Maternal Antibodies
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2021 ◽  
Sepideh Dolatshahi ◽  
Audrey L Butler ◽  
Christian Pou ◽  
Ewa Henckel ◽  
Anna Karin Bernhardsson ◽  

Abstract Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. Recent studies have shown that while preterm children have an aberrant cellular immune response, these infants receive similar maternal anti-viral IgG repertoires compared to term children, albeit at lower concentrations. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm. To begin to define the mechanism by which preterm selective transfer may occur, the overall quantity and functional quality of an array of vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 preterm and 12 term-delivered mother:infant pairs from birth through week 12. Although higher antibody levels were present in term infants, the overall functional profiles of antigen-specific antibodies were very similar. Temporal transfer differences were ascertained across distinct antibody subpopulations, with early transfer of functional antibodies capable of binding to FcRn and FcγR2-3 receptors followed by the transfer of distinct IgG subclasses. These results provide new insights on maternal:fetal immunity, highlighting novel immune axes that may be manipulated to enhance neonatal immune transfer of antibodies through gestation.

2021 ◽  
Vol 9 (12) ◽  
pp. 2468
Katherine F. Christie ◽  
Rebecca L. Poulson ◽  
Julia Silva Seixas ◽  
Sonia M. Hernandez

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.

Juan M. Carretero Bellon ◽  
Laia Brunet-Garcia ◽  
Joan Sanchez de Toledo ◽  
Stefano Congiu

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.

2021 ◽  
Vol 9 (11) ◽  
pp. 2305
Ana Vazquez-Pagan ◽  
Stacey Schultz-Cherry

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.

2021 ◽  
Vol 14 (11) ◽  
pp. e246590
Filipa Costa Cascais ◽  
Sofia Fraga ◽  
Sandra Sousa ◽  
Margarida Pinto

Neonatal lupus is an uncommon entity. The main manifestations are cutaneous and cardiac. It is caused by transplacental passage of maternal antibodies (anti-Ro/SSA or anti-La/SSB), and the diagnosis is made by its detection in the mother or child. The authors present a case of a 4-month-old female infant, with a cutaneous eruption since she was 2 months old. She had no relevant personal or family history. Analytically she had an increase in liver enzymes. The histological aspect of the skin biopsy led to an autoimmunity study on the mother and infant, both of which had positive anti-Ro/SSA antibodies, confirming the diagnosis of neonatal lupus. Cardiological study was normal. The skin lesions resolved during the first year of life. Skin lesions are the most frequent non-cardiac clinical manifestation of neonatal lupus, and they are self-limited. When there is no family history, nor cardiac involvement, the diagnosis can be challenging.

2021 ◽  
Vol 14 (11) ◽  
pp. e246747
Sakviseth Bin ◽  
Rathmony Heng ◽  
Sethikar IM

The most common cause of congenital heart block (CHB) is neonatal lupus, an acquired autoimmune disease caused by transplacental transfer of maternal antibodies to the fetus. A full-term female neonate was admitted to neonatal intensive care unit for severe bradycardia with stable haemodynamics. The mother, showing no clinical symptoms or any particular history, was transferred to our tertiary centre for profound fetal bradycardia. At birth, the infant’s ECG showed a third-degree atrioventricular block and echocardiography was normal. Cardiac neonatal lupus was confirmed with positive maternal anti-Ro antibodies. Under close monitoring, the infant tolerated the bradycardia well (median 67 beats per minute (bpm)) and was discharged on day 6 of life. There was no indication for pacemaker, but she would be on regular follow-up with a paediatric cardiologist. This article holds an important insight as it is the first confirmed case of autoimmune CHB in Cambodia in which the mother’s antibody was found only after diagnosis on the neonate.

2021 ◽  
Kevin C Ma ◽  
Jaime E Hale ◽  
Yonatan Grad ◽  
Galit Alter ◽  
Katherine Luzuriaga ◽  

Background. Estimating the cumulative incidence of SARS-CoV-2 is essential for setting public health policies. We leveraged de-identified Massachusetts newborn screening specimens to generate an accessible, retrospective source of maternal antibodies for estimating statewide SARS-CoV-2 seroprevalence in a non-test-seeking population. Methods. We analyzed 72,117 newborn dried blood spots collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the general Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification. Results. Statewide seroprevalence was estimated to be 0.03% (90% credible interval (CI) [0.00, 0.11]) in November 2019 and rose to 1.47% (90% CI [1.00, 2.13]) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onwards, reaching 2.15% (90% CI [1.56, 2.98]) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = 0.024, 90% CI [0.004, 0.044]); i.e., a 10% increase in community percent non-Hispanic Black was associated with a 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter. Conclusions. Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable.

2021 ◽  
Vol 12 ◽  
Esther Ndungo ◽  
Liana R. Andronescu ◽  
Andrea G. Buchwald ◽  
Jose M. Lemme-Dumit ◽  
Patricia Mawindo ◽  

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.

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1189
Kiril M. Dimitrov ◽  
Tonya L. Taylor ◽  
Valerie C. Marcano ◽  
Dawn Williams-Coplin ◽  
Timothy L. Olivier ◽  

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.

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1316
Phonepaseuth Khampanisong ◽  
Maude Pauly ◽  
Phonethipsavanh Nouanthong ◽  
Molly A. Vickers ◽  
Siriphone Virachith ◽  

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.

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