Subamniotic haemorrhage, a possible new presentation of fetal and neonatal alloimmune thrombocytopenia

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare fetal disease in which maternal antibodies directed towards fetal human platelet antigens (HPA) are formed during pregnancy and cause fetal thrombocytopenia. The diagnosis FNAIT is suspected when a fetus or neonate presents with signs of bleeding. Case: We describe a pregnancy complicated by a placental hematoma in the 20th week of gestation as the first manifestation of FNAIT. Further evaluation showed signs of germinal matrix haemorrhage and HPA-5b allo-antibodies. After the diagnosis, intravenous immunoglobulin was administered weekly and a healthy daughter was born at 37 weeks. Histopathological analysis revealed that the hematoma was caused by a subamniotic haemorrhage of fetal origin. Conclusion: A subamniotic hematoma appears to be the first manifestation of FNAIT.

Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

Avian Influenza Virus Status and Maternal Antibodies in Nestling White Ibis (Eudocimus albus)

The White Ibis (Eudocimus albus), a nomadic wading bird, has increased its exploitation of urban habitats in South Florida, United States, and has recently established several urban breeding colonies. Certain characteristics of ibis ecology could position them in the natural cycle of the avian influenza virus (AIV). In fact, experimentally infected ibises were shown to be competent hosts for multiple AIV subtypes, and seroconversion to AIV has been documented in adult ibises in natural populations. However, the mechanisms of transmission and the timing of infection are unclear as we have yet to isolate AIV from a free-living ibis. To investigate the age-specific AIV dynamics of ibis, we captured nestlings (n = 115) weekly for 1–4 weeks from urban and natural settings in 2020 and 2021. We collected choanal/cloacal swabs for rRT-PCR and virus isolation, and plasma to screen for maternal AIV antibodies. AIV was not detected in any individual by virus isolation; however, maternal antibodies to AIV were detected in 95% of nestlings, with varying rates of catabolism. These results confirm that nestlings are afforded maternal antibodies from adults at rates reflective of higher adult seroprevalence than previously documented and that nestlings in breeding colonies may have some degree of protection and are unlikely to become infected with AIV.

Neonatal Rupture of the Tricuspid Valve and Maternal Lupus: Is There a Correlation?

Valve dysfunction is not widely recognized as a feature in newborns born to mothers with positive anti-Ro/SSA antibodies, and only scarce reports have suggested an association between rupture of the atrioventricular valve tensor apparatus and these maternal antibodies. We report the follow-up from fetal life to the time of postnatal surgery of a patient with severe tricuspid regurgitation due to a flail of the anterior tricuspid valve leaflet who was born to an anti-Ro/SSA antibodies positive mother.

Serological Responses to Influenza Vaccination during Pregnancy

Pregnant women, newborns, and infants under six months old are at the highest risk of developing severe and even fatal influenza. This risk is compounded by the inability to vaccinate infants under six months, highlighting the importance of vertically transferred immunity. This review identifies novel insights that have emerged from recent studies using animal models of pregnancy and vaccination. We also discuss the knowledge obtained using existing clinical trials that have evaluated influenza-specific serological responses in pregnant women and how these responses may impact early life immunity. We delineate the mechanisms involved in transferring specific maternal antibodies and discuss the consequences for early life immunity. Most importantly, we highlight the need for continued research using pregnant animal models and the inclusion of pregnant women, a commonly neglected population, when evaluating novel vaccine platforms to better serve and treat communicable diseases.

Repertoire of Naturally Acquired Maternal Antibodies Transferred to Infants for Protection Against Shigellosis

Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age annually worldwide. The incidence of Shigella-induced diarrhea is relatively low during the first year of life and increases substantially, reaching its peak between 11 to 24 months of age. This epidemiological trend hints at an early protective immunity of maternal origin and an increase in disease incidence when maternally acquired immunity wanes. The magnitude, type, antigenic diversity, and antimicrobial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap, Shigella-specific antibodies directed against the lipopolysaccharide (LPS) and virulence factors (IpaB, IpaC, IpaD, IpaH, and VirG), and antibody-mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific (very high levels) and Shigella LPS IgG were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively, and had preferential IgG subclass distribution (protein-specific IgG1 > LPS-specific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied among Shigella serotypes. LPS was identified as the primary target of SBA and OPKA activity. Maternal sera had remarkably elevated Shigella flexneri 2a LPS IgM, indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in a Shigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternally transferred immunity wanes.

Novel Recombinant Newcastle Disease Virus-Based In Ovo Vaccines Bypass Maternal Immunity to Provide Full Protection from Early Virulent Challenge

Newcastle disease (ND) is one of the most economically important poultry diseases. Despite intensive efforts with current vaccination programs, this disease still occurs worldwide, causing significant mortality even in vaccinated flocks. This has been partially attributed to a gap in immunity during the post-hatch period due to the presence of maternal antibodies that negatively impact the replication of the commonly used live vaccines. In ovo vaccines have multiple advantages and present an opportunity to address this problem. Currently employed in ovo ND vaccines are recombinant herpesvirus of turkeys (HVT)-vectored vaccines expressing Newcastle disease virus (NDV) antigens. Although proven efficient, these vaccines have some limitations, such as delayed immunogenicity and the inability to administer a second HVT vaccine post-hatch. The use of live ND vaccines for in ovo vaccination is currently not applicable, as these are associated with high embryo mortality. In this study, recombinant NDV-vectored experimental vaccines containing an antisense sequence of avian interleukin 4 (IL4R) and their backbones were administered in ovo at different doses in 18-day-old commercial eggs possessing high maternal antibodies titers. The hatched birds were challenged with virulent NDV at 2 weeks-of-age. Post-hatch vaccine shedding, post-challenge survival, challenge virus shedding, and humoral immune responses were evaluated at multiple timepoints. Recombinant NDV (rNDV) vaccinated birds had significantly reduced post-hatch mortality compared with the wild-type LaSota vaccine. All rNDV vaccines were able to penetrate maternal immunity and induce a strong early humoral immune response. Further, the rNDV vaccines provided protection from clinical disease and significantly decreased virus shedding after early virulent NDV challenge at two weeks post-hatch. The post-challenge hemagglutination-inhibition antibody titers in the vaccinated groups remained comparable with the pre-challenge titers, suggesting the capacity of the studied vaccines to prevent efficient replication of the challenge virus. Post-hatch survival after vaccination with the rNDV-IL4R vaccines was dose-dependent, with an increase in survival as the dose decreased. This improved survival and the dose-dependency data suggest that novel attenuated in ovo rNDV-based vaccines that are able to penetrate maternal immunity to elicit a strong immune response as early as 14 days post-hatch, resulting in high or full protection from virulent challenge, show promise as a contributor to the control of Newcastle disease.

Waning of Maternal Antibodies against Measles Suggests a Large Window of Susceptibility in Infants in Lao People’s Democratic Republic

Introduction: Measles is an endemic but largely neglected disease in Lao People’s Democratic Republic. New-borns are protected by maternal antibodies, but antibody waning before measles vaccination at 9 months of age leaves infants susceptible to infection. In this study, the susceptibility window of infants was determined to generate scientific evidence to assess the national measles immunization strategy. Methods: Between 2015 and 2016, demographic data, medical history, and blood samples were collected from 508 mother-child pairs at the provincial hospital in Vientiane. The samples were screened with a commercial kit detecting anti-measles IgG antibodies. Results: The large majority (95.7%) of the mothers were seropositive for anti-measles IgG and antibody titers of the mothers and infants were highly correlated (p < 0.01). While at birth 97.7% of the infants were seropositive, seropositivity rates decreased to 74.2% two months later to reach only 28.2% four months after birth (p < 0.01). Just before the first dose of the measles-rubella vaccine, scheduled at 9 months of age, was actually given, less than 14% of the infants were seropositive. Conclusions: This alarmingly wide susceptibility gap due to rapid maternal antibody decay leaves infants at risk of measles infection and serious disease complications. A high herd immunity is crucial to protect young infants and can be achieved through improved routine vaccination coverage and (expanded age group) supplementary immunization activities.

Low-level Plasmodium vivax exposure, maternal antibodies, and anemia in early childhood: Population-based birth cohort study in Amazonian Brazil

Background Malaria causes significant morbidity and mortality in children under 5 years of age in sub-Saharan Africa and the Asia-Pacific region. Neonates and young infants remain relatively protected from clinical disease and the transplacental transfer of maternal antibodies is hypothesized as one of the protective factors. The adverse health effects of Plasmodium vivax malaria in early childhood–traditionally viewed as a benign infection–remain largely neglected in relatively low-endemicity settings across the Amazon. Methodology/Principal findings Overall, 1,539 children participating in a birth cohort study in the main transmission hotspot of Amazonian Brazil had a questionnaire administered, and blood sampled at the two-year follow-up visit. Only 7.1% of them experienced malaria confirmed by microscopy during their first 2 years of life– 89.1% of the infections were caused by P. vivax. Young infants appear to be little exposed to, or largely protected from infection, but children >12 months of age become as vulnerable to vivax malaria as their mothers. Few (1.4%) children experienced ≥4 infections during the 2-year follow-up, accounting for 43.4% of the overall malaria burden among study participants. Antenatal malaria diagnosed by microscopy during pregnancy or by PCR at delivery emerged as a significant correlate of subsequent risk of P. vivax infection in the offspring (incidence rate ratio, 2.58; P = 0.002), after adjusting for local transmission intensity. Anti-P. vivax antibodies measured at delivery do not protect mothers from subsequent malaria; whether maternal antibodies transferred to the fetus reduce early malaria risk in children remains undetermined. Finally, recent and repeated vivax malaria episodes in early childhood are associated with increased risk of anemia at the age of 2 years in this relatively low-endemicity setting. Conclusions/Significance Antenatal infection increases the risk of vivax malaria in the offspring and repeated childhood P. vivax infections are associated with anemia at the age of 2 years.

Repertoire of naturally acquired maternal antibodies transferred to infants for protection against shigellosis

Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age worldwide. The incidence of Shigella-induced diarrhea is relatively low during the first year of life and increases substantially (reaching its peak) between 11 to 24 months of age. This epidemiological trend hints to an early protective immunity of maternal origin and an increase in disease incidence when maternal immunity wanes. The magnitude, type, antigenic diversity and anti-microbial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap, Shigella -specific antibodies directed against the lipopolysaccharide (LPS) and virulent factors (IpaB, IpaC, IpaD, IpaH and VirG) and antibody mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific IgG (very high levels) and Shigella LPS were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively and was associated with IgG subclass distribution (protein-specific IgG1 > LPS-specific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied among Shigella serotypes. LPS was identified as a target of SBA and OPKA activity. Maternal sera had remarkably elevated Shigella flexneri 2a LPS IgM indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in a Shigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternal immunity wanes.