Search Results (350)

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of heritability on the proneness as well as infection- and vaccine-induced immune responses have been documented for multiple infections, including tuberculosis, malaria, leprosy, otitis media, polio, mumps, measles, rubella, influenza, hepatitis B, and human papillomavirus infections, and recently, SARS-CoV-2. The current data show the heritable aspect in nearly all infections considered. In this contribution, we review and discuss human twin studies on the heritability of host characteristics in liability and response to IDs. This review emphasizes the importance of considering factors such as sex, disease stages, and disease presentation when assessing heritability and argues that the classical twin design provides a unique circumstance for exploring the genetic contribution as twins share levels of maternal antibodies, ancestral background, often the dates and number of vaccine doses, differences in vaccines’ manufacturing and storage, age, family environment, and other exposures. Additionally, we highlight the value of twin studies and the usefulness of combining the twin model with contemporary genomics technologies and advanced statistical tools to grasp a comprehensive and nuanced understanding of heritability in IDs. Full article

Cytomegalovirus (CMV) infection during pregnancy poses significant maternal and fetal health risks. Valacyclovir, an antiviral drug, has been explored as a therapeutic option for managing primary CMV infections in pregnant women. This study investigates the effects of valacyclovir therapy on immune response maturation against CMV, maternal antibody levels, and viral replication during treatment. We conducted a retrospective observational study involving pregnant women diagnosed with primary CMV infection and presenting in utero infection who received high-dose valacyclovir therapy (8 g/day). A group started the therapy at diagnosis, while another group started only after positive amniocentesis. Maternal antibody levels (IgM, IgG, and IgG avidity) and PCR for CMV testing (in blood, urine, and saliva) were measured longitudinally during the second and third trimesters. Our findings indicate that early valacyclovir therapy is related to lower avidity levels over time and a delay in reaching a high IgG avidity level (18.22 ± 1.21 weeks) compared to the patients who started Valacyclovir during the second trimester after positive amniocentesis (14.52 ± 1.64 weeks; p = 0.066). The therapy does not condition the overall concentration of maternal CMV-specific IgM and IgG. While high-dose VCV does not directly target the mechanism of IgG avidity maturation, it can interfere with this process by reducing the viral load and antigen presentation, influencing IgG avidity maturation. Further research is needed to elucidate the long-term implications of potential immunological modulation induced by Valacyclovir and to optimize early diagnosis and the right treatment protocol during pregnancy. Full article

Background: Maternal-derived antibody (MDA) interferes with immune responses, leading to the failure of H9N2 avian influenza vaccinations in poultry. So far, none of the commercially available H9N2 avian influenza vaccines used in poultry have been able to overcome MDA interference. Methods: To develop a vaccine that can overcome MDA interference, one or multiple copies of the minimum-binding domain (P29) from the complement protein C3d were inserted in between the signal peptide and the head domain of the hemagglutinin (HA) protein on a H9N2 avian influenza virus (A/Chicken/Shanghai/H514/2017, named H514). Results: The HA proteins containing P29 stimulated stronger type I interferences than wild-type HA proteins in vitro. The modified viruses with the HA proteins containing one copy of P29 (rH514-P29.1) and two copies of P29.2 (rH514-P29.2) were successfully rescued using reverse genetics. The inactivated vaccines developed with rH514-P29.1 or rH514-P29.2 induced higher and faster humoral immune responses than the vaccine developed with rH514 in specific pathogen-free (SPF) chickens. To evaluate the vaccines’ efficacy in the presence of MDA and to ensure a uniform level of MDA, passively transferred antibody (PTA) was used as a model to mimic MDA in 1-day-old SPF chickens. Our results showed that the rH514-P29.2 inactivated vaccine induced significantly higher HI titers than the rH514 inactivated vaccine in the presence of PTA. More importantly, it reduced viral shedding after being challenged with H514 in the presence of PTA. Conclusions: Our results suggest that vaccine antigens fused with two copies of P29 can decrease the interference of MDA on immunity in chickens. Overall, our results provide a new strategy for overcoming MDA interference. Full article

Prepartum vaccinations against neonatal calf diarrhea pathogens are administered in late pregnancy to provide passive immunity to calves through protective colostral antibodies. Potential non-specific effects of the vaccine on maternal innate immune responses and disease susceptibility during the sensitive transition period have not been addressed so far. In this retrospective study, data from 73,378 dairy cows on 20 farms in Germany were analyzed, using linear mixed-effects regression, quantile regression, and decision-tree-algorithms, to investigate the effects of prepartum vaccination on mammary health and milk yield by comparing non-vaccinated and vaccinated transition periods. Herd management-related factors were found to be most influential for mammary health and milk yield. Vaccinated cows were not significantly more likely to develop mastitis and did not have significantly different somatic cell counts and milk yields compared to non-vaccinated cows. Healthy primiparous cows with and without vaccination had similar energy-corrected milk yields. The study concludes that prepartum vaccination against calf diarrhea has no significant effects on mammary health and milk yield. Further research is recommended to investigate potential non-specific vaccine effects on other organ systems, infectious diseases, and production metrics of the dairy cow. Full article

Poultry production systems are usually exposed to important infections that could be prevented by vaccination programs. Conventional methods of vaccination such as drinking water; spray, eye, or nose inoculation; and injection are usually given after hatching and have many disadvantages. Therefore, there is a great need for searching of alternative ways for vaccination process. In ovo vaccination technology is now regarded as an alternative approach to post-hatch vaccination in modern poultry operations. This technique is effective, fast, provides uniform vaccine dosing and delivery, is suitable for massive production, and reduces labor costs. Routine in ovo vaccination is applied during the late stage of embryonic development between days 17.5 and 19.25 of egg incubation. The best route of inoculation of the vaccine is in the amniotic fluid or in the embryo’s muscles, without causing any hatchability or chick quality losses. Accordingly, the inoculation site, the age of the embryos and breeders, presence of maternal antibodies, and the sanitation of equipment’s and the environment during the vaccination process affect the efficiency of the in ovo vaccination technique. In ovo vaccination technology is currently applied for vaccination against several economically important viral diseases such as Newcastle, infectious bursal disease, Marek’s disease, infectious laryngotracheitis, infectious bronchitis, avian influenza, and avian metapneumovirus. Moreover, vaccines used for prevention of mycoplasmosis and coccidiosis could be applied in ovo instead of in post-hatching application. It can be concluded that in ovo vaccination is a rapidly growing trend of vaccine technology, and it can replace post-hatching vaccination conventional methods. Full article

Background: West Nile Virus [WNV] is a mosquito-borne flavivirus. It has spread globally, causing asymptomatic to severe neurological diseases in humans, with an increased risk in older adults and those with underlying conditions. This review examines WNV’s impact on pregnancy, focusing on maternal and neonatal symptoms and risks. Methods: This systematic review included primary studies from “PUBMED” and “SCOPUS” databases, as well as Google and Google Scholar, conducted in July 2024 using the appropriate keywords. This review adhered to PRISMA guidelines and utilized the Newcastle–Ottawa scale for bias assessment. Results: Seven primary studies were included in the systematic review. Fever was the predominating symptom, including neurological manifestations, respiratory symptoms, myalgia, weakness, nausea, vomiting, and rashes. Delivery, in most cases, progressed without any complications, while no infection was noted. Most of the neonates had a normal Apgar score, and their developmental functions did not seem to be affected. Even though, antibodies against WNV were detected in breast milk, no association with transmission to the neonate was observed. Conclusions: WNV infection is mostly associated with favorable outcomes during pregnancy. However, larger cohorts are needed to confirm our conclusions. Prompt diagnosis and public health surveillance are pivotal to eliminate disease transmission. Full article

(1) Background: Fetal chromosomal examination is a critical component of modern prenatal testing. Traditionally, maternal serum biomarkers such as free β-human chorionic gonadotropin (Free β-HCG) and pregnancy-associated plasma protein A (PAPPA) have been employed for screening, achieving a detection rate of approximately 90% for fetuses with Down syndrome, albeit with a false positive rate of 5%. While amniocentesis remains the gold standard for the prenatal diagnosis of chromosomal abnormalities, including Down syndrome and Edwards syndrome, its invasive nature carries a significant risk of complications, such as infection, preterm labor, or miscarriage, occurring at a rate of 7 per 1000 procedures. Beyond Down syndrome and Edwards syndrome, other chromosomal abnormalities, such as trisomy of chromosomes 9, 16, or Barr bodies, pose additional diagnostic challenges. Non-invasive prenatal testing (NIPT) has emerged as a powerful alternative for fetal genetic screening by leveraging maternal blood sampling. However, due to the extremely low abundance of fetal cells in maternal circulation, NIPT based on fetal cells faces substantial technical challenges. (2) Methods: Fetal nucleated red blood cells (FnRBCs) were first identified in maternal circulation in a landmark study published in The Lancet in 1959. Due to their fetal origin and presence in maternal peripheral blood, FnRBCs represent an ideal target for non-invasive prenatal testing (NIPT). In this study, we introduce a novel self-assembled cell array (SACA) chip system, a microfluidic-based platform designed to efficiently settle and align cells into a monolayer at the chip’s base within five minutes using lateral flow dynamics and gravity. This system is integrated with a fully automated, multi-channel fluorescence scanning module, enabling the real-time imaging and molecular profiling of fetal cells through fluorescence-tagged antibodies. By employing a combination of Hoechst+/CD71+/HbF+/CD45− markers, the platform achieves the precise enrichment and isolation of FnRBCs at the single-cell level from maternal peripheral blood. (3) Results: The SACA chip system effectively reduces the displacement of non-target cells by 31.2%, achieving a single-cell capture accuracy of 97.85%. This isolation and enrichment system for single cells is well suited for subsequent genetic analysis. Furthermore, the platform achieves a high purity of isolated cells, overcoming the concentration detection limit of short tandem repeat (STR) analysis, demonstrating its capability for reliable non-invasive prenatal testing. (4) Conclusions: This study demonstrates that the SACA chip, combined with an automated image positioning system, can efficiently isolate single fetal nucleated red blood cells (FnRBCs) from 50 million PBMCs in 2 mL of maternal blood, completing STR analysis within 120 min. With higher purification efficiency compared to existing NIPT methods, this platform shows great promise for prenatal diagnostics and potential applications in other clinical fields. Full article

Background/Objective: Duck virus hepatitis (DVH), caused by duck hepatitis A virus (DHAV), poses significant challenges to duck farming due to high mortality rates in young ducklings. Despite the widespread use of live attenuated vaccines, the genetic diversity within DHAV strains has diminished their cross-protection efficacy. This study aimed to evaluate the cross-protective efficacy of current DHAV-1 and DHAV-3 vaccines against genetically divergent wild strains. Methods: Phylogenetic analyses of the VP1 genes from DHAV-1 and DHAV-3 were conducted. Both DHAV-1 and DHAV-3 vaccines were tested in ducklings, with and without maternal-derived antibodies (MDA), through challenge trials with homologous and heterologous strains. Results: In the phylogenetic analysis, compared to vaccine strains, DHAV-1 and DHAV-3 field variant strains were classified into different genotypes. In ducklings without MDA, the DHAV-1 vaccine provided 60% survival against homologous strains by 2 days post-vaccination (DPV) and complete protection by 4 DPV, while survival rates against heterologous strains ranged from 40 to 60%. In ducklings with MDA, the DHAV-1 vaccine provided full protection with an additional vaccination for day-old ducklings against heterologous strains. The DHAV-3 vaccine conferred complete protection against both homologous and heterologous strains by 2 DPV, regardless of MDA presence. Conclusions: The DHAV-3 vaccine demonstrated robust cross-protection across genotypes, while the DHAV-1 vaccine showed limitations against genetically divergent strains. These findings highlight the necessity for genotype-matched vaccines and optimized immunization strategies to enhance protection against evolving DHAV field strains. Full article

Preeclampsia is a pregnancy-specific hypertensive syndrome recognized as the leading cause of maternal and fetal morbidity worldwide. Early diagnosis is crucial for mitigating its adverse effects, and recent investigations have identified endoglin as a potential biomarker for this purpose. Here, we present the development of a hybrid biosensor platform for the ultrasensitive detection of endoglin, aimed at enabling the early diagnosis of preeclampsia. This platform integrates the high surface area properties of nanoporous anodic alumina (NAA) with the unique optical characteristics of gold nanoclusters (AuNCs) to achieve enhanced detection capabilities. The NAA surface functionalized to promote attachment of AuNCs, which then was functionalized with specific antibodies to confer selectivity towards endoglin. Photoluminescence (PL) analysis of the biosensor demonstrated a linear detection range of 10–50 ng/mL, with a detection limit of 5.4 ng/mL and a sensitivity of 0.004 a.u./(ng/mL). This proof-of-concept study suggests that the NAA-AuNCs-based biosensing platform holds significant potential for the development of ultrasensitive, portable, and cost-effective diagnostic tools for preeclampsia, offering a promising avenue for advancing prenatal care. Full article

Two experiments assessed the effects of providing a vitamin and mineral supplement to gestating beef heifers on concentrations of immunoglobulins (Ig) in colostrum and calf serum 24 h after feeding maternal colostrum (Exp. 1) or a colostrum-replacement product (Exp. 2). Angus-based heifers (n = 31, Exp. 1; n = 14, Exp. 2) were fed a basal diet (CON) or were fed a basal diet plus a vitamin and mineral supplement (VTM) from breeding (Exp. 1) or 60 d pre-breeding (Exp. 2) through calving. Colostrum was collected at calving, and serum was collected from calves 24 h after colostrum consumption to evaluate passive transfer. Serum was collected from calves in Exp. 1 to determine serum titers in response to vaccination at birth, pasture turn out, weaning, and 14 d after vaccination. Concentrations of IgG, IgM, or IgA in colostrum or in calf serum at 24 h were not impacted by dam treatment (p ≥ 0.21); however, concentrations of Ig in calf serum at 24 h were greater (p ≤ 0.01) in calves receiving maternal colostrum than those receiving a colostrum replacer. Calves born to VTM heifers had greater antibody titers at birth, pasture turn out, and weaning for infectious bovine rhinotracheitis (IBR), bovine viral diarrhea virus type 2 (BVD-2), and bovine respiratory syncytial virus (BRSV), respectively. Our results suggest that the programming of immune function in calves via prenatal nutrition appears to extend postnatally in CON and VTM offspring. Full article

Background/Objectives: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants worldwide. Maternal immunization to protect younger infants is supported by evidence that virus-neutralizing antibodies, which are efficiently transferred across the placenta from mother to fetus, are a primary immune mediator of protection. In maternal RSV vaccine studies, estimates of correlates of protection are elusive because many factors of maternal–fetal immunobiology and disease characteristics must be considered for the estimates. Methods: We developed statistical models that aims to predict vaccine efficacy (VE) in infants following maternal immunization by including quantifiable covariates of the antibody titer distribution of the mother (pre- and post-immunization), the transplacental transfer ratio of IgG antibodies, the rate of antibody decay, and RSV disease incidence rate, all of which are season- and time-dependent and vary by infant age. Result: Our model shows that integrating the lower respiratory tract disease risk based on infant airway diameter and associated airway resistance is critical to appropriately model predicted infant VE. The VE predictions by our models, which preceded maternal RSV prefusion F vaccine efficacy trial primary readouts, closely align with the VE outcomes of these field studies. Conclusion: Our models successfully predicted VE of the RSV maternal vaccines and have potential use in modeling the clinical trial out-comes of other respiratory disease vaccines where maternal antibodies play a role in the protection of newborns. Full article

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections, particularly affecting young infants, older adults, and individuals with comorbidities. Methods: This document, developed as a consensus by an international group of experts affiliated with the World Association of Infectious Diseases and Immunological Disorders (WAidid), focuses on recent advancements in RSV prevention, highlighting the introduction of monoclonal antibodies (mAbs) and vaccines. Results: Historically, RSV treatment options were limited to supportive care and the monoclonal antibody palivizumab, which required multiple doses. Recent innovations have led to the development of long-acting mAbs, such as nirsevimab, which provide season-long protection with a single dose. Nirsevimab has shown high efficacy in preventing severe RSV-related lower respiratory tract infections (LRTIs) in infants, reducing hospitalizations and ICU admissions. Additionally, new vaccines, such as RSVpreF and RSVpreF3, target older adults and have demonstrated significant efficacy in preventing LRTIs in clinical trials. Maternal vaccination strategies also show promise in providing passive immunity to newborns, protecting them during the most vulnerable early months of life. This document further discusses the global burden of RSV, its economic impact, and the challenges of implementing these preventative strategies in different healthcare settings. Conclusions: The evidence supports the integration of both passive (mAbs) and active (vaccines) immunization approaches as effective tools to mitigate the public health impact of RSV. The combined use of these interventions could substantially reduce RSV-related morbidity and mortality across various age groups and populations, emphasizing the importance of widespread immunization efforts. Full article

Background/Objectives: Influenza vaccination is recommended for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza. This study aimed to investigate the impact of body mass index (BMI) on influenza vaccine responses in pregnant women and their newborns. Methods: Participants included pregnant women attending the Women’s and Children’s Hospital in South Australia between 2018 and 2021. Maternal blood samples were collected prior to and at 1 and 6 months post-influenza vaccination to measure antibody responses by hemagglutination inhibition (HI) assay. Cord blood samples were also collected. The percentages of participants achieving HI titre ≥40 were compared between obese and non-obese groups. Results: A total of 73 women were enrolled and received quadrivalent influenza vaccination at a mean age of 32 years (range 21–44 y) and median gestation of 24 weeks (range 11–37 weeks). BMI at vaccination was ≥30 kg/m² for 21/73 women (29%). Most pregnant women demonstrated antibody titres ≥ 40 to all four influenza vaccine strains at 1 month post-vaccination regardless of BMI category (BMI ≥ 30 kg/m²: 19/20; 95% vs. BMI < 30 kg/m²: 47/49; 96%). At 6 months post-vaccination, 12/17 (71%) obese women compared to 36/43 (84%) non-obese women (p = 0.25) maintained HI titres ≥ 40. Cord blood serology showed HI titres ≥ 40 for 11/17 (65%) infants born to mothers with BMI ≥ 30 compared to 30/35 (86%) infants delivered by mothers with BMI < 30 kg/m². Conclusions: A high BMI did not impair influenza vaccine antibody responses in pregnant women at 1 month post-vaccination. However, at 6 months post-vaccination, and in the cord blood samples, the percentages maintaining HI titre ≥ 40 were lower for obese women than for non-obese pregnant women. Full article

Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia. Full article

Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood. Full article