Vaccines

15 pages, 2462 KiB

Open AccessArticle

Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System

by Bruno Corsini, Leire Aguinagalde, Susana Ruiz, Mirian Domenech and Jose Yuste

Vaccines 2021, 9(2), 186; https://doi.org/10.3390/vaccines9020186 - 23 Feb 2021

Cited by 6 | Viewed by 3270

Abstract

The emergence of non-vaccine serotypes of Streptococcus pneumoniae after the use of vaccines based in capsular polysaccharides demonstrates the need of a broader protection vaccine based in protein antigens and widely conserved. In this study, we characterized three important virulence factors of S. [...] Read more.

The emergence of non-vaccine serotypes of Streptococcus pneumoniae after the use of vaccines based in capsular polysaccharides demonstrates the need of a broader protection vaccine based in protein antigens and widely conserved. In this study, we characterized three important virulence factors of S. pneumoniae namely LytA, LytC, and Pce as vaccine candidates. These proteins are choline-binding proteins that belong to the cell wall hydrolases’ family. Immunization of mice with LytA, LytC, or Pce induced high titers of immunoglobulins G (IgGs) of different subclasses, with IgG1, IgG2a, and IgG2b as the predominant immunoglobulins raised. These antibodies activated the classical pathway of the complement system by increasing the recognition of C1q on the surface of pneumococcal strains of different serotypes. Consequently, the key complement component C3 recognized more efficiently these strains in the presence of specific antibodies elicited by these proteins, activating, therefore, the phagocytosis. Finally, a mouse sepsis model of infection was established, confirming that vaccination with these proteins controlled bacterial replication in the bloodstream, increasing the survival rate. Overall, these results demonstrate that LytA, LytC, and Pce can be protein antigens to be contained in a future universal vaccine against S. pneumoniae. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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Figure 1
Antibody levels in sera after immunization of mice with Alum or different cell wall hydrolases (LytA, LytC, or Pce) mixed in Alum including total IgG (A), IgG1 (B), IgG2a (C), IgG2b (D), and IgG3 (E). Specific antibodies were measured in NMS (gray circles), pooled sera from mice immunized with Alum as adjuvant (black squares) and pooled sera from mice immunized with 20 µg of LytA-Alum (blue triangles), LytC-Alum (red circles), or Pce-Alum (purple diamonds). Error bars represent the SDs and asterisks indicate statistical significance of immunization of each protein compared to the Alum group; * p < 0.05; ** p < 0.01; *** p < 0.001. Full article ">Figure 2
Classical pathway activation mediated by antibodies against LytA, LytC, or Pce. These assays measured deposition of mouse C1q on the surface of the corresponding bacterial strain using pooled sera from mice immunized with Alum (black bars) or with LytA-Alum (blue bars), LytC-Alum (red bars), or Pce-Alum (purple bars). (A) Strain 48 (serotype 23F). (B) Strain 69 (serotype 19F). (C) Strain 450 (serotype 11A). (D) Strain 957 (serotype 3). (E) Example of a flow cytometry histogram for C1q deposition on the serotype 23F strain. Results are expressed as a relative % fluorescence index (% RFI). Error bars represent the SDs and asterisks indicate statistical significance of LytA, LytC, or Pce immunization compared to the Alum group; ** p < 0.01; *** p < 0.001. Full article ">Figure 3
Recognition of different pneumococcal serotypes by C3 mediated by antibodies to LytA, LytC, or Pce. The different strains were exposed to pooled sera from mice immunized with Alum (black bar) or with LytA-Alum (blue bars), LytC-Alum (red bars), or Pce-Alum (purple bars). (A) Strain 48 (serotype 23F). (B) Strain 69 (serotype 19F). (C) Strain 450 (serotype 11A). (D) Strain 957 (serotype 3). (E) Example of a flow cytometry histogram for C1q deposition on the serotype 23F strain. Results are expressed as % RFI. Error bars represent the SDs and asterisks indicate statistical significance of LytA, LytC, or Pce immunization compared to the Alum group; * p < 0.05; ** p < 0.01; *** p < 0.001. Full article ">Figure 4
OP assays using the HL-60 neutrophil cell line and S. pneumoniae strains incubated with HBSS (white bar) or pooled sera from mice immunized with Alum (black bar) or with LytA-Alum (blue bars), LytC-Alum (red bars), or Pce-Alum (purple bars). (A) Strain 48 (serotype 23F). (B) Strain 69 (serotype 19F). (C) Strain 450 (serotype 11A). (D) Strain 957 (serotype 3). (E) Example of a flow cytometry histogram for OP of the clinical isolate of serotype 23F. Results are expressed as % RFI. Error bars represent the SDs and asterisks indicate statistical significance of LytA, LytC, or Pce immunization compared to the Alum group; * p < 0.05; ** p < 0.01; *** p < 0.001. Full article ">Figure 5
Protection mediated by LytA, LytC, or Pce against pneumococcal sepsis caused by strain 48 (serotype 23F). Mice were vaccinated with Alum or with 20 µg of the specific protein (LytA, LytC, or Pce) mixed with Alum. (A) Survival in mice vaccinated with Alum (black line) or LytA-Alum (blue line). (B) Survival in mice vaccinated with Alum (black line) or LytC-Alum (red line). (C) Survival in mice vaccinated with Alum (black line) or Pce-Alum (purple line). (D) Bacterial counts in blood at 24 h from mice immunized with Alum or proteins (LytA, LytC, or Pce) mixed with Alum. Error bars represent the SDs and asterisks indicate statistical significance of vaccination with LytA, LytC, or Pce compared to the Alum group; * p < 0.05. Full article ">

16 pages, 639 KiB

Open AccessReview

Commercial PRRS Modified-Live Virus Vaccines

by Chanhee Chae

Vaccines 2021, 9(2), 185; https://doi.org/10.3390/vaccines9020185 - 22 Feb 2021

Cited by 65 | Viewed by 6466

Abstract

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) presents one of the challenging viral pathogens in the global pork industry. PRRS is characterized by two distinct clinical presentations; reproductive failure in breeding animals (gilts, sows, and boars), and respiratory disease in growing pigs. [...] Read more.

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) presents one of the challenging viral pathogens in the global pork industry. PRRS is characterized by two distinct clinical presentations; reproductive failure in breeding animals (gilts, sows, and boars), and respiratory disease in growing pigs. PRRSV is further divided into two species: PRRSV-1 (formerly known as the European genotype 1) and PRRSV-2 (formerly known as the North American genotype 2). A PRRSV-2 modified-live virus (MLV) vaccine was first introduced in North America in 1994, and, six years later, a PRRSV-1 MLV vaccine was also introduced in Europe. Since then, MLV vaccination is the principal strategy used to control PRRSV infection. Despite the fact that MLV vaccines have shown some efficacy, they were problematic as the efficacy of vaccine was often unpredictable and depended highly on the field virus. This paper focused on the efficacy of commercially available MLV vaccines at a global level based on respiratory disease in growing pigs, and maternal and paternal reproductive failure in breeding animals. Full article

(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)

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14 pages, 7939 KiB

Open AccessArticle

TLR4 Agonist Combined with Trivalent Protein JointS of Streptococcus suis Provides Immunological Protection in Animals

by Zhaofei Wang, Mengting Guo, Licheng Kong, Ya Gao, Jingjiao Ma, Yuqiang Cheng, Henan Wang, Yaxian Yan and Jianhe Sun

Vaccines 2021, 9(2), 184; https://doi.org/10.3390/vaccines9020184 - 22 Feb 2021

Cited by 8 | Viewed by 2689

Abstract

Streptococcus suis (S. suis) serotype 2 (SS2) is the causative agent of swine streptococcosis and can cause severe diseases in both pigs and humans. Although the traditional inactive vaccine can protect pigs from SS2 infection, novel vaccine candidates are needed to [...] Read more.

Streptococcus suis (S. suis) serotype 2 (SS2) is the causative agent of swine streptococcosis and can cause severe diseases in both pigs and humans. Although the traditional inactive vaccine can protect pigs from SS2 infection, novel vaccine candidates are needed to overcome its shortcomings. Three infection-associated proteins in S. suis—muramidase-released protein (MRP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and DLD, a novel putative dihydrolipoamide dehydrogenase—have been previously identified by immunoproteomic assays. In this study, the effective immune protection of the recombinant trivalent protein GAPDH-MRP-DLD (JointS) against SS2, SS7, and SS9 was determined in zebrafish. To improve the immune efficacy of JointS, monophosphoryl lipid A (MPLA) as a TLR4 agonist adjuvant, which induces a strong innate immune response in the immune cells of mice and pigs, was combined with JointS to immunize the mice. The results showed that immunized mice could induce the production of a high titer of anti-S. suis antibodies; as a result, 100% of mice survived after SS2 infection. Furthermore, JointS provides good protection against virulent SS2 strain infections in piglets. Given the above, there is potential to develop JointS as a novel subunit vaccine for piglets to prevent infection by SS2 and other S. suis serotypes. Full article

(This article belongs to the Special Issue Controlled Clinical Evaluation of Veterinary Vaccines)

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Figure 1
Kaplan–Meier survival curves of vaccinated zebrafish infected with different serotypes of S. suis. Seven days after booster immunization, SS2, SS7, or SS9 were injected into the abdominal cavities of the zebrafish. PBS-vaccinated zebrafish infected with S. suis served as PBS control groups. Survival rate was analyzed by a log-rank (Mantel-Cox) test. Full article ">Figure 2
MPLA- and R837-induced cytokine expression in RAW264.7 and PAM cells. IL-6, IL-8, and IFN-γ levels were measured by qRT-PCR. Untreated cells served as the control. Levels of IL-6, IL-8, and IFN-γ mRNA were normalized to the mRNA levels of the reference gene; they were then expressed as n-fold increases with respect to the untreated cells (0 μg of MPLA or R837). Kruskal Wallis test followed by Dunn’s post-hoc test was used to compare the results between the different treated groups and controls. *** p < 0.001, ** p < 0.01, * p < 0.05, and ns (p > 0.05). Error bars represent SEM. Full article ">Figure 3
MPLA combined with JointS to prevent S. suis infection in mice antibody titer (A), cytokine levels (B), immune protection rates (C), clinical score (D), and colony forming unit (CFU) burdens in the blood or tissues (E–G) in the differently vaccinated groups after challenge by HA9801. The mice were immunized by JointS protein formulated with Freund’s adjuvant (JointS + CFA/IFA), R837 (JointS + R837), or MPLA (JointS + MPLA). The mice immunized by inactivated SS2 (HA9801) strains formulated with MPLA were termed inactivated SS2 + MPLA. The PBS-immunized mice served as the control group. After 28 days, a lethal dose (5 × 108 CFU/mouse) of SS2 was injected into the abdominal cavities of the mice. Survival rates and clinical signs were monitored for seven days post-infection. In (A), Kruskal Wallis test followed by Dunn’s post-hoc test showed that the antibody titers in the immunized mice were significantly higher than in the non-immunized mice. In (B), an unpaired Student’s t-test showed that the cytokine levels in the groups administered antigens formulated with MPLA were significantly higher than in the groups administered JointS formulated with Freund’s adjuvant or R837. In (C), survival rates were analyzed by a log-rank (Mantel–Cox) test. In (D), Kruskal Wallis test followed by Dunn’s post-hoc test showed that the clinical score in the immunized mice were significantly lower than in the non-immunized mice. In (E–G), an unpaired Student’s t-test showed that the CFU burdens in the groups administered antigens formulated with MPLA were significantly lower than in the groups administered JointS formulated with Freund’s adjuvant or R837. Samples collected from each mouse were tested in triplicate. *** p < 0.001, ** p < 0.01, * p < 0.05, and ns (p > 0.05). The error bars represent SEM. Full article ">Figure 4
Antibody titers in the vaccinated piglets. Antibody titers were tested by ELISA using inactivated SS2 (A) or purified GAPDH, MRP, and DLD proteins (B) with immunized sera. Samples collected from each piglet were tested in triplicate. In (A), an unpaired Student’s t-test showed the antibody titers in the JointS immunized mice were significantly higher than PBS-immunized mice in different time points. In (B), Kruskal Wallis test followed by Dunn’s post-hoc test showed the specific antibody titers against GAPDH were significantly lower than MRP, DLD, or JointS. *** p < 0.001 and ** p < 0.01. The error bars represent SEM. Full article ">Figure 5
Clinical score (A), rectal temperature (B), and body weight (C) in the vaccinated piglets after the challenge with SS2. Signs of rectal temperature and body weight were monitored for 7 d post-infection. In (A), an unpaired Student’s t-test showed that the clinical score in the immunized piglets was significantly lower than in PBS-immunized piglets. In (B), recovery was indicated at a rectal temperature below 39.5 °C. In (C), an unpaired Student’s t-test showed that daily gain of body weight in the immunized piglets was significantly higher than in the PBS-immunized piglets. Samples collected from each piglet were tested in triplicate. *** p < 0.001, ** p < 0.01, * p < 0.05, and ns (p > 0.05). The error bars represent SEM. Full article ">

10 pages, 248 KiB

Open AccessArticle

Enhancement of Vaccination Attitude and Flu Vaccination Coverage among Pregnant Women Attending Birthing Preparation Course

by Stefania Bruno, Brigida Carducci, Gianluigi Quaranta, Viria Beccia, Andrea Di Pilla, Daniele Ignazio La Milia, Marcello Di Pumpo, Elettra Carini, Lucia Masini, Enrica Tamburrini, Antonietta Spadea, Gianfranco Damiani, Antonio Lanzone and Patrizia Laurenti

Vaccines 2021, 9(2), 183; https://doi.org/10.3390/vaccines9020183 - 21 Feb 2021

Cited by 4 | Viewed by 2480

Abstract

Most vaccinations are recommended within the 15th month of life, in order to reduce risks and to protect children from the initial stages of their lives. A vaccination training session was carried out during the birthing preparation course, aimed at increasing the attitude [...] Read more.

Most vaccinations are recommended within the 15th month of life, in order to reduce risks and to protect children from the initial stages of their lives. A vaccination training session was carried out during the birthing preparation course, aimed at increasing the attitude toward vaccination in maternal-child age. A questionnaire on vaccination awareness was administered before and after the training session and on-site flu vaccination was offered to women and their companions. The percentage of participants who consider the preparatory course a useful tool to obtain information about vaccines increases significantly from 30.34% at pre-intervention to 64.56% at post-intervention (p < 0.001). There is a significant increase in the mean number of vaccinations that the participants want their children to get. The number of participants believing that there is no relationship between vaccination and autism rose from 41.05 to 72.97% (p < 0.001). In total, 48 out of 119 (40.34%) pregnant women participating in the course and 39 companions were vaccinated for influenza. Vaccination knowledge and attitude significantly increased after a training session dedicated to vaccination as a part of the pregnant pre-birth course, whose aim can be therefore extended to the management of the health of the child, well beyond the period of pregnancy, according to the life-course approach to health. Full article

(This article belongs to the Special Issue Women's Disease and Related Vaccine)

18 pages, 2767 KiB

Open AccessArticle

Protection against Different Genotypes of Newcastle Disease Viruses (NDV) Afforded by an Adenovirus-Vectored Fusion Protein and Live NDV Vaccines in Chickens

by Helena L. Ferreira, Patti J. Miller and David L. Suarez

Vaccines 2021, 9(2), 182; https://doi.org/10.3390/vaccines9020182 - 21 Feb 2021

Cited by 10 | Viewed by 4188

Abstract

The efficacy of an adenovirus-vectored Newcastle disease virus (NDV) vaccine expressing the fusion (F) NDV protein (adeno-F) was evaluated against challenges with virulent heterologous and homologous NDV strains to the F protein. In a preliminary study, two different doses (low and high) of [...] Read more.

The efficacy of an adenovirus-vectored Newcastle disease virus (NDV) vaccine expressing the fusion (F) NDV protein (adeno-F) was evaluated against challenges with virulent heterologous and homologous NDV strains to the F protein. In a preliminary study, two different doses (low and high) of adeno-F were tested against a virulent NDV strain containing the homologous NDV F protein, CA02. In a second study, at three weeks post-vaccination, the efficacy of the high dose of adeno-F was compared to a live attenuated NDV vaccine strain (LaSota) against three antigenically distinct virulent NDV challenge strains, one homologous (CA02) and two heterologous (TZ12, EG14) to F in the vectored vaccine. In both experiments, clinical signs, mortality, virus shedding, and humoral response were evaluated. In the first experiment, the survival rates from birds vaccinated with adeno-F at a high and low dose were 100% and 25%, respectively. In the second experiment, birds vaccinated with the high dose of adeno-F had a survival rate of 80%, 75%, and 65% after challenge with the CA02, TZ12, and EG14 viruses, respectively. All of the LaSota-vaccinated birds survived post-challenge no matter the NDV challenge strain. High antibody titers were detected after vaccination with LaSota by HI and ELISA tests. The majority of adeno-F-vaccinated birds had detectable antibodies using the ELISA test, but not using the HI test, before the challenge. The data show that both the similarity of the F protein of the adeno-F vaccine to the challenge virus and the adeno-F vaccination dose affect the efficacy of an adenovirus-vectored NDV vaccine against a virulent NDV challenge. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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Figure 1
Phylogenetic analysis of challenge strains and amino acid identity of vaccines compared to challenge strains (names highlighted in green and italicized). The evolutionary history was inferred by using the maximum likelihood method based on the general time reversible model [<a href="#B21-vaccines-09-00182" class="html-bibr">21</a>]. The tree with the highest log likelihood (−18,610.06) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. Initial tree(s) for the heuristic search was (were) obtained automatically by applying neighbor joining and BioNJ algorithms to a matrix of pairwise distances estimated using the maximum composite likelihood (MCL) approach and then selecting the topology with a superior log likelihood value. A discrete gamma distribution was used to model evolutionary rate differences among sites (5 categories (+G, parameter = 0.4368)). The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 59 nucleotide sequences. All positions containing gaps and missing data were eliminated. There were a total of 1656 positions in the final dataset. Evolutionary analyses were conducted in MEGA7 [<a href="#B35-vaccines-09-00182" class="html-bibr">35</a>]. Full article ">Figure 2
Survival rates after Newcastle disease virus (NDV) challenge in control and vaccinated birds. (A) Vaccinated birds with the low and high doses of adeno-F and control groups were monitored after NDV challenge with CA02 virus for 14 days. (B) Birds vaccinated with adeno-F and LaSota virus and non-vaccinated birds (control) after NDV challenge with CA02, EG14, and TZ12 viruses for 11 days. Different letters are statistically significant (p < 0.05). Full article ">Figure 2 Cont.
Survival rates after Newcastle disease virus (NDV) challenge in control and vaccinated birds. (A) Vaccinated birds with the low and high doses of adeno-F and control groups were monitored after NDV challenge with CA02 virus for 14 days. (B) Birds vaccinated with adeno-F and LaSota virus and non-vaccinated birds (control) after NDV challenge with CA02, EG14, and TZ12 viruses for 11 days. Different letters are statistically significant (p < 0.05). Full article ">Figure 3
Vaccinated and non-vaccinated birds shed virus after NDV challenge in the different experiments. (A) Oropharyngeal (OP) and cloacal (CL) swabs from birds in the control group and in groups vaccinated with adeno-F at high and low doses were tested by RRT-PCR after 2 and 4 days post-challenge (dpc). (B) Virus shedding from vaccinated birds with LaSota and adeno-F vaccines and non-vaccinated birds in OP and cloacal swabs at 2, 4, and 7 days after challenge with CA02, EG14, or TZ12. Viral titers in OP or CL swab samples from the different treatments (control, adeno-F—low and high doses, and LaSota) on the same day and with the same NDV challenge strain. The mean ± standard errors with different letters (a, b, or c) are statistically significant (p < 0.05). CL: cloacal swab; OP: oropharyngeal swab. Full article ">Figure 3 Cont.
Vaccinated and non-vaccinated birds shed virus after NDV challenge in the different experiments. (A) Oropharyngeal (OP) and cloacal (CL) swabs from birds in the control group and in groups vaccinated with adeno-F at high and low doses were tested by RRT-PCR after 2 and 4 days post-challenge (dpc). (B) Virus shedding from vaccinated birds with LaSota and adeno-F vaccines and non-vaccinated birds in OP and cloacal swabs at 2, 4, and 7 days after challenge with CA02, EG14, or TZ12. Viral titers in OP or CL swab samples from the different treatments (control, adeno-F—low and high doses, and LaSota) on the same day and with the same NDV challenge strain. The mean ± standard errors with different letters (a, b, or c) are statistically significant (p < 0.05). CL: cloacal swab; OP: oropharyngeal swab. Full article ">Figure 4
Antibody titers before and after challenge with CA02 virus. The hemagglutination inhibition (HI) test was performed in sera from non-vaccinated birds and birds vaccinated with adeno-F at low and high doses before and after challenge with CA02. No significant difference was detected comparing all groups before or after challenge. Different letters (a or b) are statistically significant. dpv: days post-vaccination, dpc: days post-challenge. Full article ">Figure 5
Antibody titers before and after challenge with NDV challenge strains. HI and ELISA tests were performed before and after the challenge using the homologous strains (CA02, EG14, and TZ12) in sera from control birds and birds vaccinated with LaSota or adeno-F vaccines. HI or ELISA antibody titers in sera samples from the different treatments (control, adeno-F, and LaSota) and NDV challenge strains were compared. Different letters (a, b or c) are statistically significant (p < 0.05). dpv: days post-vaccination, dpc: days post-challenge. Full article ">

19 pages, 410 KiB

Open AccessReview

Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates

by Julio Sempere, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech and Fernando González-Camacho

Vaccines 2021, 9(2), 181; https://doi.org/10.3390/vaccines9020181 - 20 Feb 2021

Cited by 13 | Viewed by 4171

Abstract

Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal [...] Read more.

Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes (up to 100 different serotypes have been identified) and are unable to protect against non-vaccine serotypes and non-encapsulated pneumococci. The emergence of antibiotic-resistant non-vaccine serotypes after these vaccines is an increasing threat. Therefore, there is an urgent need to develop new pneumococcal vaccines which could cover a wide range of serotypes. One of the vaccines most characterized as a prophylactic alternative to current PPV-23 or PCVs is a vaccine based on pneumococcal protein antigens. The choline-binding proteins (CBP) are found in all pneumococcal strains, giving them the characteristic to be potential vaccine candidates as they may protect against different serotypes. In this review, we have focused the attention on different CBPs as vaccine candidates because they are involved in the pathogenesis process, confirming their immunogenicity and protection against pneumococcal infection. The review summarizes the major contribution of these proteins to virulence and reinforces the fact that antibodies elicited against many of them may block or interfere with their role in the infection process. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

12 pages, 269 KiB

Open AccessArticle

Antibody Response to Canine Parvovirus Vaccination in Dogs with Hypothyroidism Treated with Levothyroxine

by Michèle Bergmann, Monika Freisl, Katrin Hartmann, Stephanie Speck, Uwe Truyen, Yury Zablotski, Matthias Mayr and Astrid Wehner

Vaccines 2021, 9(2), 180; https://doi.org/10.3390/vaccines9020180 - 20 Feb 2021

Cited by 4 | Viewed by 3622

Abstract

(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: [...] Read more.

(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: Six dogs with HypoT and healthy age-matched control dogs (n = 23) were vaccinated against CPV with a modified-live vaccine. Hemagglutination inhibition was used to measure antibodies on days 0, 7, and 28. The comparison of the vaccination response of dogs with HypoT and healthy dogs were performed with univariate analysis. (3) Results: Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HypoT (6/6; 95% CI: 55.7–100) and in 100% of healthy dogs (23/23; 95% CI: 83.1–100.0). A ≥4-fold titer increase was observed in none of the dogs with HypoT and in 4.3% of the healthy dogs (1/23; CI_95%: <0.01–22.7). Mild vaccine-associated adverse events (VAAEs) were detected in 33.3% of the dogs with HypoT (2/6; 95% CI: 9.3–70.4) and in 43.5% (10/23; 95% CI: 25.6–63.2) of the healthy dogs. (4) Conclusions: There was neither a significant difference in the dogs’ pre-vaccination antibodies (p = 1.000), or vaccination response (p = 0.735), nor in the occurrence of post-vaccination VAAEs (p = 0.798). The vaccination response in dogs with levothyroxine-treated HypoT seems to be similar to that of healthy dogs. Full article

(This article belongs to the Special Issue Infectious Diseases Immunology)

23 pages, 1139 KiB

Open AccessReview

Development of Fish Parasite Vaccines in the OMICs Era: Progress and Opportunities

by Saloni Shivam, Mansour El-Matbouli and Gokhlesh Kumar

Vaccines 2021, 9(2), 179; https://doi.org/10.3390/vaccines9020179 - 20 Feb 2021

Cited by 28 | Viewed by 7156

Abstract

Globally, parasites are increasingly being recognized as catastrophic agents in both aquaculture sector and in the wild aquatic habitats leading to an estimated annual loss between 1.05 billion and 9.58 billion USD. The currently available therapeutic and control measures are accompanied by many [...] Read more.

Globally, parasites are increasingly being recognized as catastrophic agents in both aquaculture sector and in the wild aquatic habitats leading to an estimated annual loss between 1.05 billion and 9.58 billion USD. The currently available therapeutic and control measures are accompanied by many limitations. Hence, vaccines are recommended as the “only green and effective solution” to address these concerns and protect fish from pathogens. However, vaccine development warrants a better understanding of host–parasite interaction and parasite biology. Currently, only one commercial parasite vaccine is available against the ectoparasite sea lice. Additionally, only a few trials have reported potential vaccine candidates against endoparasites. Transcriptome, genome, and proteomic data at present are available only for a limited number of aquatic parasites. Omics-based interventions can be significant in the identification of suitable vaccine candidates, finally leading to the development of multivalent vaccines for significant protection against parasitic infections in fish. The present review highlights the progress in the immunobiology of pathogenic parasites and the prospects of vaccine development. Finally, an approach for developing a multivalent vaccine for parasitic diseases is presented. Data sources to prepare this review included Pubmed, google scholar, official reports, and websites. Full article

(This article belongs to the Section Veterinary Vaccines)

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Figure 1
Conceptual representation of multivalent/multiepitope vaccine formulation for fish parasites in the omics era. Analysis of genomic, transcriptomic and proteomic data of parasite and the data obtained from host–parasite interactions enable identifying a suitable antigen as vaccine candidates. Genome sequence contains the entire genetic repertoire of antigens from which novel vaccine targets can be selected. Transcriptome analysis provides insights on the parasite gene expression profile leading to successful establishment and pathology in host. Proteomic analysis provides information on protein expression under specified conditions. It is useful in identification of proteins that are expressed by parasite during infection and the subset of proteins which are present on parasite surface (surface proteome). Surface exposed proteins which are immunogenic in the host can be suitable vaccine candidate. Structural genomics helps to know the three-dimensional structure of proteins produced by an organism and how they interact with antibodies or drugs. Immunoproteomics provides information on the proteins or epitopes which interact with host antibodies. Full article ">Figure 2
Workflow for identification of vaccine candidates and vaccine formulation using high throughput omics techniques. The material of interest (DNA, RNA or protein) can be extracted from the desired parasite or from-infected host fish tissue. The isolated material serves as sample for next generation sequence analysis (for DNA and RNA) and spectrophotometry and Edman sequencing (for protein). The obtained sequences can be subjected to different bioinformatic tools for analysis and functional annotation of parasite molecules. Based on molecular function and biological pathway analysis, the immunogenic targets (capable of eliciting host immune response) can be selected and their protective epitopes predicted. These molecules can then be produced on a large scale and combined with suitable adjuvants to form vaccine. Subsequently, the vaccine thus produced can be used for conducting trials in suitable fish and its efficacy and appropriate route of administration can be determined. Full article ">

12 pages, 1060 KiB

Open AccessReview

Spike S2 Subunit: The Dark Horse in the Race for Prophylactic and Therapeutic Interventions against SARS-CoV-2

by Kim Tien Ng, Nur Khairiah Mohd-Ismail and Yee-Joo Tan

Vaccines 2021, 9(2), 178; https://doi.org/10.3390/vaccines9020178 - 20 Feb 2021

Cited by 22 | Viewed by 4897

Abstract

In the midst of the unceasing COVID-19 pandemic, the identification of immunogenic epitopes in the SARS-CoV-2 spike (S) glycoprotein plays a vital role in the advancement and development of intervention strategies. S is expressed on the exterior of the SARS-CoV-2 virion and contains [...] Read more.

In the midst of the unceasing COVID-19 pandemic, the identification of immunogenic epitopes in the SARS-CoV-2 spike (S) glycoprotein plays a vital role in the advancement and development of intervention strategies. S is expressed on the exterior of the SARS-CoV-2 virion and contains two subunits, namely the N-terminal S1 and C-terminal S2. It is the key element for mediating viral entry as well as a crucial antigenic determinant capable of stimulating protective immune response through elicitation of anti-SARS-CoV-2 antibodies and activation of CD4⁺ and CD8⁺ cells in COVID-19 patients. Given that S2 is highly conserved in comparison to the S1, here, we provide a review of the latest findings on the SARS-CoV-2 S2 subunit and further discuss its potential as an attractive and promising target for the development of prophylactic vaccines and therapeutic agents against COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 Serological Studies around the Globe)

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14 pages, 262 KiB

Open AccessArticle

Botched Ebola Vaccine Trials in Ghana: An Analysis of Discourses in the Media

by Esi E. Thompson

Vaccines 2021, 9(2), 177; https://doi.org/10.3390/vaccines9020177 - 19 Feb 2021

Cited by 7 | Viewed by 2511

Abstract

In June 2015, proposed Ebola vaccine trials were suspended by the Ministry of Health of Ghana amid protests from members of parliament and the general public. Scholarship has often focused on the design, development, and administration of vaccines. Of equal importance are the [...] Read more.

In June 2015, proposed Ebola vaccine trials were suspended by the Ministry of Health of Ghana amid protests from members of parliament and the general public. Scholarship has often focused on the design, development, and administration of vaccines. Of equal importance are the social issues surrounding challenges with vaccine trials and their implementation. The purpose of this study was to analyze discourses in the media that led to the suspension of the 2015 Ebola vaccine trials in Ghana. I use a sociological lens drawing on moral panic and risk society theories. The study qualitatively analyzed discourses in 18 semi-structured interviews with media workers, selected online publications, and user comments about the Ebola vaccine trials. The findings show that discourses surrounding the Ebola vaccine trials drew on cultural, biomedical, historical, and even contextual knowledge and circumstances to concretize risk discourses and garner support for their positions. Historical, political, and cultural underpinnings have a strong influence on biomedical practices and how they are (not) accepted. This study highlights the complexity and challenges of undertaking much needed vaccine tests in societies where the notion of drug trials has underlying historical and sociological baggage that determine whether (or not) the trials proceed. Full article

(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)

18 pages, 1678 KiB

Open AccessReview

HIV-1 Envelope Glycosylation and the Signal Peptide

by Gregory S. Lambert and Chitra Upadhyay

Vaccines 2021, 9(2), 176; https://doi.org/10.3390/vaccines9020176 - 19 Feb 2021

Cited by 7 | Viewed by 3797

Abstract

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in [...] Read more.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design. Full article

(This article belongs to the Special Issue HIV Vaccine)

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Figure 1
Schematic linear representation of the nascent HIV-1 Envelope (Env) protein attached to the HIV-1 signal peptide (SP). (Top) Regions corresponding to SP, glycoprotein 120 (gp120), and glycoprotein 41 (gp41) are indicated. Variable and constant regions of gp120 are indicated by V1-V5 and C1-C5, respectively. SP cleavage site is indicated by an arrow. (Bottom) Expanded schematic representation of the HIV-1 SP. The N-terminal hydrophilic positively charged region is shown in red, the central hydrophobic region is shown in green, and the slightly polar C-terminal region is shown in blue. Full article ">Figure 2
Representative top and side views of Env trimers in state 1 (closed), state 2 (intermediate), and state 3 (open) conformations. Regions corresponding to gp120 (grey), gp41 (orange), V1V2 (yellow), V3 (green), and the CD4 binding site (red) are indicated. Protein Data Bank identifier (PDB ID) numbers are also indicated. Structures adapted from Gristick et al., 2016 [<a href="#B26-vaccines-09-00176" class="html-bibr">26</a>], Bjorkman et al., 2018 [<a href="#B27-vaccines-09-00176" class="html-bibr">27</a>], and Ozorowski et al., 2017 [<a href="#B28-vaccines-09-00176" class="html-bibr">28</a>]. Full article ">Figure 3
N-linked glycans on the HIV-1 envelope (Env). (A) Potential N-linked glycosylation site (PNGS) occupancy is initiated via the placement of a Glc3Man9GlcNAc2 residue, which is subsequently modified during transit through the endoplasmic reticulum (ER) and Golgi by a milieu of host enzymes to yield its final glycoform. Figure adapted from Jan et al., 2019 [<a href="#B49-vaccines-09-00176" class="html-bibr">49</a>]. (B) Crystal structure (2.19 Å) of PG9 mAb in complex with V1V2 region from HIV-1. Regions corresponding to V1V2 (yellow), PG9 (grey), PNGS N156 and N160 (blue), and N-glycans (orange) are indicated. Protein Data Bank identifier (PDB ID) number is also indicated. Adapted from McLellan et al., 2011 [<a href="#B50-vaccines-09-00176" class="html-bibr">50</a>]. Full article ">Figure 4
Effect of signal peptide (SP) modification/replacement on envelope (Env). (A) The HIV-1 SP is responsible for targeting the nascent glycoprotein 160 (gp160) precursor to the endoplasmic reticulum (ER) for processing. Uniquely, the SP remains attached to this protein throughout the ER and is cleaved prior to delivery of gp160 to the Golgi apparatus. Further retention of the SP results in lysosomal degradation of Env and serves as a quality control mechanism. (B) Mutations at specific residues within the N-terminal region of the HIV-1 SP result in alterations to Env expression, glycosylation, DC-SIGN-mediated transinfection, antigenicity, and neutralization. (C, top) Replacement of the native HIV-1 SP with heterologous HIV-1 SPs alters glycosylation, Env recognition by monoclonal antibodies (mAbs), and virus neutralization. Replacement with non-HIV-1 SPs is a common strategy for increasing immunogen yield. However, this approach may also have detrimental effects on Env glycosylation, structure, and antigenicity. The perceived advantage of increased soluble protein yields may be offset by a higher proportion of Env immunogens with under-processed glycans due to the absence of HIV-1 SP-mediated effects on processing. (C, bottom) The glycosylation profiles of HIV-1 glycoprotein 120 (gp120) proteins are dependent on their SPs. Transposition of SPs from HIV-1 species with different proportions of glycan types is sufficient to alter glycosylation profiles. Full article ">

14 pages, 1893 KiB

Open AccessArticle

Assessment of Vaccine Hesitancy to a COVID-19 Vaccine in Cameroonian Adults and Its Global Implication

by Jerome Nyhalah Dinga, Leontine Kouemou Sinda and Vincent P. K. Titanji

Vaccines 2021, 9(2), 175; https://doi.org/10.3390/vaccines9020175 - 19 Feb 2021

Cited by 92 | Viewed by 14787

Abstract

Since the outbreak of COVID-19 in December 2019, no global consensus treatment has been developed and generally accepted for the disease. However, eradicating the disease will require a safe and efficacious vaccine. In order to prepare for the eventual development of a safe [...] Read more.

Since the outbreak of COVID-19 in December 2019, no global consensus treatment has been developed and generally accepted for the disease. However, eradicating the disease will require a safe and efficacious vaccine. In order to prepare for the eventual development of a safe and efficacious COVID-19 vaccine and to enhance its uptake, it is imperative to assess vaccine hesitancy in Cameroonians. After obtaining ethical clearance from the Institutional Review Board of the University of Buea, a questionnaire was administered (May–August 2020) to consenting adults either online or in person. A qualitative thematic analysis was done to analyze the participants’ answers to the open questions. A deductive approach was used, that is, the codes and patterns according to the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) Working Group Matrix of Determinants of vaccine hesitancy. The number of consenting adult Cameroonians who completed the questionnaire were 2512 (Two thousand five hundred and twelve). Vaccine hesitancy to a COVID-19 vaccine was 84.6% in Cameroonians. Using the WHO recommended Matrix of Determinant of Vaccine hesitancy, the most prominent determinants observed in this study were: Communication and Media Environment, Perception of pharmaceutical industry, Reliability and/or source of vaccine and cost. Most Cameroonians agree that even though there are benefits of a clinical trial, they will prefer it should be done out of the continent and involving African scientists for eventual acceptance and uptake. The concerns of safety, efficacy and confidence has to be addressed using a Public Engagement approach if a COVID-19 vaccine has to be administered successfully in Africa or Cameroon specifically. Since this study was carried out following WHO standards, its result can be compared to those of other studies carried out in different cultural settings using similar standards. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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24 pages, 932 KiB

Open AccessReview

Multiple Levels of Immunological Memory and Their Association with Vaccination

by Zsófia Bugya, József Prechl, Tibor Szénási, Éva Nemes, Attila Bácsi and Gábor Koncz

Vaccines 2021, 9(2), 174; https://doi.org/10.3390/vaccines9020174 - 19 Feb 2021

Cited by 15 | Viewed by 6441

Abstract

Immunological memory is divided into many levels to counteract the provocations of diverse and ever-changing infections. Fast functions of effector memory and the superposition of both quantitatively and qualitatively plastic anticipatory memory responses together form the walls of protection against pathogens. Here we [...] Read more.

Immunological memory is divided into many levels to counteract the provocations of diverse and ever-changing infections. Fast functions of effector memory and the superposition of both quantitatively and qualitatively plastic anticipatory memory responses together form the walls of protection against pathogens. Here we provide an overview of the role of different B and T cell subsets and their interplay, the parallel and independent functions of the B1, marginal zone B cells, T-independent- and T-dependent B cell responses, as well as functions of central and effector memory T cells, tissue-resident and follicular helper T cells in the memory responses. Age-related limitations in the immunological memory of these cell types in neonates and the elderly are also discussed. We review how certain aspects of immunological memory and the interactions of components can affect the efficacy of vaccines, in order to link our knowledge of immunological memory with the practical application of vaccination. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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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 14 | Viewed by 5257

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

(This article belongs to the Collection COVID-19 Vaccines and Vaccination)

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10 pages, 267 KiB

Open AccessArticle

Vaccine Hesitancy among Italian Patients Recovered from COVID-19 Infection towards Influenza and Sars-Cov-2 Vaccination

by Valentina Gerussi, Maddalena Peghin, Alvisa Palese, Valentina Bressan, Erica Visintini, Giulia Bontempo, Elena Graziano, Maria De Martino, Miriam Isola and Carlo Tascini

Vaccines 2021, 9(2), 172; https://doi.org/10.3390/vaccines9020172 - 18 Feb 2021

Cited by 73 | Viewed by 5460

Abstract

We aimed to assess the attitude towards influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations among coronavirus disease 2019 (COVID-19) recovered patients. We performed a cross-sectional study consisting of a standardized telephone interview carried out between September and November 2020 targeting [...] Read more.

We aimed to assess the attitude towards influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations among coronavirus disease 2019 (COVID-19) recovered patients. We performed a cross-sectional study consisting of a standardized telephone interview carried out between September and November 2020 targeting a cohort of adult in- and out-patients that had recovered from COVID-19 after the first wave (March–May 2020) at Udine Hospital (Italy). Overall, 599 people participated (320 female, median age 53 years) and most had experienced an acute COVID-19 with mild illness (409, 68.3%). The majority were hesitant or undecided towards influenza (327, 54.6%) and SARS-CoV-2 (353, 59.2%) vaccines. Older age, public work exposure, and previous 2019 flu shots were the main factors associated with a positive attitude toward both vaccinations (p < 0.05). Being hospitalized during the acute COVID-19 phase was associated with the willingness to get a flu shot (94/272, 34.5%) but not SARS-CoV-2 vaccine (70/244, 28.7%). Vaccine hesitancy is diffuse and multifactorial also among COVID-19 recovered. Full article

(This article belongs to the Section Human Vaccines and Public Health)

24 pages, 1622 KiB

Open AccessReview

COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

by Muhammad Umer Ashraf, Yeji Kim, Sunil Kumar, Dongyeob Seo, Maryam Ashraf and Yong-Soo Bae

Vaccines 2021, 9(2), 171; https://doi.org/10.3390/vaccines9020171 - 18 Feb 2021

Cited by 48 | Viewed by 10075

Abstract

There are several emerging strategies for the vaccination of COVID-19 (SARS-CoV-2) however, only a few have yet shown promising effects. Thus, choosing the right pathway and the best prophylactic options in preventing COVID-19 is still challenging at best. Approximately, more than two-hundred vaccines [...] Read more.

There are several emerging strategies for the vaccination of COVID-19 (SARS-CoV-2) however, only a few have yet shown promising effects. Thus, choosing the right pathway and the best prophylactic options in preventing COVID-19 is still challenging at best. Approximately, more than two-hundred vaccines are being tested in different countries, and more than fifty clinical trials are currently undergoing. In this review, we have summarized the immune-based strategies for the development of COVID-19 vaccines and the different vaccine candidate platforms that are in clinical stages of evaluation, and up to the recently licensed mRNA-based COVID-19 vaccines of Pfizer-BioNtech and Moderna’s. Lastly, we have briefly included the potentials of using the ‘RPS-CTP vector system’ for the development of a safe and effective oral mucosal COVID-19 vaccine as another vaccine platform. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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9 pages, 1263 KiB

Open AccessArticle

Spain’s Hesitation at the Gates of a COVID-19 Vaccine

by Hans Eguia, Franco Vinciarelli, Marina Bosque-Prous, Troels Kristensen and Francesc Saigí-Rubió

Vaccines 2021, 9(2), 170; https://doi.org/10.3390/vaccines9020170 - 18 Feb 2021

Cited by 46 | Viewed by 9357

Abstract

(1) Background: This study aims to delineate a pattern on vaccine hesitancy in a sample of the Spanish population, considering age groups and status as healthcare workers. (2) Methods: Participants were recruited using Twitter^® as a dissemination tool to reach as many [...] Read more.

(1) Background: This study aims to delineate a pattern on vaccine hesitancy in a sample of the Spanish population, considering age groups and status as healthcare workers. (2) Methods: Participants were recruited using Twitter^® as a dissemination tool to reach as many respondents as possible in different parts of the Spanish territory. The participants were recruited in a cross-sectional study, which included answering an online questionnaire. Data were collected from 10 September through 23 November 2020. Respondents answered questions asking whether they intended to be vaccinated and provided the main reason for their answers. To estimate associations between vaccination hesitancy and independent variables, we fit Poisson regression models with robust variance. (3) Results: One thousand and two responses were obtained, of which only 731 were validated. One hundred and sixty-four participants stated that they would not be vaccinated (22.43%), of which 20–24% were non-health workers or unemployed, 17.5% physicians, 31.5% other health workers, and almost 35% nurses. Concerns about lack of effectiveness of the vaccination, lack of safety when vaccinating and possibly dangerous adverse effects were the main causes provided. (4) Conclusions: This study indicates that more interventions are needed to achieve better communication with the population and health professionals. Receptiveness to the message of the importance and security of the COVID-19 vaccination could be an important strategy for improving these results. Full article

(This article belongs to the Section Human Vaccines and Public Health)

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13 pages, 384 KiB

Open AccessArticle

Understanding the Influence of Individual and Systemic Factors on Vaccination Take-Up in European Citizens Aged 55 or Older

by Olympia E. Anastasiou and Dörte Heger

Vaccines 2021, 9(2), 169; https://doi.org/10.3390/vaccines9020169 - 17 Feb 2021

Cited by 9 | Viewed by 2722

Abstract

Background: High vaccination coverage provides extensive public health benefits. Hence, increasing vaccination rates is an important policy goal within the EU and worldwide. We aim to evaluate individual and systemic parameters associated with vaccination in European Union citizens aged 55 or older, using [...] Read more.

Background: High vaccination coverage provides extensive public health benefits. Hence, increasing vaccination rates is an important policy goal within the EU and worldwide. We aim to evaluate individual and systemic parameters associated with vaccination in European Union citizens aged 55 or older, using data from the Special Eurobarometer 488. Methods: Linear probability and probit models are estimated to analyze the determinants of vaccination take-up. Further, descriptive analyses are used to explore how the reasons for not having a vaccination differ by welfare regime. Results: High knowledge about the effectiveness and safety of vaccination increases the probability of receiving a vaccination during the past five years by 26 percentage points (pp), medium knowledge increases it by 15 pp. Focusing on the specific case of the flu, official recommendations increase this probability by, on average, 6 pp; while having to pay out-of-pocket for a recommended vaccination decreases it by, on average, 10 pp. Furthermore, the differences for no vaccination differ widely across welfare systems and television is the primary source for information about vaccination. Conclusions: Reported vaccination rates in Europe fall far below targets set by official recommendations. Increasing vaccination knowledge and offering vaccinations free of charge can help to increase vaccination rates. A specific focus should be put on reaching individuals with potential difficulties of access such as those living alone and unemployed. Full article

(This article belongs to the Special Issue Strategies to Increase Vaccination Coverage and Vaccine Confidence)

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11 pages, 1521 KiB

Open AccessArticle

Vaccination Status of Mothers and Children from the ‘Mamma & Bambino’ Cohort

by Martina Barchitta, Andrea Maugeri, Roberta Magnano San Lio, Maria Clara La Rosa, Claudia La Mastra, Giuliana Favara, Giuliana Giunta, Antonio Cianci and Antonella Agodi

Vaccines 2021, 9(2), 168; https://doi.org/10.3390/vaccines9020168 - 17 Feb 2021

Cited by 10 | Viewed by 2989

Abstract

According to the evidence demonstrating vaccines’ safety and effectiveness in anticipation of and during pregnancy, several countries have established immunization programs during the periconceptional period. Here, we evaluated vaccination status among 220 mother–child pairs, using data from the ‘Mamma & Bambino’ cohort. The [...] Read more.

According to the evidence demonstrating vaccines’ safety and effectiveness in anticipation of and during pregnancy, several countries have established immunization programs during the periconceptional period. Here, we evaluated vaccination status among 220 mother–child pairs, using data from the ‘Mamma & Bambino’ cohort. The self-reported data were evaluated at delivery, and with planned follow-ups at 1–2 years after delivery. In general, we noted that the vaccination status among the women was heterogeneous, ranging from 8.3% (vaccine against Human Papillomavirus, HPV) to 65.6% (vaccine against Diphtheria Tetanus and Pertussis, DTaP). Excluding the women who contracted the diseases in the past, the main ground for refusal was the lack of information. We also demonstrated that increasing age was associated with higher odds of not being vaccinated against Measles-Mumps-Rubella (MMR; OR = 1.12; 95% CI = 1.04–1.21; p = 0.004), HPV (OR = 1.20; 95% CI = 1.08–1.33; p = 0.001) and DTaP (OR =1.09; 95% CI = 1.01–1.18; p = 0.040). As expected, we showed that the proportion of newborns vaccinated with the Hexavalent and Pneumococcal vaccines was high (99.5% and 98.6%, respectively), while the vaccination coverage against MMRV did not reach the auspicated threshold (84.1%). Overall, these results underlined the need for the improvement of women’s knowledge about the recommendations for vaccination, especially during pregnancy. Full article

(This article belongs to the Special Issue Measles-Mumps-Rubella-Varicella Vaccination)

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11 pages, 1624 KiB

Open AccessArticle

Porvac^® Subunit Vaccine E2-CD154 Induces Remarkable Rapid Protection against Classical Swine Fever Virus

by Yusmel Sordo-Puga, Marisela Suárez-Pedroso, Paula Naranjo-Valdéz, Danny Pérez-Pérez, Elaine Santana-Rodríguez, Talia Sardinas-Gonzalez, Mary Karla Mendez-Orta, Carlos A. Duarte-Cano, Mario Pablo Estrada-Garcia and María Pilar Rodríguez-Moltó

Vaccines 2021, 9(2), 167; https://doi.org/10.3390/vaccines9020167 - 17 Feb 2021

Cited by 12 | Viewed by 4223

Abstract

Live attenuated C-strain classical swine fever vaccines provide early onset protection. These vaccines confer effective protection against the disease at 5–7 days post-vaccination. It was previously reported that intramuscular administration of the Porvac^® vaccine protects against highly virulent classical swine fever virus [...] Read more.

Live attenuated C-strain classical swine fever vaccines provide early onset protection. These vaccines confer effective protection against the disease at 5–7 days post-vaccination. It was previously reported that intramuscular administration of the Porvac^® vaccine protects against highly virulent classical swine fever virus (CSFV) “Margarita” strain as early as seven days post-vaccination. In order to identify how rapidly protection against CSFV is conferred after a single dose of the Porvac^® subunit vaccine E2-CD154, 15 swine, vaccinated with a single dose of Porvac^®, were challenged intranasally at five, three, and one day post-vaccination with 2 × 10³ LD₅₀ of the highly pathogenic Cuban “Margarita” strain of the classical swine fever virus. Another five animals were the negative control of the experiment. The results provided clinical and virological data confirming protection at five days post-vaccination. Classical swine fever (CSF)-specific IFNγ T cell responses were detected in vaccinated animals but not detected in unvaccinated control animals. These results provided the first data that a subunit protein vaccine demonstrates clinical and viral protection at five days post-vaccination, as modified live vaccines. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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11 pages, 1134 KiB

Open AccessCommunication

Immunogenicity of Calvenza-03 EIV/EHV^® Vaccine in Horses: Comparative In Vivo Study

by Selvaraj Pavulraj, Tobias Bergmann, Claudia Maria Trombetta, Serena Marchi, Emanuele Montomoli, Sidi Sefiane El Alami, Roberto Ragni-Alunni, Nikolaus Osterrieder and Walid Azab

Vaccines 2021, 9(2), 166; https://doi.org/10.3390/vaccines9020166 - 17 Feb 2021

Cited by 7 | Viewed by 3358

Abstract

Equine influenza (EI) is a highly contagious acute respiratory disease of equines that is caused mainly by the H3N8 subtype of influenza A virus. Vaccinating horses against EI is the most effective strategy to prevent the infection. The current study aimed to compare [...] Read more.

Equine influenza (EI) is a highly contagious acute respiratory disease of equines that is caused mainly by the H3N8 subtype of influenza A virus. Vaccinating horses against EI is the most effective strategy to prevent the infection. The current study aimed to compare the kinetics of EI-specific humoral- and cell-mediated immunity (CMI) in horses receiving either identical or mixed vaccinations. Two groups of horses were previously (six months prior) vaccinated with either Calvenza 03 EIV EHV^® (G1) or Fluvac Innovator^® (G2) vaccine. Subsequently, both groups received a booster single dose of Calvenza 03 EIV EHV^®. Immune responses were assessed after 10 weeks using single radial hemolysis (SRH), virus neutralization (VN), and EliSpot assays. Our results revealed that Calvenza-03 EIV/EHV^®-immunized horses had significantly higher protective EI-specific SRH antibodies and VN antibodies. Booster immunization with Calvenza-03 EIV/EHV^® vaccine significantly stimulated cell-mediated immune response as evidenced by significant increase in interferon-γ-secreting peripheral blood mononuclear cells. In conclusion, Calvenza-03 EIV/EHV^® vaccine can be safely and effectively used for booster immunization to elicit optimal long persisting humoral and CMI responses even if the horses were previously immunized with a heterogeneous vaccine. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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Vaccination and sampling regimen. Full article ">Figure 2
Mean EIV-specific antibody relative concentration determined by single radial hemolysis (SRH) assay. Serum samples were collected from groups 1 (G1) and 2 (G2) after six months of immunization (V1—day 0) with either Calvenza-03 EIV/EHV® (Group 1; G1: black circles) or Fluvac Innovator® (Group 2; G2: black squares) and after 10 weeks (V2—10 weeks) of booster immunization with Calvenza-03 EIV/EHV® for horses of both groups (G1: upright black triangles; G2: downright black triangles). SRH assay was performed as described in the materials and methods. Total area of hemolysis was measured in mm2. The central line in the scattered dot plot indicates the mean of the data with standard error of mean (error bars). ** A significant increase (2-way repeated measures ANOVA with Tukey’s multiple comparisons post-test; p < 0.01) of hemolysis area for group 1 was seen when compared to group 2. NS—not significant; vacci.—vaccination. Full article ">Figure 3
Mean EIV-specific serum neutralizing antibody titers determined by virus neutralization (VN) assay. Serum samples were collected from groups 1 (G1) and 2 (G2) after 6 months of immunization (V1—day 0) with either Calvenza-03 EIV/EHV® (group 1; G1: black circles) or Fluvac Innovator® (group 2; G2: black squares) and after 10 weeks (V2—10 weeks) of booster immunization with Calvenza-03 EIV/EHV® for horses of both groups (G1: upright black triangles; G2: downright black triangles), and VN assay was performed. The central line in the scattered dot plot indicates the mean of the data with standard error of mean (error bars). * A significant increase (2-way repeated measures ANOVA with Tukey’s multiple comparisons post-test; p < 0.05) of antibody titer for group 1 was seen when compared to group 2. NS—not significant; vacci.—vaccination. Full article ">Figure 4
ELISpot analysis for interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) from immunized horses. PBMC were collected from G1 and G2 horses before (day 0 = V1; G1: black circles; G2: upright black triangles) and after (10 weeks = V2; G1: black squares; G2: downright black triangle)) booster immunization. PBMC were isolated and stimulated with EIV. The response is presented as IFN-γ positive spot-forming cells per 106 PBMC. The central line in the scattered dot plot indicates the mean of the data with standard error of mean (error bars). * p < 0.05; ** p < 0.01 using 2-way repeated measures ANOVA with Tukey’s multiple comparisons post-test. Full article ">

22 pages, 1850 KiB

Open AccessArticle

A GMMA-CPS-Based Vaccine for Non-Typhoidal Salmonella

by Akosiererem S. Sokaribo, Sumudu R. Perera, Zoe Sereggela, Ryan Krochak, Lindsay R. Balezantis, Xiaohui Xing, Shirley Lam, William Deck, Sam Attah-Poku, Dennis Wade Abbott, Shantanu Tamuly and Aaron P. White

Vaccines 2021, 9(2), 165; https://doi.org/10.3390/vaccines9020165 - 17 Feb 2021

Cited by 7 | Viewed by 3716

Abstract

Non-typhoidal Salmonella are a major cause of gastroenteritis worldwide, as well as causing bloodstream infections in sub-Saharan Africa with a high fatality rate. No vaccine is currently available for human use. Current vaccine development strategies are focused on capsular polysaccharides (CPS) present on [...] Read more.

Non-typhoidal Salmonella are a major cause of gastroenteritis worldwide, as well as causing bloodstream infections in sub-Saharan Africa with a high fatality rate. No vaccine is currently available for human use. Current vaccine development strategies are focused on capsular polysaccharides (CPS) present on the surface of non-typhoidal Salmonella. This study aimed to boost the amount of CPS purified from S. Typhimurium for immunization trials. Random mutagenesis with Tn10 transposon increased the production of CPS colanic acid, by 10-fold compared to wildtype. Immunization with colanic acid or colanic acid conjugated to truncated glycoprotein D or inactivated diphtheria toxin did not induce a protective immune response in mice. However, immunization with Generalized Modules for Membrane Antigens (GMMAs) isolated from colanic acid overproducing isolates reduced Salmonella colonization in mice. Our results support the development of a GMMA-CPS-based vaccine against non-typhoidal Salmonella. Full article

(This article belongs to the Special Issue Vaccines and Other Antibody Therapies Against Bacterial Infection)

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Evaluating the role of yih operon in the virulence of S. Typhimurium. A competitive index experiment was performed with C57BL/6 mice orally infected with wildtype and S. Typhimurium 14028 Δyih. At 4–7 days post-infection, the CFU levels were enumerated from the liver, spleen, cecum and MLN. Each dot represents the CFU counts (per organ) from the designated organ from a single mouse. Competitive index values were calculated from each organ as follows: (CFU yih mutant/ wt)output/(CFU yih/wt)input. A CI value of 1, which represents a situation where both strains are equally virulent, is represented by the horizontal dotted line. Red circles represent CI values where the S. Typhimurium 14028 Δyih strain won the competition. Statistical differences between groups of mice were noted as ns: p > 0.05. Full article ">Figure 2
Expression of yihUTSRQPO and yihVW operons in S. Typhimurium. Promoter luciferase fusions for (A) yihUTSRQPO and (B) yihVW were used to measure expression in S. Typhimurium (ST, wildtype), S. Typhimurium ΔbcsA (ΔbcsA), S. Typhimurium ΔbcsA pBR322-yihVW (pyihVW), S. Typhimurium ΔbcsA ΔyihVW (ΔyihVW), S. Typhimurium ΔbcsA ΔyihW (ΔyihW) and S. Typhimurium ΔbcsA ΔyihW Tn10 (Tn10C). Cultures were grown in 1% tryptone at 28 °C with agitation, and luminescence (in counts per second (cps)) was recorded every 30 min for 48 hours. The log maximum CPS value recorded over 48 hours is shown. Statistical differences were noted as **** p < 0.0001, ns: p > 0.05. Full article ">Figure 3
Effect of different precursor sugars on the expression of yihUTSRQPO. The S. Typhimurium ΔbcsA (A) and S. Typhimurium ΔbcsA ΔyihW (B) strains were grown in 1% tryptone media supplemented with or without different precursor sugars (glucose, galactose, rhamnose, mannose, or all four sugars), at 28 °C. Luminescence (in counts per second (cps)) was recorded every 30 min for 48 hours. The log maximum CPS value recorded over 48 hours is shown. Statistical differences were noted as ** p < 0.01, *** p < 0.001, or ns: p > 0.05. Full article ">Figure 4
Immune response to colanic acid, truncated glycoprotein D and inactivated diphtheria toxin. ELISA was performed with serum collected from CB7BL/6 mice (A,C) or BALB/c mice (B,D), immunized with phosphate-buffered saline (PBS), colanic acid (CA), CA conjugated to inactivated diphtheria toxin (CA-CRM197) or CA conjugated to truncated glycoprotein D (CA-tgD). Full article ">Figure 5
Amounts of S. Typhimurium recovered from mice previously immunized with colanic acid. (A) C57BL/6 mice were immunized with phosphate buffered saline (PBS), colanic acid (CA) or CA conjugated to inactivated diphtheria toxin (CA-CRM197). (B) BALB/c mice were immunized with PBS, CA or CA conjugated to truncated glycoprotein D (CA-tgD). All immunized mice were orally challenged with 107 CFU of Salmonella, and 4–7 days post-infection, the liver, spleen, cecum, mesenteric lymph node (MLN) and blood (C57BL/6) were harvested. Organs were homogenized before plating on LB agar supplemented with kanamycin. The log10 CFU values of Salmonella recovered from individual organs from each mouse are shown. The dashed line represents the limit of detection of 100 CFU. For each group of mice, the black line represents the median values. Statistical significance: Not significant (ns): p > 0.05. Full article ">Figure 6
Immune response to GMMAs and colanic acid in immunized mice. Mice were immunized with GMMAs purified from S. Typhimurium 14028 ∆tolR (wildtype), S. Typhimurium 14028 ∆tolR ∆lon (Lon), Tn10C ∆tolR (Tn10C) or PBS. ELISA was performed with sera collected on days 0, 21, 42 and 63 and used to detect Anti-CPS IgG (A), Anti- ST GMMAs IgG (wildtype) (B), Anti-Lon GMMAs IgG (C) and Anti-Tn10C GMMAs IgG (D). Each point represents the value from an individual mouse, the horizontal line represents the median from each group of mice. Statistical significance: ns: p > 0.05. Full article ">Figure 7
Ability of GMMAs to protect mice against lethal challenge of S. Typhimurium. C57BL/6 mice were immunized with PBS and GMMAs purified from S. Typhimurium ΔtolR (wildtype), S. Typhimurium ΔtolR Δlon (Lon) and S. Typhimurium ΔtolR ΔbcsA ΔyihW Tn10dtet (Tn10C). Immunized mice were orally challenged with 107 CFU of S. Typhimurium 14028, and 4–7 days post-infection, mice were euthanized, and liver, spleen, cecum, MLN and blood were collected for bacterial enumeration. The log10 CFU of Salmonella recovered from each mouse is shown. The dotted line represents the limit of detection of 100 CFU. The black line represents the median log CFU values determined from each group of mice. Full article ">

14 pages, 2892 KiB

Open AccessArticle

Proteomic Analysis of ISGylation in Immortalized Porcine Alveolar Macrophage Cell Lines Induced by Type I Interferon

by Chengbo Zhu, Jingrui Li, Chaonan Tian, Mengmeng Qin, Zhenni Wang, Bingjun Shi, Guanggang Qu, Chunyan Wu and Yuchen Nan

Vaccines 2021, 9(2), 164; https://doi.org/10.3390/vaccines9020164 - 17 Feb 2021

Cited by 8 | Viewed by 3138

Abstract

Interferon-stimulated gene product 15 (ISG15), a ubiquitin-like molecule, can be conjugated to protein substrates through a reversible process known as ISGylation. ISG15 and ISGylation are both strongly upregulated by type I interferons and play putative key roles in host innate immunity against viral [...] Read more.

Interferon-stimulated gene product 15 (ISG15), a ubiquitin-like molecule, can be conjugated to protein substrates through a reversible process known as ISGylation. ISG15 and ISGylation are both strongly upregulated by type I interferons and play putative key roles in host innate immunity against viral infection. However, the function of ISGylation and identities of ISGylation substrates are largely unknown. Here, a novel monoclonal antibody (Mab) that specifically recognizes porcine ISG15 (pISG15) was employed to capture ISG15-conjugated proteins from IFNs-stimulated porcine cell lysates. Next, Mab-captured conjugates were analyzed using proteomics-based tools to identify potential ISGylation protein targets in order to elucidate the roles of ISG15 and ISGylation in porcine cells. Subsequently, 190 putative ISGylation sites were detected within 98 identified ISGylation candidates; several candidates contained more than one ISGylation-modifiable lysine residue, including pISG15 itself. Motif enrichment analysis of confirmed ISGylation sites demonstrated a moderate bias towards certain sites with specific upstream amino acid residues. Meanwhile, results of Gene Ontology (GO)-based annotation and functional enrichment and protein-protein interaction (PPI) network analyses of porcine ISG15-conjugated substrate proteins indicated that these substrates were mainly associated with the host metabolism, especially nucleotide metabolic pathways that ultimately may participate in cellular antiviral defenses. Notably, several ISGs (MX1, IFIT1, OAS1, ISG15 and putative ISG15 E3 ligase Herc6) were also identified as putative ISGylation substrates within a regulatory loop involving ISGylation of ISGs themselves. Taken together, proteomics analysis of porcine ISGylation substrates revealed putative functional roles of ISG15 and novel host ISGylation targets that may ultimately be involved in cellular antiviral responses. Full article

(This article belongs to the Special Issue Host Immune Response to Infectious Diseases)

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28 pages, 1443 KiB

Open AccessArticle

Non-Lethal Sequential Individual Monitoring of Viremia in Relation to DNA Vaccination in Fish–Example Using a Salmon Alphavirus DNA Vaccine in Atlantic Salmon Salmo salar

by Catherine Collins, Katherine Lester, Jorge Del-Pozo and Bertrand Collet

Vaccines 2021, 9(2), 163; https://doi.org/10.3390/vaccines9020163 - 17 Feb 2021

Cited by 2 | Viewed by 3780

Abstract

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not [...] Read more.

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not useful. Additionally, in fish experimental studies on vaccine efficacy and immune response the norm is that several individuals are lethally sampled at sequential timepoints, and results are extrapolated to represent the kinetics of immune and disease parameters of an individual fish over the entire experimental infection period. In the present study we developed a new approach to vaccine testing for viremic viruses in fish by following the same individuals over the course of a DNA vaccination and experimental infection through repeated blood collection and analyses. Injectable DNA vaccines are particularly efficient against viral disease in fish. To date, two DNA vaccines have been authorised for use in fish farming, one in Canada against Infectious Haemorrhagic Necrotic virus and more recently one in Europe against Salmon Pancreatic Disease virus (SPDv) subtype 3. In the current study we engineered and used an experimental DNA vaccine against SPDv subtype 1. We measured viremia using a reporter cell line system and demonstrated that the viremia phase was completely extinguished following DNA vaccination. Differences in viremia infection kinetics between fish in the placebo group could be related to subsequent antibody levels in the individual fish, with higher antibody levels at terminal sampling in fish showing earlier viremia peaks. The results indicate that sequential non-lethal sampling can highlight associations between infection traits and immune responses measured at asynchronous timepoints and, can provide biological explanations for variation in data. Similar to results observed for the SPDv subtype 3 DNA vaccine, the SPDv subtype 1 DNA vaccine also induced an interferon type 1 response after vaccination and provided high protection against SPDv under laboratory conditions when fish were challenged at 7 weeks post-vaccination. Full article

(This article belongs to the Special Issue Vaccines for Aquaculture)

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19 pages, 744 KiB

Open AccessReview

Strategies for Enhancement of Live-Attenuated Salmonella-Based Carrier Vaccine Immunogenicity

by James E. Galen, Rezwanul Wahid and Amanda D. Buskirk

Vaccines 2021, 9(2), 162; https://doi.org/10.3390/vaccines9020162 - 17 Feb 2021

Cited by 11 | Viewed by 3444

Abstract

The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a [...] Read more.

The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrier vaccine. It was first tested using a live-attenuated Salmonella enterica serovar Typhi strain in clinical trials in 1984, with excellent humoral immune responses against the carrier strain but only modest responses elicited against the foreign antigen. Since then, clinical trials with additional Salmonella-based carrier vaccines have been conducted. As with the original trial, only modest foreign antigen-specific immunity was achieved in most cases, despite the incorporation of incremental improvements in antigen expression technologies and carrier design over the years. In this review, we will attempt to deconstruct carrier vaccine immunogenicity in humans by examining the basis of bacterial immunity in the human gastrointestinal tract and how the gut detects and responds to pathogens versus benign commensal organisms. Carrier vaccine design will then be explored to determine the feasibility of retaining as many characteristics of a pathogen as possible to elicit robust carrier and foreign antigen-specific immunity, while avoiding over-stimulation of unacceptably reactogenic inflammatory responses. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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25 pages, 1139 KiB

Open AccessArticle

Protection Elicited by Attenuated Live Yersinia pestis Vaccine Strains against Lethal Infection with Virulent Y. pestis

by Christopher K. Cote, Sergei S. Biryukov, Christopher P. Klimko, Jennifer L. Shoe, Melissa Hunter, Raysa Rosario-Acevedo, David P. Fetterer, Krishna L. Moody, Joshua R. Meyer, Nathaniel O. Rill, Jennifer L. Dankmeyer, Patricia L. Worsham, Joel A. Bozue and Susan L. Welkos

Vaccines 2021, 9(2), 161; https://doi.org/10.3390/vaccines9020161 - 16 Feb 2021

Cited by 16 | Viewed by 4499

Abstract

The etiologic agent of plague, Yersinia pestis, is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable [...] Read more.

The etiologic agent of plague, Yersinia pestis, is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable and potentially vulnerable to vaccine resistance. We evaluated the safety and efficacy of eight live Y. pestis strains derived from virulent strains CO92 or KIM6+ and mutated in one or more virulence-associated gene(s) or cured of plasmid pPst. Stringent, single-dose vaccination allowed down-selection of the two safest and most protective vaccine candidates, CO92 mutants pgm- pPst- and ΔyscN. Both completely protected BALB/c mice against subcutaneous and aerosol challenge with Y. pestis. Strain CD-1 outbred mice were more resistant to bubonic (but not pneumonic) plague than BALB/c mice, but the vaccines elicited partial protection of CD-1 mice against aerosol challenge, while providing full protection against subcutaneous challenge. A ΔyscN mutant of the nonencapsulated C12 strain was expected to display antigens previously concealed by the capsule. C12 ΔyscN elicited negligible titers to F1 but comparable antibody levels to whole killed bacteria, as did CO92 ΔyscN. Although one dose of C12 ΔyscN was not protective, vaccination with two doses of either CO92 ΔyscN, or a combination of the ΔyscN mutants of C12 and CO92, protected optimally against lethal bubonic or pneumonic plague. Protection against encapsulated Y. pestis required inclusion of F1 in the vaccine and was associated with high anti-F1 titers. Full article

(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)

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Splenocytes were harvested and re-stimulated for cytokine/chemokine expression with (A) F1-V fusion protein vaccine, (B) γ-radiation inactivated Y. pestis CO92, or (C) γ-radiation inactivated Y. pestis C12 (nonencapsulated) bacteria and the supernatants were evaluated for cytokine expression by Luminex (n = 5 for each group). The fold changes in cytokines/chemokines in splenocytes were determined by dividing the geometric mean of log-transformed data (pg/mL) of the cytokine/chemokine by that of the negative control (Kphos) within each group of vaccinated mice. Of note, the antigen used to stimulate the splenocytes resulted in differential cytokine expression profiles (e.g., IFN-γ was significantly upregulated by the addition of the F1-V immunogen but was not significantly upregulated by either killed whole cell antigen relative to naïve mice). Due to the less defined whole bacterial cell immunogens and their impacts on splenocytes harvested from naïve mice, the fold change data normalize the immune responses elicited by the F1-V recombinant protein compared to γ-irradiated Y. pestis cells. The Y-axis (fold change relative to Kphos) scale is different in each graph. Full article ">Figure 1 Cont.
Splenocytes were harvested and re-stimulated for cytokine/chemokine expression with (A) F1-V fusion protein vaccine, (B) γ-radiation inactivated Y. pestis CO92, or (C) γ-radiation inactivated Y. pestis C12 (nonencapsulated) bacteria and the supernatants were evaluated for cytokine expression by Luminex (n = 5 for each group). The fold changes in cytokines/chemokines in splenocytes were determined by dividing the geometric mean of log-transformed data (pg/mL) of the cytokine/chemokine by that of the negative control (Kphos) within each group of vaccinated mice. Of note, the antigen used to stimulate the splenocytes resulted in differential cytokine expression profiles (e.g., IFN-γ was significantly upregulated by the addition of the F1-V immunogen but was not significantly upregulated by either killed whole cell antigen relative to naïve mice). Due to the less defined whole bacterial cell immunogens and their impacts on splenocytes harvested from naïve mice, the fold change data normalize the immune responses elicited by the F1-V recombinant protein compared to γ-irradiated Y. pestis cells. The Y-axis (fold change relative to Kphos) scale is different in each graph. Full article ">

14 pages, 1470 KiB

Open AccessReview

COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates

by Malik Sallam

Vaccines 2021, 9(2), 160; https://doi.org/10.3390/vaccines9020160 - 16 Feb 2021

Cited by 1412 | Viewed by 117116

Abstract

Utility of vaccine campaigns to control coronavirus 2019 disease (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and healthcare workers appears to have a decisive role in the successful control of the pandemic. The aim [...] Read more.

Utility of vaccine campaigns to control coronavirus 2019 disease (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and healthcare workers appears to have a decisive role in the successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on 25 December 2020. Results from 31 peer-reviewed published studies met the inclusion criteria and formed the basis for the final COVID-19 vaccine acceptance estimates. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). However, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors and nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In the majority of survey studies among the general public stratified per country (29/47, 62%), the acceptance of COVID-19 vaccination showed a level of ≥70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East and North Africa, Sub-Saharan Africa, Eastern Europe, Central Asia, Middle and South America. Addressing the scope of COVID-19 vaccine hesitancy in various countries is recommended as an initial step for building trust in COVID-19 vaccination efforts. Full article

(This article belongs to the Special Issue Vaccine Hesitancy and Child Immunizations: Rationales, Issues and Knowledge Gaps)

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15 pages, 2137 KiB

Open AccessArticle

A Novel Effective and Safe Vaccine for Prevention of Marek’s Disease Caused by Infection with a Very Virulent Plus (vv+) Marek’s Disease Virus

by Yifei Liao, Sanjay M. Reddy, Owais A. Khan, Aijun Sun and Blanca Lupiani

Vaccines 2021, 9(2), 159; https://doi.org/10.3390/vaccines9020159 - 16 Feb 2021

Cited by 12 | Viewed by 4124

Abstract

Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset lymphoma in chickens. Marek’s disease (MD) is effectively controlled using vaccination; however, MDV continues to break through vaccinal immunity, due to the emergence of highly virulent field strains. Earlier studies [...] Read more.

Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset lymphoma in chickens. Marek’s disease (MD) is effectively controlled using vaccination; however, MDV continues to break through vaccinal immunity, due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV resulted in an attenuated virus that protects against MD in chickens challenged with highly virulent field strains. However, the meq deleted virus retains the ability to induce significant lymphoid organ atrophy. In a different study, we found that the deletion of the vIL8 gene resulted in the loss of lymphoid organ atrophy in inoculated chickens. Here, we describe the generation of a recombinant MDV from which both meq and vIL8 genes were deleted. In vitro studies revealed that the meq and vIL8 double deletion virus replicated at levels similar to the parental very virulent plus (vv+) virus. In addition, in vivo studies showed that the double deletion mutant virus (686BAC-ΔMeqΔvIL8) conferred protection comparable to CVI988, a commercial vaccine strain, when challenged with a vv+ MDV virus, and significantly reduced lymphoid organ atrophy, when compared to meq null virus, in chickens. In conclusion, our study describes the development of a safe and effective vaccine candidate for prevention of MD in chickens. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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Figure 1
In vitro characterization of meq and vIL8 single and double deletion mutant viruses. (A) Genomic structure of serotype 1 Marek’s disease virus (MDV) and location of meq and vIL8 genes. UL: unique long; US: unique short; TRL and IRL: terminal and internal repeat long; TRS and IRS: terminal and internal repeat short. (B) Genomic analysis of meq and/or vIL8 deletion viruses. DNA of 686BAC (lanes 1 and 5), 686BAC-ΔMeq (lanes 2 and 6), 686BAC-ΔvIL8 (lanes 3 and 7) and 686BAC-ΔMeqΔvIL8 (lanes 4 and 8) were digested with BamHI or EcoRI, followed by agarose gel electrophoresis. Asterisks indicate different bands due to deletion of the meq and/or vIL8 genes. M: 1 kb plus ladder. (C) PCR analysis of viral genome isolated from infected chicken embryonic fibroblasts (CEF), using primers specific for MDV ribonucleotide reductase (RR), and meq and vIL8 flanking primers. Lane 1: 686 virus; lane 2: 686BAC virus; lane 3: 686BAC-ΔMeq virus; lane 4: 686BAC-ΔvIL8 virus; lane 5: 686BAC-ΔMeqΔvIL8 virus. (D) Immunofluorescence assay (IFA). 686BAC, 686BAC-ΔMeq, 686BAC-ΔvIL8 or 686BAC-∆Meq∆vIL8 BAC transfected CEF were subjected to IFA using MDV pp38 specific monoclonal antibody and FITC conjugated secondary antibody. Scale bar = 100 µm. (E) In vitro growth kinetics. CEF were infected with 100 plaque-forming units (PFU) of 686BAC, 686BAC-ΔMeq, 686BAC-ΔvIL8 and 686BAC-ΔMeqΔvIL8 viruses. Infected cells were trypsinized, diluted, and co-seeded with fresh CEF at the indicated time points, and plaques were counted 6 days post infection. Each point represents two independent experiments and data present average plaque numbers ± standard error of the mean (SEM). Full article ">Figure 2
In vivo replication and reactivation of meq and vIL8 single and double deletion mutant viruses. (A) Virus genome copy number in spleen of inoculated chickens. Genomic DNA were extracted from splenocytes of inoculated chickens at 5, 14, and 56 days post-inoculation (dpi) and virus genome copy number was measured by qPCR. 686BAC and 686BAC-ΔvIL8 viruses inoculated chickens were not tested (NT) at day 56, as all the chickens in those groups had died. Results are presented as average MDV genome copies per GAPDH copy of three chickens, and error bars represent standard error of the mean (SEM). (B) Virus reactivation assay. CEF were co-seeded with 106 peripheral blood lymphocytes (PBL) isolated from 686BAC, 686BAC-ΔMeq, 686BAC-ΔvIL8, or 686BAC-ΔMeqΔvIL8 virus inoculated chickens at 14 dpi. Plaques were counted 7 days after infection. Data present average plaque numbers of three chickens ± SEM. Full article ">Figure 3
Replication of meq and vIL8 double deletion virus in lymphoid organs and feather follicle epithelium (FFE) of inoculated chickens. At 5 or 14 days post-inoculation (dpi), lymphoid organs (spleen, thymus, and bursa) and feather follicle epithelium (FFE) were collected, respectively, from chickens inoculated with 686BAC or 686BAC-∆Meq∆vIL8 viruses, or negative control chickens. Tissue samples were frozen immediately using the O.C.T. (optimal cutting temperature) compound and 6 to 8 µm-thick cryostat sections were stained with MDV pp38 specific monoclonal antibody. Scale bar = 50 µm. Full article ">Figure 4
Pathogenesis studies of meq and vIL8 single and double deletion mutant viruses. One-day-old SPF MDV Ab– chickens were inoculated with 2000 plaque-forming units (PFU) of 686BAC, 686BAC-ΔMeq, 686BAC-ΔIL8 or 686BAC-ΔMeqΔIL8 viruses, or kept uninoculated and served as negative control. Chickens were maintained in isolation for 65 days and daily mortality was recorded. (A) Lymphoid organ atrophy. At 14 days post-inoculation (dpi), five chickens from each group were euthanized, the lymphoid organs collected, and the relative bursa and thymus to body weight was determined. Results represent mean value with error bars representing standard error of the mean. **: p < 0.01. (B) Survival curves of chickens inoculated with the indicated viruses or uninoculated control group. Full article ">Figure 5
Protection studies of meq and vIL8 double deletion virus in MDV maternal antibodies negative (Ab–) and positive (Ab+) chickens. Fifteen one-day-old SPF MDV Ab– (A) and commercial MDV Ab+ (B) chickens were unvaccinated or vaccinated with 2000 plaque-forming units (PFU) of 686BAC-∆Meq, 686BAC-∆Meq∆vIL8, or CVI988/Rispens subcutaneously. Five days later, vaccinated and unvaccinated control chickens were challenged subcutaneously with 500 PFU of MDV 686 strain virus. Survival curves of each group are presented. The trends of chicken survival over time were examined with LogRank and Wilcoxon tests. ns: no significant difference to CVI988/Rispens vaccinated group. Full article ">

3 pages, 181 KiB

Open AccessEditorial

Vaccine Development for Herpes Simplex Viruses: A Commentary of Special Issue Editors

by Antonella Caputo and Peggy Marconi

Vaccines 2021, 9(2), 158; https://doi.org/10.3390/vaccines9020158 - 16 Feb 2021

Cited by 2 | Viewed by 2660

Abstract

Herpes simplex virus type 1 and 2 (HSV1 and HSV2) are global, widespread human pathogens transmitted by direct contact that cause lifelong, recurrent asymptomatic and painful symptomatic clinical illnesses (cold sores, keratitis, blepharitis, meningitis, encephalitis, genital infections), overt disease and severe sequelae in [...] Read more.

Herpes simplex virus type 1 and 2 (HSV1 and HSV2) are global, widespread human pathogens transmitted by direct contact that cause lifelong, recurrent asymptomatic and painful symptomatic clinical illnesses (cold sores, keratitis, blepharitis, meningitis, encephalitis, genital infections), overt disease and severe sequelae in neonatal and immune-compromised patients, and increased risk of cervical cancer and other sexually transmitted infections, including HIV [...] Full article

(This article belongs to the Special Issue Vaccine Development for Herpes Simplex Viruses)

14 pages, 1163 KiB

Open AccessArticle

A Bacterially-Expressed Recombinant Envelope Protein from Usutu Virus Induces Neutralizing Antibodies in Rabbits

by Kinga Böszörményi, Janet Hirsch, Gwendoline Kiemenyi Kayere, Zahra Fagrouch, Nicole Heijmans, Roberto Rodriguez Garcia, Soesjiel Dwarka, Amy van Dijke, Boyd Aaldijk, Ronald Limpens, Montserrat Barcena, Bram Koster, Babs Verstrepen, Willy Bogers, Clemens Kocken, Gesine Cornellissen, Ernst Verschoor and Bart Faber

Vaccines 2021, 9(2), 157; https://doi.org/10.3390/vaccines9020157 - 16 Feb 2021

Cited by 5 | Viewed by 3081

Abstract

Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of [...] Read more.

Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of other flaviviruses, like West Nile virus and Zika virus, and will spread via its mosquito vectors and bird hosts to other parts of the world. Several cases of human infections by Usutu virus have already been published. Anticipating this spread, development of an efficacious vaccine would be highly desirable. Method: This study describes the production in E. coli, purification, and refolding of a partial USUV envelope protein. Prior to immunization, the protein was characterized using size exclusion chromatography, transmission electron microscopy and dynamic light scattering, showing the limited presence of virus-like structures, indicating that the protein solution is probably a mixture of mono and multimeric envelope proteins. Results: Immunizations of two rabbits with the refolded E-protein fraction, mixed with a strong adjuvant, resulted in the generation of neutralizing antibodies, as evidenced in an in vitro assay. Discussion: The way forward towards a subunit vaccine against Usutu virus infection is discussed. Full article

(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)

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(A) Coomassie-stained SDS-PAGE gel showing the purification procedure of USUV E protein from E. coli, starting with isolated inclusion bodies. Lane 1, inclusion bodies solubilized in 20 mM Tris, 8.0 M urea, pH 8.0, prior to application on the Ni-IMAC column; lane 2, Flow-through; lane 3, wash with 20 mM Tris, 8.0 M urea pH 8.0, 10 mM imidazole; lane 4, elution with 20 mM Tris, 8.0 M urea pH 8.0, 100 mM imidazole. (B) Western blot analysis of the purified USUV E protein (as in lane 4 of panel A), developed using mouse anti-HIS as the primary antibody. Full article ">Figure 2
(A) Size-exclusion chromatography of USUV E protein fraction after a refolding procedure using rapid dilution (blue line), compared to a mixture of protein markers (grey line) with their molecular mass indicated. (B) SDS-PAGE analysis (non-reduced) of collected 1 mL fractions of the SE-chromatography. Lanes 1; fraction 16–18 min; lanes 2, 18–20 min; lanes 3, 20–22 min, lanes 4, 22–24 min, lanes 5, 24–26 min, and lanes 6, 26–28 min. (C) SDS-PAGE analysis (non-reduced) of collected 1 mL fractions of the SE-chromatography. Lanes are identical as described for Panel B. Full article ">Figure 3
Electron microscopic analysis of purified USUV E protein. Purified USUV E antigen was negatively-stained with PTA and examined under EM. The scale bar indicates a size of 200 nm. Full article ">Figure 4
Dynamic Light Scattering analysis of the USUV E protein fraction showing the intensity-weighed particle distribution profile. Full article ">Figure 5
ELISA of two rabbit sera obtained after immunization, including 2 control sera after immunization with a control protein purified using a highly similar procedure. Squares represent day 28 (final bleed) sera from USUV E protein immunized animals, open symbol is serum 710, closed is serum 711. Diamonds represents 2 sera of control protein immunized animals, for which the protein was purified in a highly similar fashion. Circles represent pre-bleed sera from rabbits 710 (open) and 711 (closed). Starting dilution was 1:150. Full article ">Figure 6
Dot blot of heat-inactivated supernatants of Vero cell-grown USUV strains, stained with pooled rabbit serum of USUV E protein-immunized rabbits. Upper row: USUV, European lineage 3 isolate; lower row, supernatants of USUV, African lineage 3. Supernatants were concentrated and spotted in a 1:3 dilution series. The spot to the right is a positive control, containing the immunogen (E.coli-produced USUV E protein). Full article ">

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Vaccines, Volume 9, Issue 2 (February 2021) – 120 articles

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