health, social and economic consequences for public health systems. As a result, the development of safe and effective vaccines, in order to contain the infection quickly became a priority. The first vaccine approved by the Italian Agency [...] Read more.

The COVID-19 pandemic has led to health, social and economic consequences for public health systems. As a result, the development of safe and effective vaccines, in order to contain the infection quickly became a priority. The first vaccine approved by the Italian Agency for Drugs Authorization (AIFA) was the BNT162b2 mRNA vaccine, developed by BioNTech and Pfizer (Comirnaty). Comirnaty contains a molecule called messenger RNA (mRNA), which is a nucleoside-modified RNA that encodes the SARS-CoV-2 spike glycoprotein. Even if data from phase I suggest that vaccine induced antibodies can persist for up to six months following the second shot of BNT vaccine, data regarding the real duration of immunological protection are lacking. In this study, we aimed to evaluate the duration of serological protection by detecting the presence of anti-S-RBD (receptor-binding domain) antibodies for SARS-CoV-2 among a large group of healthcare workers (HCWs) three months after vaccination. 99% of HCWs had a detectable titre of anti-S SARS-CoV-2 antibodies 90 days after the second vaccine shot. Elderly operators showed significantly lower levels of protective antibodies when compared to the younger ones, thus they could become unprotected earlier than other operators. Full article

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11 pages, 242 KiB

Open AccessArticle

Predictors of COVID-19 Vaccine Intention among the Saudi Arabian Population: A Cross-Sectional Survey

by Mohammed Noushad, Mohammad Zakaria Nassani, Pradeep Koppolu, Anas B. Alsalhani, Abdulaziz Samran, Ali Alqerban, Ghadah Salim Abusalim, Ali Barakat, Mashari Bandar Alshalhoub and Samer Rastam

Vaccines 2021, 9(8), 892; https://doi.org/10.3390/vaccines9080892 - 12 Aug 2021

Cited by 17 | Viewed by 3725

Abstract

The long-term solution to managing the current COVID-19 pandemic is through mass immunization of the population. However, uncertainty or unwillingness to receive the vaccine could be a barrier in attaining sufficient vaccine coverage. Therefore, understanding the psychology of the population towards the vaccines [...] Read more.

The long-term solution to managing the current COVID-19 pandemic is through mass immunization of the population. However, uncertainty or unwillingness to receive the vaccine could be a barrier in attaining sufficient vaccine coverage. Therefore, understanding the psychology of the population towards the vaccines against COVID-19 is of paramount importance. Our study was aimed at determining the predictors of COVID-19 vaccine intention in the Saudi Arabian population. A structured questionnaire guided by the ‘Report of the SAGE working group on vaccine hesitancy’ was administered during a span of two months among the general population from all administrative regions of Saudi Arabia, proceeding the launch of the vaccination campaign. In total, 879 out of 1600 subjects responded and completed the survey (response rate 54.9%). About 56 percent of the participants intended to be vaccinated. The predictors of a higher intention to vaccinate included those 50 years of age or older, male subjects, people suffering from systemic disease/s, subjects who were not previously infected with COVID-19, those who follow the updates about COVID-19 vaccines, and adults with a higher level of anxiety about contracting coronavirus (p < 0.05). Results from our study and other similar studies can aid policy makers and stakeholders in planning effective strategies based on the changing behavior of the population. Full article

7 pages, 867 KiB

Open AccessCommunication

Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis after COVID-19 Vaccination

by Saki Okuda, Yasuaki Hirooka and Masafumi Sugiyama

Vaccines 2021, 9(8), 842; https://doi.org/10.3390/vaccines9080842 - 31 Jul 2021

Cited by 22 | Viewed by 5093

Abstract

We report the case of a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after receiving the coronavirus disease 2019 (COVID-19) vaccine BNT162b (Pfizer–BioNTech). A 37-year-old Japanese woman had been taking propylthiouracil for Graves’ disease. She had erythema on her forearm on [...] Read more.

We report the case of a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after receiving the coronavirus disease 2019 (COVID-19) vaccine BNT162b (Pfizer–BioNTech). A 37-year-old Japanese woman had been taking propylthiouracil for Graves’ disease. She had erythema on her forearm on the 12th day after receiving the first dose of the vaccine, fever on the 13th day, and redness and swelling of her left auricle on the 25th day. Her serum myeloperoxidase-ANCA and proteinase 3-ANCA levels, which were negative before the Graves’ disease treatment, were elevated. She had unilateral auricular symptoms but no other typical relapsing polychondritis findings. She was diagnosed with propylthiouracil-induced AAV. She was treated with oral glucocorticoids, and her symptoms improved. Propylthiouracil is considered to be the main cause of the onset of AAV in this case, but it cannot be ruled out that BNT162b may have had some effect on the onset of the disease. Although the development of propylthiouracil-induced AAV in this case may have been incidental and unrelated to the vaccination, this report provides important data for evaluating the safety of the vaccine. Full article

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13 pages, 7025 KiB

Open AccessArticle

A Glimpse into the Diverse Cellular Immunity against SARS-CoV-2

by Cheng-Wei Chang, Yuchen Liu, Cheng Jiao, Hongwei Liu, Jie Gong, Xiaochuan Chen and Lung-Ji Chang

Vaccines 2021, 9(8), 827; https://doi.org/10.3390/vaccines9080827 - 27 Jul 2021

Cited by 1 | Viewed by 3002

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its variants, we hypothesized that vaccines that target multiple T-cell epitopes of SARS-CoV-2 may provide a “universal protection” against the wild-type virus as well as its variants, even the heavily mutated ones. To test this, we assessed SARS-CoV-2-specific T-cell precursors in healthy individuals using overlapping peptide pools of SARS-CoV-2 structural and functional proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N), and protease (P) proteins as target antigens. Diverse T-cell precursor frequencies specific to these viral antigens were detected in healthy individuals, including high, medium, low, and no responders. This was further confirmed by efficient induction of anti-SARS-CoV-2 T-cell immune responses using ex vivo dendritic cell (DC)/T cell coculture. The results demonstrated T-cell responses consistent with the precursor frequencies of each of the individuals tested. Importantly, the combination of all five viral peptide pools induced the strongest cellular immune response, and further, after a DC-peptides re-stimulation, even the no responders developed an increased anti-viral T-cell response. These analyses recapitulate the presence of a broad anti-SARS-CoV-2 cellular immunity even in an immune naïve population, which could be enhanced by antigen presenting cells presenting the overlapping antigenic peptides. Given the critical role of cellular immunity in COVID-19 protection, these results have important implications for vaccine design and immunotherapy in fighting SARS-CoV-2 and its variants. Full article

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Synthetic peptides of SARS-CoV-2 S, E, M, N, and P proteins and in vitro generation of antigen-specific T cells. (A) Schematic illustration of SARS-CoV-2 particle. (B) Representative S, E, M, N, and P protein domains. (C) Diagram of in vitro antigen-specific T cell generation. DCs and T lymphocytes were prepared from PBMCs and synthetic viral peptide-pulsed DCs were used as antigen presenting cells (APCs) to activate T cells. Full article ">Figure 2
SARS-CoV-2 specific T-cell precursor frequencies in healthy subjects. (A) IFN-γ ELISPOT assay. PBMCs of 30 healthy subjects were activated in vitro with individual or pooled S, E, M, N, and P peptide mixes, and IFN-γ reactive cells were detected. PHA activated T cells were used as positive controls. The HIV-1 Pol peptide pool was included as background control as all donors were HIV-1-negative. The group (PBMC) without antigen stimulation was also included as background control. Representative ELISPOT wells are shown on top, and the machine-documented spot numbers listed below were the mean values of duplicates for all 30 donors. (B) The number of spot-forming cells after background subtraction per indicated target antigens (below the background levels were shown as 0). Each symbol represents a peptide pool, and different colors represent different subjects. The bar represents the median response value of all subjects to each antigen peptide pool after deducting the background value. (C) Pie graph illustration of the diverse individual cellular immune response to the different viral antigens based on fold of increase of spot forming cells. The color classification of individual response illustrates different ranges of IFN-γ specific spots: high responder, >3 fold of increase in spots; medium responder, 2–3 fold of increase; low responder, 1.5–2 fold of increase; and no responder, <1.5 fold of increase. Full article ">Figure 3
Primary activated T cells for 12 days against SARS-CoV-2 antigens. (A) IFN-γ ELISPOT assay of T cells from selected responders. T cells were cultured for 12 days from the different subjects including no, low, medium, and high responders. PHA treatment served as positive control, and HIV-1 peptides and CTL without antigen served as background controls. (B) Bar graph analysis of the IFN-γ specific T-cell expansion fold of increase based on spot-forming cells against the different viral antigens for the five subjects. The error bars depict the variation range of the duplicates. Full article ">Figure 4
Secondary DC/T-cell activation at 30 days against SARS-CoV-2 antigens. (A) IFN-γ ELISPOT assay of two no responders after secondary antigen activation. The T cells after primary and secondary DC activation were cultured for 30 days from two no response donors. PHA served as a positive control, and HIV-1 peptide pools and CTL without antigen stimulation served as background controls. (B) The comparison of primary day 12 versus secondary day 30 IFN-γ spot expansion folds of T cells against indicated target antigens. Full article ">Figure 5
Effector function analyses of T cells against SARS-CoV-2 SEMNP antigens. After DC–T-cell coculture, the viral antigen-specific CTLs were analyzed for cytokine release and CD107a degranulation by intracellular staining and flow cytometry. The TNF-α, IFN-γ, IL-2, and CD107a production in T cells were illustrated in the FACS graphs after stimulations with SARS-CoV-2 antigenic peptides. PMA and ionomycin (PMA + ION) activation served as positive control, and HIV-1 peptide pools and CTL without antigen served as background controls. Flow cytometry analyses of TNF-α, IL-2, IFN-γ, and CD107a-positive cells in CD4-gated or CD8-gated populations of the representative subjects are illustrated. (A) The gated CD3 and CD8 T-cell populations and the control isotype antibody staining of the intracellular effectors. (B) Flow cytometry analysis of intracellular IFN-γ and CD107a in CD3, CD4, and CD8 gated populations. (C) Flow cytometry analysis of intracellular TNF-α and IL-2 in CD3, CD4, and CD8 gated populations. Full article ">Figure 5 Cont.
Effector function analyses of T cells against SARS-CoV-2 SEMNP antigens. After DC–T-cell coculture, the viral antigen-specific CTLs were analyzed for cytokine release and CD107a degranulation by intracellular staining and flow cytometry. The TNF-α, IFN-γ, IL-2, and CD107a production in T cells were illustrated in the FACS graphs after stimulations with SARS-CoV-2 antigenic peptides. PMA and ionomycin (PMA + ION) activation served as positive control, and HIV-1 peptide pools and CTL without antigen served as background controls. Flow cytometry analyses of TNF-α, IL-2, IFN-γ, and CD107a-positive cells in CD4-gated or CD8-gated populations of the representative subjects are illustrated. (A) The gated CD3 and CD8 T-cell populations and the control isotype antibody staining of the intracellular effectors. (B) Flow cytometry analysis of intracellular IFN-γ and CD107a in CD3, CD4, and CD8 gated populations. (C) Flow cytometry analysis of intracellular TNF-α and IL-2 in CD3, CD4, and CD8 gated populations. Full article ">

20 pages, 1256 KiB

Open AccessArticle

Acceptance of COVID-19 Vaccination in Cancer Patients in Hong Kong: Approaches to Improve the Vaccination Rate

by Wing-Lok Chan, Yuen-Hung Tricia Ho, Carlos King-Ho Wong, Horace Cheuk-Wai Choi, Ka-On Lam, Kwok-Keung Yuen, Dora Kwong and Ivan Hung

Vaccines 2021, 9(7), 792; https://doi.org/10.3390/vaccines9070792 - 16 Jul 2021

Cited by 26 | Viewed by 4744

Abstract

Emerging efficacy and safety data have led to the authorization of COVID-19 vaccines worldwide, but most trials excluded patients with active malignancies. This study evaluates the intended acceptance of COVID-19 vaccination in cancer patients in Hong Kong. Methods: 660 adult cancer patients received [...] Read more.

Emerging efficacy and safety data have led to the authorization of COVID-19 vaccines worldwide, but most trials excluded patients with active malignancies. This study evaluates the intended acceptance of COVID-19 vaccination in cancer patients in Hong Kong. Methods: 660 adult cancer patients received a survey, in paper or electronic format, between 31 January 2021 and 15 February 2021. The survey included patient’s clinical characteristics, perceptions of COVID-19 and vaccination, vaccine knowledge, cancer health literacy, and Hospital Anxiety and Depression scale (HADS). The primary outcome was the intended acceptance of COVID-19 vaccine in cancer patients. Multivariable analysis was performed to identify factors associated with intended acceptance. Results: The intended acceptance of COVID-19 vaccination was 17.9%. A total of 487 (73.8%) believed that vaccination could prevent them from infection. Over 70% worried about vaccine negative effects on cancer and its side effects. Factors associated with intended acceptance included higher level of “belief in vaccine on preventing them from getting COVID-19”, less worry about long-term side effects of vaccine, lower level of cancer health literacy, and normal HADS (Depression scale). Conclusions: To improve vaccine acceptance rate, public education campaigns specific to cancer patients to gain their trust in efficacy and relieve their worries are needed. Full article

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10 pages, 713 KiB

Open AccessArticle

Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine

by Piotr Rzymski, Monika Pazgan-Simon, Krzysztof Simon, Tadeusz Łapiński, Dorota Zarębska-Michaluk, Barbara Szczepańska, Michał Chojnicki, Iwona Mozer-Lisewska and Robert Flisiak

Vaccines 2021, 9(7), 781; https://doi.org/10.3390/vaccines9070781 - 13 Jul 2021

Cited by 28 | Viewed by 9329

Abstract

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may [...] Read more.

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)—three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure. Full article

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18 pages, 690 KiB

Open AccessReview

Multiple Sclerosis, Disease-Modifying Therapies and COVID-19: A Systematic Review on Immune Response and Vaccination Recommendations

by Verónica Cabreira, Pedro Abreu, Ricardo Soares-dos-Reis, Joana Guimarães and Maria José Sá

Vaccines 2021, 9(7), 773; https://doi.org/10.3390/vaccines9070773 - 11 Jul 2021

Cited by 32 | Viewed by 7692

Abstract

Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to [...] Read more.

Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3–6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4–6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols. Full article

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9 pages, 773 KiB

Open AccessReview

A Quantitative ELISA Protocol for Detection of Specific Human IgG against the SARS-CoV-2 Spike Protein

by Rémi Vernet, Emily Charrier, Julien Grogg and Nicolas Mach

Vaccines 2021, 9(7), 770; https://doi.org/10.3390/vaccines9070770 - 9 Jul 2021

Cited by 11 | Viewed by 5295

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with at least 3.8 million deaths to date. For that reason, finding an efficient vaccine for this virus quickly became a global priority. The majority of vaccines now marketed are based [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with at least 3.8 million deaths to date. For that reason, finding an efficient vaccine for this virus quickly became a global priority. The majority of vaccines now marketed are based on the SARS-CoV-2 spike protein that has been described as the keystone for optimal immunization. In order to monitor SARS-CoV-2 spike-specific humoral responses generated by immunization or infection, we have developed a robust and reproducible enzyme-linked immunosorbent assay (ELISA) protocol. This protocol describes a method for quantitative detection of IgG antibodies against the SARS-CoV-2 spike protein using antigen-coated microtiter plates. Results showed that antibodies could be quantified between the range of 1.953 ng/mL to 500 ng/mL with limited inter- and intra-assay variability. Full article

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8 pages, 361 KiB

Open AccessCommunication

Humoral Response to SARS-Cov-2 Vaccination in Liver Transplant Recipients–A Single-Center Experience

by Jassin Rashidi-Alavijeh, Alexandra Frey, Moritz Passenberg, Johannes Korth, Jaqueline Zmudzinski, Olympia E. Anastasiou, Fuat H. Saner, Michael Jahn, Christian M. Lange and Katharina Willuweit

Vaccines 2021, 9(7), 738; https://doi.org/10.3390/vaccines9070738 - 4 Jul 2021

Cited by 54 | Viewed by 3961

Abstract

Vaccination against SARS-CoV-2 infection is currently approved and shows favorable outcomes, but little known about antibody responses in solid organ transplant recipients, since these patients are known to have an impaired immune response upon vaccination and have not been included in admission studies. [...] Read more.

Vaccination against SARS-CoV-2 infection is currently approved and shows favorable outcomes, but little known about antibody responses in solid organ transplant recipients, since these patients are known to have an impaired immune response upon vaccination and have not been included in admission studies. We therefore analyzed immunogenicity in 43 liver transplant (LT) recipients in a median of 15 days (IQR, 12–24) after receiving two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol, and compared these results to a control group consisting of 20 healthcare workers (HCWs). Thirty-four of the 43 (79%) LT recipients developed antibodies, compared to 20 out of 20 (100%) in the control group (p = 0.047). The median SARS-CoV-2 IgG titer was significantly lower in the LT recipients compared to the control group (216 vs. >2080 BAU/mL, p = 0.0001). Age and sex distribution was similar in the LT patients that developed antibodies after vaccination compared to those who did not. Interestingly, the patients who received mycophenolate mofetil exhibited a reduced vaccination response compared to the other LT patients (5 of 11 (45.5%) vs. 29 of 32 (90.6%), p = 0.004). In conclusion, our data reveal lower immunogenicity of SARS-CoV-2 vaccine BNT162b2 in LT patients compared to the control group, but still show superior results compared to other solid organ transplant recipients reported so far. Full article

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7 pages, 519 KiB

Open AccessCommunication

Understanding Soaring Coronavirus Cases and the Effect of Contagion Policies in the UK

by Miguel A. Durán-Olivencia and Serafim Kalliadasis

Vaccines 2021, 9(7), 735; https://doi.org/10.3390/vaccines9070735 - 3 Jul 2021

Cited by 1 | Viewed by 2612

Abstract

The number of new daily SARS-CoV-2 infections experienced an abrupt increase during the last quarter of 2020 in almost every European country. The phenomenological explanation offered was a new mutation of the virus, first identified in the UK. We use publicly available data [...] Read more.

The number of new daily SARS-CoV-2 infections experienced an abrupt increase during the last quarter of 2020 in almost every European country. The phenomenological explanation offered was a new mutation of the virus, first identified in the UK. We use publicly available data in combination with a time-delayed controlled SIR model, which captures the effects of preventive measures on the spreading of the virus. We are able to reproduce the waves of infection occurred in the UK with a unique transmission rate, suggesting that the new SARS-CoV-2 variant is as transmissible as previous strains. Our findings indicate that the sudden surge in cases was, in fact, related to the relaxation of preventive measures and social awareness. We also simulate the combined effects of restrictions and vaccination campaigns in 2021, demonstrating that lockdown policies are not fully effective to flatten the curve. For effective mitigation, it is critical that the public keeps on high alert until vaccination reaches a critical threshold. Full article

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10 pages, 1051 KiB

Open AccessCommunication

Fusion Protein of Rotavirus VP6 and SARS-CoV-2 Receptor Binding Domain Induces T Cell Responses

by Kirsi Tamminen, Suvi Heinimäki, Stina Gröhn and Vesna Blazevic

Vaccines 2021, 9(7), 733; https://doi.org/10.3390/vaccines9070733 - 2 Jul 2021

Cited by 6 | Viewed by 3288

Abstract

Vaccines based on mRNA and viral vectors are currently used in the frontline to combat the ongoing pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, there is still an urgent need for alternative vaccine technologies inducing/boosting long-lasting and cross-reactive [...] Read more.

Vaccines based on mRNA and viral vectors are currently used in the frontline to combat the ongoing pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, there is still an urgent need for alternative vaccine technologies inducing/boosting long-lasting and cross-reactive immunity in different populations. As a possible vaccine candidate, we employed the rotavirus VP6-protein platform to construct a fusion protein (FP) displaying receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) at the N-terminus of VP6. The recombinant baculovirus-insect cell produced VP6-RBD FP was proven antigenic in vitro and bound to the human angiotensin-converting enzyme 2 (hACE2) receptor. The FP was used to immunize BALB/c mice, and humoral- and T cell-mediated immune responses were investigated. SARS-CoV-2 RBD-specific T cells were induced at a high quantity; however, no RBD or S-specific antibodies were detected. The results suggest that conformational B cell epitopes might be buried inside the VP6, while RBD-specific T cell epitopes are available for T cell recognition after the processing and presentation of FP by the antigen-presenting cells. Further immunogenicity studies are needed to confirm these findings and to assess whether, under different experimental conditions, the VP6 platform may present SARS-CoV-2 antigens to B cells as well. Full article

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Characterization of VP6-RBD fusion protein. Rotavirus VP6 protein was used as a backbone to generate fusion protein (FP) carrying SARS-CoV-2 Spike (S) protein derived receptor-binding domain (RBD) as described in the Materials and Methods. The FP was crude purified from Sf9 insect cell pellets after 6-day culture with recombinant baculovirus and separated (5 μg/lane of total protein) under reducing conditions in SDS-PAGE following staining with Coomassie blue (a) or immunoblotting using primary antibodies against VP6 (b) or SARS-CoV-2 S protein (c). VP6-RBD FP (~70 kDa) before (A) and after (B) final clarification step is indicated by an arrow (a–c). Wild-type VP6 (~42 kDa) and commercial RBD protein (~23 kDa, migrating as a higher molecular weight due to glycosylation) were used as positive controls in SDS-PAGE and/or Western blot. Molecular weight marker (M) is shown with the respective molecular sizes (kDa). Binding of VP6-RBD, SARS-CoV-2 S (CoV-2 S, a positive control), and SARS-CoV-2 nucleoprotein (CoV-2 NP, a negative control) to immobilized human angiotensin-converting enzyme 2 (hACE2) by an ELISA-based binding assay (d). Optical density (OD) values at 490 nm of VP6-RBD (0–2.4 µg/well), CoV-2 S, and NP (both 0–0.04 µg/well) binding to 0.05 µg/well hACE2 are shown. Full article ">Figure 2
SARS-CoV-2 and VP6-specific antibody and T cell responses. Serum IgG antibody responses in mice following immunization with VP6-SARS-CoV-2 receptor-binding domain (VP6-RBD) fusion protein (FP), SARS-CoV-2 Spike (CoV-2 S, a positive control), or carrier only (PBS, a negative control) were analyzed by antigen-specific ELISAs and/or Western blot. SARS-CoV-2 S, RBD, and nucleoprotein (NP)-specific IgG antibodies are shown, represented by mean optical density (OD) values with standard error of the mean (SEM) of sera diluted 1:100 (a) and serum titration curves of CoV-2 S immunized mice (b). VP6-RBD FP immune sera were further used as a pool of individual sera (1:100 dilution) to detect SARS-CoV-2 RBD, S, and VP6 (each 1μg/lane) proteins under denaturing conditions in a Western blot (c). Molecular weight marker (M) is shown with the respective molecular sizes (kDa). VP6-specific IgG responses of VP6-RBD FP immunized and control mice are illustrated by mean OD values with SEM (d) and geometric mean titer (GMT) with 95% confidence intervals (e). If the starting dilution resulted in an OD value below the set cutoff, the sample was given an arbitrary value half of the starting dilution (ctrl, (e)). T cell responses of immunized and control mice splenocytes were analyzed by ELISPOT IFN-γ against SARS-CoV-2 S1 and NP (a negative control) peptide pool stimulation (f). Cell culture medium (CM) alone was used to determine background cytokine release. Mean IFN-γ spot-forming cells (SFC)/106 live splenocytes of duplicate wells with SEM are shown. Dashed horizontal lines in the panels represent the cutoff value for ELISA ((a,b,d,e), mean OD490 + 3 × SD and at least 0.1 OD of negative control mice) and ELISPOT ((f), mean SFC/106 cells + 3 × SD of CM wells). Statistical significance was defined as p < 0.05 and hypothesis testing was two tailed. ns: not significant p-value. Full article ">

8 pages, 940 KiB

Open AccessCommunication

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines

by Madhusudhanan Narasimhan, Lenin Mahimainathan, Andrew E Clark, Amena Usmani, Jing Cao, Ellen Araj, Fernando Torres, Ravi Sarode, Vaidehi Kaza, Chantale Lacelle and Alagarraju Muthukumar

Vaccines 2021, 9(7), 708; https://doi.org/10.3390/vaccines9070708 - 30 Jun 2021

Cited by 52 | Viewed by 4063

Abstract

Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we [...] Read more.

Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines’ 2D regimen on anti-spike responses in immunocompromised LT recipients. Methods: We utilized serum samples from LT recipients vaccinated for SARS-CoV-2 with 2D of either the Pfizer-BioNTech or Moderna vaccines and 2D-vaccinated naïve (non-transplanted and non-exposed to COVID-19) group. Antibody responses were assessed using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgG_NC), the SARS-CoV-2 anti-spike protein IgM assay (IgM_SP), and the SARS-CoV-2 anti-spike protein IgG II assay (IgG_SP). CD4+ T-cell activity was assessed as a marker of immune competence using the ImmuKnow^® assay. Results: About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated a positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited a significantly lesser median IgG_SP response (1.7 AU/mL, 95% CI: 0.6–7.5 AU/mL) compared to non-transplanted, uninfected naïve subjects (14,209 AU/mL, 95% CI: 11,261–18,836 AU/mL; p < 0.0001). In LT patients, the Moderna-evoked seropositivity trend was higher than Pfizer. Conclusion: 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with a higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation. Full article

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9 pages, 1296 KiB

Open AccessCommunication

Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results

by Wojciech Zdanowski and Tomasz Waśniewski

Vaccines 2021, 9(6), 675; https://doi.org/10.3390/vaccines9060675 - 19 Jun 2021

Cited by 44 | Viewed by 9586

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has given rise to the need to develop a vaccine as quickly as possible. As pregnant women are at increased risk of contracting severe COVID-19, with higher mortality, it is essential to assess the safety of [...] Read more.

Background: The coronavirus disease 2019 (COVID-19) pandemic has given rise to the need to develop a vaccine as quickly as possible. As pregnant women are at increased risk of contracting severe COVID-19, with higher mortality, it is essential to assess the safety of the vaccines administered during pregnancy. Methods: The aim of this study was to determine the titer of specific maternal and cord antibodies against severe acute respiratory syndrome coronavirus 2 S protein after antenatal vaccination. The secondary objective was to evaluate the ratio of the umbilical cord to the maternal antibody titers. Patients included in the study were enrolled after undergoing voluntary vaccination against COVID-19 during pregnancy at different weeks of gestation. All patients analyzed in our initial study were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Results: The results of the current study document high anti-S total IgG antibody titers in cord serum at birth in all mother–infant pairs analyzed. The mean umbilical cord blood sample IgG antibody titer anti-S protein was 1026.51 U/mL (±SD 769.25). The mean cord-to-maternal anti–S IgG antibody ratio was 1.28 (±SD 0.798). A significant positive correlation was observed between the week of gestation at which the first dose was administered and the week of gestation at which the second dose was administered, and the respective cord-to-maternal ratio (r = 0.48; p = 0.0029) for the first dose and (r = 0.39; p = 0.0102) for the second dose. Conclusions: To date, despite the prevalence of COVID-19 vaccination, there is a lack of conclusive evidence supporting the safety and efficacy of vaccination of pregnant women. Therefore, the results we present are complementary. Our study suggests that maternal immunization may provide neonatal protection through the transplacental transfer of antibodies. Of particular importance is the demonstration that antibody transfer is correlated with the time from vaccination to delivery, which may allow future determination of the optimal timing of COVID-19 vaccination in pregnant women. Full article

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Mean time (weeks) from the first and the second dose of vaccine to delivery. Full article ">Figure 2
Mean anti-S antibody titers in maternal and umbilical cord blood. Full article ">Figure 3
Correlation between the number of weeks from the first vaccine dose to delivery and the anti-S antibody titer in cord blood serum. Full article ">Figure 4
Correlation between the period (weeks) from the first vaccine dose to delivery and cord-to-maternal anti-S titer ratio. Full article ">Figure 5
Correlation between the period (weeks) from the second vaccine dose to delivery and cord-to-maternal anti-S titer ratio. Full article ">Figure 6
Correlation between the week of gestation when the first vaccine dose was administered and cord-to-maternal anti-S titer ratio. Full article ">Figure 7
Correlation between the week of gestation when the second vaccine dose was administered and cord-to-maternal anti-S titer ratio. Full article ">

16 pages, 2567 KiB

Open AccessArticle

Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy

by Mauro Turrini, Angelo Gardellini, Livia Beretta, Lucia Buzzi, Stefano Ferrario, Sabrina Vasile, Raffaella Clerici, Andrea Colzani, Luigi Liparulo, Giovanni Scognamiglio, Gianni Imperiali, Giovanni Corrado, Antonello Strada, Marco Galletti, Nunzio Castiglione and Claudio Zanon

Vaccines 2021, 9(6), 640; https://doi.org/10.3390/vaccines9060640 - 11 Jun 2021

Cited by 3 | Viewed by 4033

Abstract

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that [...] Read more.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (−0.37), antiviral lopinavir/ritonavir (−1.22), or steroid (−0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease. Full article

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5 pages, 206 KiB

Open AccessCommunication

COVID-19 Vaccination in Patients with Classic Kaposi’s Sarcoma

by Alice Indini, Athanasia Tourlaki, Francesco Grossi, Donatella Gambini and Lucia Brambilla

Vaccines 2021, 9(6), 632; https://doi.org/10.3390/vaccines9060632 - 10 Jun 2021

Cited by 3 | Viewed by 3510

Abstract

The novel coronavirus disease 2019 (COVID-19) has represented an overwhelming challenge for worldwide health systems. Patients with cancer are considered at higher risk for severe COVID-19 and increased mortality in case of infection. Although data on the novel severe acute respiratory syndrome coronavirus [...] Read more.

The novel coronavirus disease 2019 (COVID-19) has represented an overwhelming challenge for worldwide health systems. Patients with cancer are considered at higher risk for severe COVID-19 and increased mortality in case of infection. Although data on the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with cancer are limited, there is enough evidence supporting anti-infective vaccination in general in patients with active cancer, or with history of previous malignancy. Subjects with classic Kaposi’s sarcoma (KS) represent a small subset of cancer patients, which should be considered at heightened risk for infections due to several factors including age, and impaired immune function status. Several cases of human herpesviruses reactivation among critically ill COVID-19 patients have been described. Moreover, in case of severe infection and treatment with immunomodulating agents, patients with CKS are exposed at significant risk of viral reactivation and disease progression. Considering the baseline clinical risk factors of patients with CKS, and the complex interplay of the two viral agents, SARS-CoV-2 vaccination should be strongly recommended among patients with KS. KS represents an interesting field to study the interactions among chronic viral infections, SARS-CoV-2 and the host’s immune system. Prospective observational studies are needed to provide more insights on vaccine activity and safety among patients with cancer, optimal vaccine schedules, potential interactions with antineoplastic therapies, and other comorbidities including chronic viral infections. Full article

9 pages, 1671 KiB

Open AccessBrief Report

A Unique SARS-CoV-2 Spike Protein P681H Variant Detected in Israel

by Neta S. Zuckerman, Shay Fleishon, Efrat Bucris, Dana Bar-Ilan, Michal Linial, Itay Bar-Or, Victoria Indenbaum, Merav Weil, Yaniv Lustig, Ella Mendelson, Michal Mandelboim, Orna Mor, Neta Zuckerman and on behalf of the Israel National Consortium for SARS-CoV-2 Sequencing

Vaccines 2021, 9(6), 616; https://doi.org/10.3390/vaccines9060616 - 8 Jun 2021

Cited by 22 | Viewed by 4708

Abstract

The routine detection, surveillance, and reporting of novel SARS-CoV-2 variants is crucial, as these threaten to hinder global vaccination efforts. Herein we report a novel local variant with a non-synonymous mutation in the spike (S) protein P681H. This local Israeli variant was not [...] Read more.

The routine detection, surveillance, and reporting of novel SARS-CoV-2 variants is crucial, as these threaten to hinder global vaccination efforts. Herein we report a novel local variant with a non-synonymous mutation in the spike (S) protein P681H. This local Israeli variant was not associated with a higher infection rate or higher prevalence. Furthermore, the local variant was successfully neutralized by sera from fully vaccinated individuals at a comparable level to the B.1.1.7 variant and an Israel wild-type strain. While it is not a variant of concern, routine monitoring by sequencing is still required. Full article

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Characterization of the B.1.1.50 + P681H variant. Phylogenetic trees highlighting the genotype at site 681 in the S protein, with the wild-type proline (P) in green and the mutations histidine (H) and arginine (R) in yellow and blue, respectively. (A) SARS-CoV-2 genomes sequenced in Israel from March 2020 to January 2021 (n = 2482). The main clusters harboring the P681H mutation (in yellow) are the B.1.1.7 (20I/501Y.V1) and the B.1.1.50 + P681H variant. (B) SARS-CoV-2 genomes from of the B.1.1.50 lineage only (n = 489). The B.1.1.50 + P681H cluster is composed of local (Israel) viruses only, with the exception of 2 sequences from isolates identified in the Palestinian authorities, and includes a sub-cluster with an additional S protein non-synonymous mutation, A27S. Additional mutations are listed by each branch. Phylogenetic trees were created with Nextstrain Augur pipeline and visualized with Auspice [<a href="#B3-vaccines-09-00616" class="html-bibr">3</a>]. Non-Israeli B.1.1.50 lineage sequences were downloaded from GISAID and identified with Pangolin classification [<a href="#B4-vaccines-09-00616" class="html-bibr">4</a>]. Full article ">Figure 2
Identification of the P681H mutation in sewers across Israel. Frequency of P681H mutation in SARS-CoV-2 genomes sequenced from nine sewage samples of wastewater treatment plants across Israel each month in August 2020–January 2021. The frequency of the P681H mutation in each region was estimated by measuring the fraction of the mutation from the total number of nucleotides mapped at this position (i.e., depth of sequencing). Full article ">Figure 3
Neutralization of the B.1.1.50 + P681H variant. Neutralization assays were carried out with VERO-E6 cells infected with the B.1.1.50 + P681H variant, B.1.1.7 variant and an Israel WT strain from Israel, using sera from fully vaccinated individuals. On day 6, plates were colorized overnight with Gentian violet +4% formaldehyde solution for virus neutralization. Titers were calculated by qualitative measurements of the cytopathic effect for each patient. Bars represent the geometric mean titer (GMT) and 95% confidence intervals. Full article ">

12 pages, 3491 KiB

Open AccessArticle

Could a New COVID-19 Mutant Strain Undermine Vaccination Efforts? A Mathematical Modelling Approach for Estimating the Spread of B.1.1.7 Using Ontario, Canada, as a Case Study

by Mattew Betti, Nicola Bragazzi, Jane Heffernan, Jude Kong and Angie Raad

Vaccines 2021, 9(6), 592; https://doi.org/10.3390/vaccines9060592 - 3 Jun 2021

Cited by 11 | Viewed by 5814

Abstract

Infections represent highly dynamic processes, characterized by evolutionary changes and events that involve both the pathogen and the host. Among infectious agents, viruses, such as Severe Acute Respiratory Syndrome-related Coronavirus type 2 (SARS-CoV-2), the infectious agent responsible for the currently ongoing Coronavirus disease [...] Read more.

Infections represent highly dynamic processes, characterized by evolutionary changes and events that involve both the pathogen and the host. Among infectious agents, viruses, such as Severe Acute Respiratory Syndrome-related Coronavirus type 2 (SARS-CoV-2), the infectious agent responsible for the currently ongoing Coronavirus disease 2019 (COVID-2019) pandemic, have a particularly high mutation rate. Taking into account the mutational landscape of an infectious agent, it is important to shed light on its evolution capability over time. As new, more infectious strains of COVID-19 emerge around the world, it is imperative to estimate when these new strains may overtake the wild-type strain in different populations. Therefore, we developed a general-purpose framework to estimate the time at which a mutant variant is able to take over a wild-type strain during an emerging infectious disease outbreak. In this study, we used COVID-19 as a case-study; however, the model is adaptable to any emerging pathogen. We devised a two-strain mathematical framework to model a wild- and a mutant-type viral population and fit cumulative case data to parameterize the model, using Ontario as a case study. We found that, in the context of under-reporting and the current case levels, a variant strain was unlikely to dominate until March/April 2021. The current non-pharmaceutical interventions in Ontario need to be kept in place longer even with vaccination in order to prevent another outbreak. The spread of a variant strain in Ontario will likely be observed by a widened peak of the daily reported cases. If vaccine efficacy is maintained across strains, then it is still possible to achieve high levels of immunity in the population by the end of 2021. Our findings have important practical implications in terms of public health as policy- and decision-makers are equipped with a mathematical tool that can enable the estimation of the take-over of a mutant strain of an emerging infectious disease. Full article

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36 pages, 27344 KiB

Open AccessArticle

An Immunoinformatics Approach for SARS-CoV-2 in Latam Populations and Multi-Epitope Vaccine Candidate Directed towards the World’s Population

by Andrés Felipe Cuspoca, Laura Lorena Díaz, Alvaro Fernando Acosta, Marcela Katherine Peñaloza, Yardany Rafael Méndez, Diana Carolina Clavijo and Juvenal Yosa Reyes

Vaccines 2021, 9(6), 581; https://doi.org/10.3390/vaccines9060581 - 1 Jun 2021

Cited by 10 | Viewed by 6144

Abstract

The coronavirus pandemic is a major public health crisis affecting global health systems with dire socioeconomic consequences, especially in vulnerable regions such as Latin America (LATAM). There is an urgent need for a vaccine to help control contagion, reduce mortality and alleviate social [...] Read more.

The coronavirus pandemic is a major public health crisis affecting global health systems with dire socioeconomic consequences, especially in vulnerable regions such as Latin America (LATAM). There is an urgent need for a vaccine to help control contagion, reduce mortality and alleviate social costs. In this study, we propose a rational multi-epitope candidate vaccine against SARS-CoV-2. Using bioinformatics, we constructed a library of potential vaccine peptides, based on the affinity of the most common major human histocompatibility complex (HLA) I and II molecules in the LATAM population to predict immunological complexes among antigenic, non-toxic and non-allergenic peptides extracted from the conserved regions of 92 proteomes. Although HLA-C, had the greatest antigenic peptide capacity from SARS-CoV-2, HLA-B and HLA-A, could be more relevant based on COVID-19 risk of infection in LATAM countries. We also used three-dimensional structures of SARS-CoV-2 proteins to identify potential regions for antibody production. The best HLA-I and II predictions (with increased coverage in common alleles and regions evoking B lymphocyte responses) were grouped into an optimized final multi-epitope construct containing the adjuvants Beta defensin-3, TpD, and PADRE, which are recognized for invoking a safe and specific immune response. Finally, we used Molecular Dynamics to identify the multi-epitope construct which may be a stable target for TLR-4/MD-2. This would prove to be safe and provide the physicochemical requirements for conducting experimental tests around the world. Full article

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Vaccine development pipeline: the design stages of the multi-epitope vaccine proposal are shown. Each stage is important for meeting the objective of identifying peptides capable of generating an immune response, taking into account the most frequent alleles in Latin America. The important servers and cutoff values used in the process are specified. Full article ">Figure 2
Antigenic presentation from the proposed vaccine: The assembly of peptides with vaccine potential are recognised by cell membrane receptors capable of recognising patterns associated with pathogens, such as TLR2 and 4 from dendritic cells. After recognition, the construct is phagocytized by the cell together with TLR, allowing its interaction with MyD88 and the maturation of the phagosome. From the phagosome, the peptide can take two routes: the first route is towards the proteasome, where the peptide is degraded, internalised in the ER and assembled with HLA-I molecules; the second route involves the internalization of the peptide in the late endosome, where it is assembled with HLA-II molecules and subsequently presented on the cell membrane of the LT [<a href="#B103-vaccines-09-00581" class="html-bibr">103</a>,<a href="#B104-vaccines-09-00581" class="html-bibr">104</a>,<a href="#B105-vaccines-09-00581" class="html-bibr">105</a>]. Full article ">Figure 3
Estimation of flexible molecular protein-peptide coupling: In the complexes (upper panels) are two non-redundant HLA-I molecules most frequently found in the Latin American population coupled with a peptide with vaccine potential from SP, namely FAMQMAYRF. (a), Cluster 1, density of 239, <math display="inline"><semantics> <mo>Δ</mo> </semantics></math>G of −5.2. (b), Cluster 1, density of 355, <math display="inline"><semantics> <mo>Δ</mo> </semantics></math>G of −4.9. In the complexes (lower panels) are two non-redundant HLA-II molecules most frequently found in the Latin American population coupled with a peptide with vaccine potential from MG, namely SFRLFARTRSMWSFN. (c), Cluster 1, density of 138, <math display="inline"><semantics> <mo>Δ</mo> </semantics></math>G of −4.6. (d), Cluster 2, density of 168, <math display="inline"><semantics> <mo>Δ</mo> </semantics></math>G of −4.4. Full article ">Figure 4
Construction of the Proposed Multi-Epitope Vaccine. Structure of the multi-epitope construct: three-dimensional diagrammatic structure of the multi-epitope construct showing (a), the separators, origin of the peptides and adjuvants used; (b), the location of the adjuvants PADRE, TpD and M cell ligand; and (c), the location of the epitope’s cytotoxic T lymphocytes (CTLs), T helper lymphocytes (HTLs) and B lymphocytes (BLs). (d), Ribbon diagram of the multiepitope construct. Full article ">Figure 5
Analysis of trajectory. (a), Root mean square deviation (RMSD) C<math display="inline"><semantics> <mi>α</mi> </semantics></math> atoms. (b), Root mean square fluctuation for C<math display="inline"><semantics> <mi>α</mi> </semantics></math> atoms (RMSF), TLR-4 receptor initialize at amino acid 1 and goes to amino acid number 1482, and the vaccine from amino acid number 1483 to 1992. (c), Rg plot; vaccine construct is stable in its compact form during the simulation time. (d), Changes in the number of hydrogen bonds between the TLR-4 receptor and multi-epitope vaccine molecule during MD simulation. Full article ">Figure 6
Immune simulation using the multi-epitope construct. (a), BLs, (b), CD4+ TLs and (d), CD8+ TLs were simulated, presenting a cumulative effect towards the third injection on the 56th day of simulation. This suggests the early presence of TLs memory and a change towards the immunoglobulin isotype, immunoglobulin G (IgG), being more predominant. While the antigenic stimulus lasts, there is a polarization towards a certain type of response (c), HTL-1, which is consistent with (e), the active antigenic presentation of professional antigen-presenting cells. This could be partly stimulated by other non-presenters, as well as the production of interleukins, such as (f), IFN <math display="inline"><semantics> <mi>γ</mi> </semantics></math>, TGF-<math display="inline"><semantics> <mi>β</mi> </semantics></math> and IL-2. An infection challenge, composed of a virus responding to the sequence of SARS-CoV-2 proteins covered by the multi-epitope construct, was simulated on day 366. (g), An indifference in immunoglobulin M (IgM) production and increased IgG response suggests favourable conditions for viral antibody clearance in the BLs. (h), The duplication and antigenic presentation of BLs correspond to the stimulated response by the simulated virus, which lasts beyond the viral challenge. (i), An IgG isotype shows a substantial response to the viral challenge, with subtype IgG1 most notably responding. (j), The CD4+ TLs population is globally stimulated; the memory response results in consolidation, which increases cell numbers and is still available over 100 days after the viral challenge. (k), The population of memory CD8+ cells is stimulated by the viral challenge, acting directly on viral clearance. Full article ">

17 pages, 2905 KiB

Open AccessArticle

Maximization of Open Hospital Capacity under Shortage of SARS-CoV-2 Vaccines—An Open Access, Stochastic Simulation Tool

by Wolfram A. Bosbach, Martin Heinrich, Rainer Kolisch and Christian Heiss

Vaccines 2021, 9(6), 546; https://doi.org/10.3390/vaccines9060546 - 22 May 2021

Cited by 7 | Viewed by 3006

Abstract

Motive. The Covid-19 pandemic has led to the novel situation that hospitals must prioritize staff for a vaccine rollout while there is acute shortage of the vaccine. In spite of the availability of guidelines from state agencies, there is partial confusion about what [...] Read more.

Motive. The Covid-19 pandemic has led to the novel situation that hospitals must prioritize staff for a vaccine rollout while there is acute shortage of the vaccine. In spite of the availability of guidelines from state agencies, there is partial confusion about what an optimal rollout plan is. This study investigates effects in a hospital model under different rollout schemes. Methods. A simulation model is implemented in VBA, and is studied for parameter variation in a predefined hospital setting. The implemented code is available as open access supplement. Main results. A rollout scheme assigning vaccine doses to staff primarily by staff’s pathogen exposure maximizes the predicted open hospital capacity when compared to a rollout based on a purely hierarchical prioritization. The effect increases under resource scarcity and greater disease activity. Nursing staff benefits most from an exposure focused rollout. Conclusions. The model employs SARS-CoV-2 parameters; nonetheless, effects observable in the model are transferable to other infectious diseases. Necessary future prioritization plans need to consider pathogen characteristics and social factors. Full article

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14 pages, 1421 KiB

Open AccessArticle

Local Sustained GM-CSF Delivery by Genetically Engineered Encapsulated Cells Enhanced Both Cellular and Humoral SARS-CoV-2 Spike-Specific Immune Response in an Experimental Murine Spike DNA Vaccination Model

by Rémi Vernet, Emily Charrier, Erika Cosset, Sabine Fièvre, Ugo Tomasello, Julien Grogg and Nicolas Mach

Vaccines 2021, 9(5), 484; https://doi.org/10.3390/vaccines9050484 - 10 May 2021

Cited by 4 | Viewed by 4072

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with recurrences. Therefore, finding a vaccine for this virus became a priority for the scientific community. The SARS-CoV-2 spike protein has been described as the keystone for viral entry into cells [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with recurrences. Therefore, finding a vaccine for this virus became a priority for the scientific community. The SARS-CoV-2 spike protein has been described as the keystone for viral entry into cells and effective immune protection against SARS-CoV-2 is elicited by this protein. Consequently, many commercialized vaccines focus on the spike protein and require the use of an optimal adjuvant during vaccination. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated a powerful enhancement of acquired immunity against many pathogens when delivered in a sustained and local manner. In this context, we developed an encapsulated cell-based technology consisting of a biocompatible, semipermeable capsule for secretion of GM-CSF. In this study, we investigated whether murine GM-CSF (muGM-CSF) represents a suitable adjuvant for SARS-CoV-2 immunization, and which delivery strategy for muGM-CSF could be most beneficial. To test this, different groups of mice were immunized with intra-dermal (i.d.) electroporated spike DNA in the absence or presence of recombinant or secreted muGM-CSF. Results demonstrated that adjuvanting a spike DNA vaccine with secreted muGM-CSF resulted in enhancement of specific cellular and humoral immune responses against SARS-CoV-2. Our data also highlighted the importance of delivery strategies to the induction of cellular and humoral-mediated responses. Full article

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Vaccination Strategy. (A). Vaccination scheme. Three groups of 12 mice were immunized at Day 0 by an intradermal injection of DNA plasmid coding for SARS-CoV-2 spike protein. For two groups, the immunization was adjuvanted either with recombinant muGM-CSF or with muGM-CSF secreted by encapsulated cells. On the day of immunization, a submandibular blood puncture was performed for baseline serum isolation. On Days 10 and 28, 5 mice per group were sacrificed to assess T Cell and B Cell responses. At Day 28, the 2 remaining mice per group received a boost DNA spike plasmid injection and were kept until Day 56 for B Cell responses assessment. (B). Dermal SARS-CoV-2 Spike protein expression by western blot analysis. Skin punch biopsies were taken at the site of intradermal injection from all animals, digested, and analyzed by western blot for the presence of the SARS-CoV-2 spike protein. Three randomly selected mice per time points are represented. (C). muGM-CSF Adjuvant quantification by ELISA. The muGM-CSF secreted by encapsulated cells was quantified by ELISA before and after implantation in mice. **** p < 0.0001. Full article ">Figure 2
TNF-α and IFN-γ production by CD8+ T cells 10 days after vaccination. Mice were immunized with a single dose of spike DNA plasmid with or without GM-CSF (recombinant or secreted by encapsulated cells) as an adjuvant. T cells response was measured at Day 10 by intracellular cytokine staining (ICS) after stimulation of splenocytes with spike protein peptide pools or DMSO as a negative control. Data show the percentage of TNF-α or IFN-γ-secreting CD8+ T cells after stimulation. Data are represented as min-to-max boxes with individual values. ** p < 0.01, *** p < 0.001, and **** p < 0.0001. Full article ">Figure 3
Polyfunctionality of Spike-specific CD8+ T cells at day 10 post-vaccination. (A). Histogram representing the percentage of functional CD8+ T cells with 1, 2, 3, 4 or 5 functions after pool 1 and pool 2 stimulation. (B). Pie charts representing the proportion of responding CD8+ T cells expressing different combinations of cytokines and degranulation markers after stimulation with spike peptide pool 1 or pool 2, PMA/ionomycin (positive control) or DMSO (negative control) stimulation. Histograms and Pie charts represents the mean of 5 animals per group. Full article ">Figure 4
Cytokines profile of spike-specific CD4+ T cells 10 and 28 days after vaccination. Mice were immunized with a single dose of spike DNA plasmid with or without GM-CSF (recombinant or secreted by encapsulated cells) as an adjuvant. T cells responses were measured at day 10 and 28 by intracellular cytokines staining (ICS) after stimulation of splenocyte with spike protein peptide pools or DMSO as a negative control. Data show the percentage of cytokines secreting CD4+ T cells after stimulation. Data show the percentage of responding CD4+ T cells after stimulation. Data are represented as min-to-max boxes with individual values. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. Full article ">Figure 5
Antibodies against SARS-CoV-2 Spike Protein Detected by ELISA.Mice were immunized with a single dose of spike DNA plasmid with or without GM-CSF (recombinant or secreted by encapsulated cells) as an adjuvant. B cell response was measured at day 10 and 28 by quantification of the serum’s antibodies. (A). IgG, IgM, IgA against SARS CoV2 Spike Protein. Day 10, p value * = 0.0324; Day 28, p value * = 0.0277; Day 56, p value **** < 0.0001. (B). IgG against SARS CoV2 Spike Protein. Day 10, p value * = 0.0162; Day 28, p value ** = 0.0089; Day 56, p value **** < 0.0001. Fold change is calculated between the baseline and the day of sacrifice values. Data analysis are represented with geometric means with geometric SD. Full article ">

8 pages, 517 KiB

Open AccessArticle

Sensitivity to COVID-19 Vaccine Effectiveness and Safety in Shanghai, China

by Jia Lu, Xiaosa Wen, Qi Guo, Mengdi Ji, Felicia Zhang, Abram L. Wagner and Yihan Lu

Vaccines 2021, 9(5), 472; https://doi.org/10.3390/vaccines9050472 - 7 May 2021

Cited by 24 | Viewed by 4645

Abstract

Several COVID-19 vaccines have been on the market since early 2021 and may vary in their effectiveness and safety. This study characterizes hesitancy about accepting COVID-19 vaccines among parents in Shanghai, China, and identifies how sensitive they are to changes in vaccine safety [...] Read more.

Several COVID-19 vaccines have been on the market since early 2021 and may vary in their effectiveness and safety. This study characterizes hesitancy about accepting COVID-19 vaccines among parents in Shanghai, China, and identifies how sensitive they are to changes in vaccine safety and effectiveness profiles. Schools in each township of Minhang District, Shanghai, were sampled, and parents in the WeChat group of each school were asked to participate in this cross-sectional Internet-based survey. Parents responded to questions about hesitancy and were given information about five different COVID-19 vaccine candidates, the effectiveness of which varied between 50 and 95% and which had a risk of fever as a side effect between 5 and 20%. Overall, 3673 parents responded to the survey. Almost 90% would accept a vaccine for themselves (89.7%), for their child (87.5%) or for an elderly parent (88.5%) with the most ideal attributes (95% effectiveness with 5% risk of fever). But with the least ideal attributes (50% effectiveness and a 20% risk of fever) these numbers dropped to 33.5%, 31.3%, and 31.8%, respectively. Vaccine hesitancy, age at first child’s birth, and relative income were all significantly related to sensitivity to vaccine safety and effectiveness. Parents showed a substantial shift in attitudes towards a vaccine based on its safety and effectiveness profile. These findings indicate that COVID-19 vaccine acceptance may be heavily influenced by how effective the vaccine actually is and could be impeded or enhanced based on vaccines already on the market. Full article

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16 pages, 528 KiB

Open AccessArticle

Attitudes of Patients with Cancer towards Vaccinations—Results of Online Survey with Special Focus on the Vaccination against COVID-19

by Anna Brodziak, Dawid Sigorski, Małgorzata Osmola, Michał Wilk, Angelika Gawlik-Urban, Joanna Kiszka, Katarzyna Machulska-Ciuraj and Paweł Sobczuk

Vaccines 2021, 9(5), 411; https://doi.org/10.3390/vaccines9050411 - 21 Apr 2021

Cited by 64 | Viewed by 7865

Abstract

Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions [...] Read more.

Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions and attitudes toward vaccination, we conducted an anonymous online survey among Polish patients diagnosed with cancer. We analyzed how socio-demographic factors, type of cancer, comorbidities, previous influenza vaccinations, and information sources affect the general willingness and opinions about vaccinations, emphasizing vaccination against COVID-19. Six hundred thirty-five patients (80.2% female) participated in the study. A positive attitude towards vaccination was presented by 73.7%, neutral by 17.8%, while negative by 8.5%. Willingness to get vaccinated was declared by 60.3%, 23.5% were unwilling, and 16.2% were undecided. Significant predictors of willingness were education, marital status, active anti-cancer treatment, previous influenza vaccination, and positive attitude towards vaccinations. Patients with cancer have concerns regarding safety, effectiveness, and the process of development of the COVID-19 vaccine. Overall, patients with cancer present positive attitudes towards COVID-19 vaccination but required sufficient information on its efficacy and side effects. Full article

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8 pages, 245 KiB

Open AccessArticle

Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database

by Mansour Tobaiqy, Hajer Elkout and Katie MacLure

Vaccines 2021, 9(4), 393; https://doi.org/10.3390/vaccines9040393 - 16 Apr 2021

Cited by 71 | Viewed by 16096

Abstract

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford–AstraZeneca vaccine amid [...] Read more.

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford–AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization’s assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford–AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity. Full article

12 pages, 545 KiB

Open AccessArticle

Enhancing COVID-19 Vaccines Acceptance: Results from a Survey on Vaccine Hesitancy in Northern Italy

by Chiara Reno, Elisa Maietti, Maria Pia Fantini, Elena Savoia, Lamberto Manzoli, Marco Montalti and Davide Gori

Vaccines 2021, 9(4), 378; https://doi.org/10.3390/vaccines9040378 - 13 Apr 2021

Cited by 119 | Viewed by 13251

Abstract

In March 2021, the coronavirus disease 2019 (COVID-19) pandemic still poses a threat to the global population, and is a public health challenge that needs to be overcome. Now more than ever, action is needed to tackle vaccine hesitancy, especially in light of [...] Read more.

In March 2021, the coronavirus disease 2019 (COVID-19) pandemic still poses a threat to the global population, and is a public health challenge that needs to be overcome. Now more than ever, action is needed to tackle vaccine hesitancy, especially in light of the availability of effective and safe vaccines. A cross-sectional online survey was carried out on a representative random sample of 1011 citizens from the Emilia-Romagna region, in Italy, in January 2021. The questionnaire collected information on socio-demographics, comorbidities, past vaccination refusal, COVID-19-related experiences, risk perception of infection, and likelihood to accept COVID-19 vaccination. Multiple logistic regression analyses and classification tree analyses were performed to identify significant predictors of vaccine hesitancy and to distinguish groups with different levels of hesitancy. Overall, 31.1% of the sample reported hesitancy. Past vaccination refusal was the key discriminating variable followed by perceived risk of infection. Other significant predictors of hesitancy were: ages between 35 and 54 years, female gender, low educational level, low income, and absence of comorbidities. The most common concerns about the COVID-19 vaccine involved safety (54%) and efficacy (27%). Studying the main determinants of vaccine hesitancy can help with targeting vaccination strategies, in order to gain widespread acceptance—a key path to ensure a rapid way out of the current pandemic emergency. Full article

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15 pages, 5082 KiB

Open AccessArticle

Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

by Yong Bok Seo, You Suk Suh, Ji In Ryu, Hwanhee Jang, Hanseul Oh, Bon-Sang Koo, Sang-Hwan Seo, Jung Joo Hong, Manki Song, Sung-Joo Kim and Young Chul Sung

Vaccines 2021, 9(4), 307; https://doi.org/10.3390/vaccines9040307 - 24 Mar 2021

Cited by 25 | Viewed by 6340

Abstract

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only [...] Read more.

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2. Full article

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Diagram and immunogenicity of SARS-CoV-2 DNA vaccines. Schematic diagram of COVID-19 DNA vaccine expressing soluble SARS-CoV-2 S protein (SΔTM) or full-length SARS-CoV-2 S protein (S) (a). BALB/c mice (n = 4–10/group) were immunized at weeks 0 and 2 with pGX27-SΔTM, pGX27-S, or pGX27 (empty control vector) as described in the Methods. Sera were collected at 2 weeks post-prime (blue) and 2 weeks post-boost (red) and evaluated for SARS-CoV-2 S-specific IgG antibodies (b). All data are represented as individual values. ** p < 0.01 as determined by the Mann–Whitney test. Full article ">Figure 2
GX-19 elicits robust binding and neutralizing antibody responses in mice. BALB/c mice (n = 4–7/group) were immunized at weeks 0 and 2 with indicated doses of GX-19 or pGX27 as described in the Methods (a–c). Sera were collected at 2 weeks post-prime (blue) and 2 weeks post-boost (red) and assessed for SARS-CoV-2 S-specific IgG antibodies by ELISA (a), and for post-boost sera, neutralizing antibodies against SARS-CoV-2 live virus (c). Bronchoalveolar lavages (BALs) were collected at 2 weeks post-boost and assayed for SARS-CoV-2 S-specific IgG antibodies by ELISA (b). Data representative of two independent experiments. All data are represented as individual values. * p < 0.05, ** p < 0.01 as determined by the Mann–Whitney test. Full article ">Figure 2 Cont.
GX-19 elicits robust binding and neutralizing antibody responses in mice. BALB/c mice (n = 4–7/group) were immunized at weeks 0 and 2 with indicated doses of GX-19 or pGX27 as described in the Methods (a–c). Sera were collected at 2 weeks post-prime (blue) and 2 weeks post-boost (red) and assessed for SARS-CoV-2 S-specific IgG antibodies by ELISA (a), and for post-boost sera, neutralizing antibodies against SARS-CoV-2 live virus (c). Bronchoalveolar lavages (BALs) were collected at 2 weeks post-boost and assayed for SARS-CoV-2 S-specific IgG antibodies by ELISA (b). Data representative of two independent experiments. All data are represented as individual values. * p < 0.05, ** p < 0.01 as determined by the Mann–Whitney test. Full article ">Figure 3
Immunization with GX-19 elicits Th1-biased T cell responses in mice. BALB/c mice (n = 3–7/group) were immunized at weeks 0 and 2 with indicated doses of GX-19 or pGX27 (empty control vector) as described in the Methods (a–c). Sera were collected at 2 weeks post-boost and assessed for SARS-CoV-2 S-specific IgG1 and IgG2a/b. Endpoint titers (a), and endpoint tier ratios of IgG2a/b to IgG1 (b) were calculated. At 2 weeks post-boost, mouse splenocytes were isolated and re-stimulated with peptide pools spanning the SARS-CoV-2 S protein ex vivo. Indicated cytokines in the supernatants of culture were quantified using a Th1/Th2 cytometric bead array kit. Mean value of the medium alone background (mean ± s.d., pg ml−1) was 19.17 ± 8.61 for IFN-γ, 57.12 ± 6.53 for TNF-α, 33.10 ± 6.72 for IL-2, 7.83 ± 0.45 for IL-4, and 4.66 ± 0.13 for IL-5 (d). T cell responses were measured by IFN-γ ELISPOT in splenocytes stimulated with peptide pools spanning the SARS-CoV-2 S protein. Shown are spot-forming cells (SFC) per 106 splenocytes (c). Cells were stained for intracellular production of IFN-γ, TNF-α, and IL-2. Shown are the frequency of S-specific CD4+ or CD8+ T cells after subtraction of background (DMSO vehicle, Sigma-Aldrich, St. Louis, MO, USA) (e). Data representative of two independent experiments. All data are represented as individual values. * p < 0.05, ** p < 0.01 as determined by the Mann–Whitney test. Full article ">Figure 4
Antibody and T cell responses after GX-19 vaccination in macaques. Macaques (n = 3) were immunized with 3 mg of GX-19 as described in the Methods. Serum and PBMCs (peripheral blood mononuclear cells) were collected before (week 0), during (week 4 and 5.5), and after (week 8) vaccination and were assessed for SARS-CoV-2 S-specific IgG antibodies by ELISA (a) and neutralizing antibodies against SARS-CoV-2 live virus (b). Data represent mean SEM of individual macaques (GX-19 #1, GX-19 #2, GX-19 #3), and dashed line indicates the assay limits of detection. The number of SARS-CoV-2 S-specific IFN-γ-secreting cells in PBMCs was determined by IFN-γ ELISPOT assay after stimulation with peptide pools spanning the SARS-CoV-2 S protein. Shown are spot-forming cells (SFC) per 106 PBMCS in triplicate wells (c). The frequency of S-specific CD4+ or CD8+ T cells producing IFN-γ, TNF-α, or IL-2 was determined by intracellular cytokine staining assays stimulated with SARS-CoV-2 S peptide pools. Shown are the frequency of S-specific CD4+ or CD8+ T cells after subtraction of background (DMSO vehicle) (d). Data of (a,b,d) are represented as individual values. p-Values determined by the Wilcoxon matched-pairs signed rank test; p-values are shown. Full article ">Figure 5
Protective efficacy of GX-19 against SARS-CoV-2 challenge. Non-vaccinated (n = 3, blue) and GX-19-vaccinated macaques (n = 3, red) were challenged by intratracheal, oral, conjunctival, intranasal, and intravenous administration of 2.7 × 107 TCID50 SARS-CoV-2. Viral load was assessed in nasal swab (a) and throat swab (b) at multiple time points following challenge. Summary of peak viral loads and viral load area under the curve (AUC) in nasal swab (c,e) and throat swab (d,f) following challenge. Dashed line indicates the assay limit of detection. Histopathological changes in the lungs of SARS-CoV-2-challenged macaques (g). Interstitial pneumonia score by microscopic evaluation (n = 6 lung lobes of each animal per group) (h). The lung tissue sections were stained with hematoxylin and eosin (H&E). Data of (a–f) are represented as individual values. Data of (h) is represented as 6 lung lobes of each animal per group. p-Values determined by the Mann–Whitney test; p-values are shown * p < 0.05 as determined by the Mann–Whitney test. Full article ">

11 pages, 252 KiB

Open AccessArticle

Acceptance of a COVID-19 Vaccine in Japan during the COVID-19 Pandemic

by Masaki Machida, Itaru Nakamura, Takako Kojima, Reiko Saito, Tomoki Nakaya, Tomoya Hanibuchi, Tomoko Takamiya, Yuko Odagiri, Noritoshi Fukushima, Hiroyuki Kikuchi, Shiho Amagasa, Hidehiro Watanabe and Shigeru Inoue

Vaccines 2021, 9(3), 210; https://doi.org/10.3390/vaccines9030210 - 3 Mar 2021

Cited by 206 | Viewed by 19041

Abstract

Vaccination could be a key protective measure against coronavirus disease 2019 (COVID-19), and it is important to understand the acceptability of the COVID-19 vaccine among the general public. However, there is no study on the acceptance of a COVID-19 vaccine in Japan. Therefore, [...] Read more.

Vaccination could be a key protective measure against coronavirus disease 2019 (COVID-19), and it is important to understand the acceptability of the COVID-19 vaccine among the general public. However, there is no study on the acceptance of a COVID-19 vaccine in Japan. Therefore, this study aimed to describe the COVID-19 vaccine acceptance and hesitancy situation in Japan and assess the factors associated with such issues. This was a cross-sectional study based on an internet survey completed by 2956 people. Participants were asked to indicate how likely they were to get vaccinated for COVID-19. In addition, the participants responded to questions regarding sociodemographic factors, attitudes, and beliefs regarding COVID-19 infection and vaccination. The proportion of participants with a high likelihood of getting a COVID-19 vaccine was 62.1%. Multiple logistic regression analysis showed that vaccine acceptance was lower among several sociodemographic groups, such as women, adults aged 20–49 years, and those with a low-income level. Several psychological factors, especially the perceived effectiveness of the COVID-19 vaccine, and willingness to protect others by getting oneself vaccinated, were associated with vaccine acceptance. Our results indicate that the perceived effectiveness of the vaccine and willingness to protect others may play an important role in the acceptance of the COVID-19 vaccine. Full article

8 pages, 558 KiB

Open AccessReview

Are We Ready for the Arrival of the New COVID-19 Vaccinations? Great Promises and Unknown Challenges Still to Come

by Davide Gori, Chiara Reno, Daniel Remondini, Francesco Durazzi and Maria Pia Fantini

Vaccines 2021, 9(2), 173; https://doi.org/10.3390/vaccines9020173 - 18 Feb 2021

Cited by 15 | Viewed by 5294

Abstract

While the SARS-CoV-2 pandemic continues to strike and collect its death toll throughout the globe, as of 31 January 2021, the vaccine candidates worldwide were 292, of which 70 were in clinical testing. Several vaccines have been approved worldwide, and in particular, three [...] Read more.

While the SARS-CoV-2 pandemic continues to strike and collect its death toll throughout the globe, as of 31 January 2021, the vaccine candidates worldwide were 292, of which 70 were in clinical testing. Several vaccines have been approved worldwide, and in particular, three have been so far authorized for use in the EU. Vaccination can be, in fact, an efficient way to mitigate the devastating effect of the pandemic and offer protection to some vulnerable strata of the population (i.e., the elderly) and reduce the social and economic burden of the current crisis. Regardless, a question is still open: after vaccination availability for the public, will vaccination campaigns be effective in reaching all the strata and a sufficient number of people in order to guarantee herd immunity? In other words: after we have it, will we be able to use it? Following the trends in vaccine hesitancy in recent years, there is a growing distrust of COVID-19 vaccinations. In addition, the online context and competition between pro- and anti-vaxxers show a trend in which anti-vaccination movements tend to capture the attention of those who are hesitant. Describing this context and analyzing its possible causes, what interventions or strategies could be effective to reduce COVID-19 vaccine hesitancy? Will social media trend analysis be helpful in trying to solve this complex issue? Are there perspectives for an efficient implementation of COVID-19 vaccination coverage as well as for all the other vaccinations? Full article

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