Placental Transfer Of Antibodies Research Articles

Regulators of placental antibody transfer through a modeling lens.

Infants are vulnerable to infections owing to a limited ability to mount a humoral immune response and their tolerogenic immune phenotype, which has impeded the success of newborn vaccination. Transplacental transfer of IgG from mother to fetus provides crucial protection in the first weeks of life, and maternal immunization has recently been implemented as a public health strategy to protect newborns against serious infections. Despite their early success, current maternal vaccines do not provide comparable protection across pregnancies with varying gestational lengths and placental and maternal immune features, and they do not account for the dynamic interplay between the maternal immune response and placental transfer. Moreover, progress toward the rational design of maternal vaccines has been hindered by inadequacies of existing experimental models and safety challenges of investigating longitudinal dynamics of IgG transfer in pregnant humans. Alternatively, in silico mechanistic models are a logical framework to disentangle the processes regulating placental antibody transfer. This Review synthesizes current literature through a mechanistic modeling lens to identify placental and maternal regulators of antibody transfer, their clinical covariates, and knowledge gaps to guide future research. We also describe opportunities to use integrated modeling and experimental approaches toward the rational design of vaccines against existing and emerging neonatal pathogen threats.

Maternal Immunization with Adjuvanted Recombinant Receptor-Binding Domain Protein Provides Immune Protection against SARS-CoV-2 in Infant Monkeys.

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants' IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine.

Vaccines for Streptococcus agalactiae: current status and future perspectives.

A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.

Seroprevalence and placental transfer of SARS-CoV-2 antibodies in unvaccinated pregnant women

PurposePregnant women are at risk of severe SARS-CoV-2 infection, potentially leading to obstetric and neonatal complications. Placental transfer of antibodies directed to SARS-CoV-2 may be protective against neonatal COVID-19, but this remains to be studied. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a population of unvaccinated pregnant women and to determine the placental transfer of these antibodies.MethodologyA total of 1197 unvaccinated women with mostly unknown pre-study SARS-CoV-2 infection status, were tested at delivery for SARS-CoV-2 spike protein IgG antibodies during the first year of the pandemic. Umbilical cord samples were collected and assessed for seropositivity if the mother was seropositive. Maternal characteristics, pregnancy and neonatal outcomes and data on SARS-CoV-2 infection were extracted from medical records.ResultsSpecific IgG were detected in 258 women (21.6%). A significant placental transfer to the newborn was observed in 81.3% of cases. The earlier in the 2nd and 3rd trimesters that the mother had contracted the disease and the more symptomatic she was, the greater the likelihood of transplacental transfer of IgG to her newborn.ConclusionApproximately one in five women had detectable anti-SARS-CoV-2 spike protein IgG antibodies at delivery during the first year of the pandemic, and these antibodies were significantly transferred to their fetuses. This research provides further evidence to better understand the dynamics of the placental transfer of SARS-CoV-2 IgG antibodies from mothers to their newborns, which is necessary to improve vaccination strategies.

Effects of the timing of maternal SARS-CoV-2 infection and vaccination status on placental transfer of antibodies to neonates: A cross-sectional study

ObjectivesTo assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. MethodsIn this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. ResultsThe group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the <90 days group (β= 0.33, 95%CI: 0.01-0.65). Neonatal IgG titers correlated significantly with maternal titers and with maternal infections more than 90 days before delivery. Among infected pregnant women, those who had received 2 or 3 doses of vaccine before pregnancy had higher neonatal antibody titers than those who were not vaccinated (β = 57.70, 95%CI: 31.33-84.07). ConclusionNeonates born to pregnant women who were vaccinated before infection showed higher antibody titers than neonates of pregnant women who were not vaccinated before infection. The transfer rate is higher in pregnant women with ≥90 days from infection to delivery than in those with <90 days. These findings highlight the importance of timely maternal vaccination to optimize maternal and infant immunity.

Transplacental transfer of maternal antibodies following immunization with recombinant pertussis vaccines during pregnancy: Real-world evidence

Aim/objectiveThis study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. MethodsThis postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aPgen; n = 199) or combined to tetanus-diphtheria (TdaPgen; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed. ResultsNo adverse pregnancy, delivery, or neonatal outcomes attributed to aPgen, TdaPgen, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aPgen (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaPgen (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels. ConclusionThis first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants.Thai Clinical Trial Registry: TCTR20200528006.

Analysis of the transplacental transmission of SARS CoV-2 virus and antibody transfer according to the gestational age at maternal infection

To quantify transplacental transmission of SARS-CoV-2 virus and antibody transfer in pregnant women and their newborns according to the gestational age at maternal infection. A prospective observational multicenter study including pregnant women with a positive RT-PCR or a positive serology for SARS-CoV-2 and compatible symptoms, from April to December 2020, in 11 French maternities. The study was designed to obtain a systematic collection of mother-infant dyad’s samples at birth. SARS-CoV-2 viral load was measured by RT-PCR. IgG and IgM antibodies against the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed according to the gestational age at maternal infection. The primary outcome was the rate of SARS CoV-2 materno-fetal transmission at birth. The secondary outcome was the quantification of materno-fetal antibody transfer. Maternal and neonatal outcomes at birth were additionally assessed. Among 165 dyads enrolled, one congenital infection was confirmed {n = 1 (0.63%) IC95% [0.02%; 3.48%]}. The average placental IgG antibody transfer ratio was 1.27 (IC 95% [0.69–2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P Value = 0.0001). Maternal and neonatal outcomes were reassuring. We confirmed the very low rate of SARS-CoV-2 transplacental transmission (< 1%). Maternal antibody transfer to the fetus was more efficient when the infection occurred during the first and second trimester of pregnancy.

COVID-19 Maternal Antibody Concentrations in Small for Gestational Age Infants: Does Placental Insufficiency Impact Transplacental Antibody Transfer?

COVID-19 Maternal Antibody Concentrations in Small for Gestational Age Infants: Does Placental Insufficiency Impact Transplacental Antibody Transfer?

Placental Transfer Efficiency of Neutralizing Antibodies on SARS-CoV-2 Vaccination before and after Pregnancy in Mexican Women.

The protection of the neonate against pathogens depends largely on the antibodies transferred placentally from the mother; for this reason, maternal vaccination against emerging viruses, such as SARS-CoV-2, is of vital importance. Knowing some of the immunogenic factors that could alter the placental transfer of antibodies could aid in understanding the immune response and neonatal protection after maternal vaccination. In this study, we analyzed the efficiency of the placental transfer of binding and neutralizing antibodies, as well as some factors that could alter the passive immune response, such as the trimester of gestation at the time of immunization, the number of doses received by the mother and the type of vaccine. Binding IgG antibodies were detected by ELISA, and the detection of neutralizing antibodies was carried out using flow cytometry. Our results show efficient transfer rates (>1), which are higher when maternal vaccination occurs during the third trimester of gestation. Antibodies are detectable in mothers and their neonates after 12 months of maternal immunization, suggesting than the vaccination against COVID-19 before and during pregnancy in the Mexican population induces a lasting neutralizing response in mothers and their newborns.

Chapter 12 - Myasthenia gravis

Myasthenia gravis (MG) is a rare neuromuscular junction disorder that is characterized by fatigable weakness of muscles. People with MG experience various clinical manifestations based on the muscles involved. MG can be autoimmune, paraneoplastic, congenital, medication-related, or transient in the neonatal period due to the passive placental transfer of antibodies from mothers with MG. Acetylcholine receptor antibodies are seen in the majority of patients with MG. However, other antibodies have been discovered in the last 20 years, including muscle-specific tyrosine kinase (MuSK) and lipoprotein-related peptide 4 (LRP4), and are now available through commercial testing. More recently, a handful of other antibodies have been associated with MG; however, they are not presently available for routine testing. A disease classification system has been developed by the Myasthenia Gravis Foundation of America (MGFA) and is commonly used worldwide. A number of objective and subjective outcome measures have been developed and validated over the years and have been proven useful for both clinical and research purposes, serving as primary and secondary outcome measures in most clinical trials. A growing number of therapies are available for both acute and chronic management of MG, with several new mechanistic approaches under investigation. An international consensus guidance for the management of MG was first published in 2016 and updated in 2020.

Maternal Seroprevalence and Placental Transfer of COVID-19 Antibodies in Pregnancy: A Hospital-Based Study.

Coronavirus disease 2019 (COVID-19) is a relatively new disease with high morbidity and mortality.Information about the prevalence of infections in pregnancy could help identify herd immunity, project epidemics, and decide policy guidelines. The aim of this study was to determine the infection susceptibility risk of COVID-19 in pregnancy, to determine the prevalence of COVID-19 antibodies (IgG & IgM), and to evaluate the determinants of COVID-19 antibody positivity in pregnancy. This was an analytical cross-sectional study involving 258 consenting pregnant women recruited at Irrua Specialist Teaching Hospital, Edo State, Nigeria. Of these, 179 participants were recruited from the antenatal clinic, and 79 from the gynecology emergency unit. A structured questionnaire was administered at baseline. Venous blood was obtained at enrolment to test for total antibodies using ELISA. A nasopharyngeal swab was simultaneously obtained for COVID-19 PCR for all participants. Umbilical cord blood was taken after delivery in those who had positive serology. Socio-demographic variables and clinical presentation of respondents were considered as exposure variables, and this was cross-tabulated with outcome variables in bivariate analysis using chi-square with a level of significance at a P-value less than 0.05. Variables in bivariate analysis of chi-square that have a P-value less than 0.2 were entered into a logistic regression using multivariate logistic models. The study detected active COVID-19 infections among 7.4% (19/258) of the study participants. The study demonstrated a seroprevalence of COVID-19 antibodies in 62.4% (161/258) of the participants at recruitment and showed a strong correlation between working in the healthcare setting and living in an urban environment. Our study also reported 5.3% (8/152) of cord blood antibody positivity among study participants. The concentration of maternal immunoglobulin strongly and positively correlated with cord blood seropositivity. Prevalence estimates are an underestimate of the actual proportion of pregnant women with prior COVID-19 exposure as observed in the study discrepancy of confirmed PCR infection and evidence of previous infection from serology. The study also highlighted a low efficiency of placental transfer of COVID-19 antibodies at birth among those who were seropositive at baseline and showed that maternal antibody levels play an important role in determining the efficiency of placenta transfer of COVID-19 antibodies in pregnancy.

Acquisition of complement fixing antibodies targeting Plasmodium falciparum merozoites in infants and their mothers in Uganda.

Antibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear. We measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants' complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years. Infants with high levels at birth experienced a faster decay of complement-fixing antibodies but showed similar levels to the low response group of newborns thereafter. No difference was observed in antibody levels between infant cord blood and mothers at delivery. The same result was found when categorized into high and low response groups, indicating placental transfer of antibodies. Complement-fixing antibodies were positively correlated with total schizont-specific IgG and IgM levels in mothers and infants at several time points. At nine months, complement-fixing antibodies were negatively correlated with total B cell frequency and osteopontin concentrations in the infants, while positively correlated with atypical memory B cells and P. falciparum-positive atypical memory B cells. This study indicates that complement-fixing antibodies against P. falciparum merozoites are produced in the mothers and placentally-transferred, and they are acquired in infants over time during the first years of life. Understanding early life immune responses is crucial for developing a functional, long lasting malaria vaccine.

1624. SARS-CoV-2 Maternal Vaccination Induces More Efficient Placental Antibody Transfer to Newborns than SARS-CoV-2 Infection During Pregnancy

Abstract Background Passive immunization via maternal antibodies (Ab) is a key mechanism for infant protection in early life. This study analyzed the landscape of passive immunization induced by SARS-CoV-2 infection and/or vaccination by comparing the magnitude and durability of the transferred Ab. Methods Prospective multicenter observational cohort study of SARS-CoV2-infected and/or vaccinated pregnant women and their infants. We collected maternal and cord blood samples at delivery and neonatal/infant samples at delivery, and at 1, 2, 6 and 12 months (mo) of age. RBD and Spike IgG Ab titers were measured by ELISA. Results 215 mothers (infected=106, vaccinated=67, infected and vaccinated=42) and 174 infants (n=87, n=54, n=33, respectively) were enrolled. At birth RBD Ab titers median [IQR] of infants from vaccinated mothers [4.28 (3.48-4.80)] log10 ng/ml and from infected and vaccinated mothers [4.61 (4.27-4.93)] log10 ng/ml were higher than those from infected mothers [2.20 (0.10-3.30)] log10 ng/ml, p&amp;lt; 0.001. These differences were observed until 6 mo of age, when only 1/13 (7.7%) infant from infected mothers had detectable maternal Ab compared to 14/15 (93.3%) and 8/8 (100%) from the vaccinated, and infected and vaccinated groups, respectively. At 12 mo none of the infants born to infected mothers had detectable maternal Ab, while in the vaccinated group (n=11), 3 (27.3%) had persistent Ab, and 4 (36.4%) suspected infection. At 12 mo in the infected and vaccinated group (n=6) 3 had no Ab, and 3 had suspected infection. The median [IQR] placental Ab transfer ratio was higher in the vaccinated only group (2.94 [1.34-3.74]) than the infected only group (1.19 [0.33-2.52]) p&amp;lt; 0.01. Linear regression analyses demonstrated that the mean RBD Ab transfer ratio for infants from vaccinated vs infected women was 1.76 (95% CI=1.07-2.88, p=0.025) higher after adjusting for trimester of infection or vaccination. Similar results were observed with Spike Ab. Demographic and clinical characteristics of the study population m; median. IQR; interquartile range. N/A; not applicable. Figure 1. Comparison of RBD antibody titers in infected, vaccinated and infected and vaccinated groups at the time of delivery (from maternal blood, cord blood and neonatal blood) and at months 1, 2, 6 and 12 from neonatal/infant blood. Figure 2. Correlation between maternal and neonatal RBD antibody titers in groups of infected, vaccinated and infected and vaccinated mothers. These correlations also represent the values of the antibody transfer ratios across the placenta. While the bisector (red line) represents the values for a transfer ratio (TR) = 1, all values above it would correspond with TR&amp;gt;1 and those below with TR &amp;lt; 1. Green dots represent the infected group, the blue dots the vaccinated group, and the orange dots the infected and vaccinated group. Conclusion Infants from vaccinated mothers demonstrated maternal Ab up to 6 mo with higher titers than infants born from infected mothers. Antibodies generated by vaccination were transferred more efficiently than those generated by infection regardless of the trimester in which occurred. Disclosures Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant Octavio Ramilo, MD, AstraZeneca: Honoraria|Bill &amp; Melinda Gates Foundation: Grant/Research Support|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria

Immunomodulation of Antibody Glycosylation through the Placental Transfer

Establishing an immune balance between the mother and fetus during gestation is crucial, with the placenta acting as the epicenter of immune tolerance. The placental transfer of antibodies, mainly immunoglobulin G (IgG), is critical in protecting the developing fetus from infections. This review looks at how immunomodulation of antibody glycosylation occurs during placental transfer and how it affects fetal health. The passage of maternal IgG antibodies through the placental layers, including the syncytiotrophoblast, stroma, and fetal endothelium, is discussed. The effect of IgG subclass, glycosylation, concentration, maternal infections, and antigen specificity on antibody transfer efficiency is investigated. FcRn-mediated IgG transport, influenced by pH-dependent binding, is essential for placental transfer. Additionally, this review delves into the impact of glycosylation patterns on antibody functionality, considering both protective and pathological effects. Factors affecting the transfer of protective antibodies, such as maternal vaccination, are discussed along with reducing harmful antibodies. This in-depth examination of placental antibody transfer and glycosylation provides insights into improving neonatal immunity and mitigating the effects of maternal autoimmune and alloimmune conditions.

Development of A Standardized Opsonophagocytosis Killing Assay for Group B Streptococcus and Assessment in an Interlaboratory Study

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65–3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies.

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies.

Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient's anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.

Proof of concept for a single-dose Group B Streptococcus vaccine based on capsular polysaccharide conjugated to Qβ virus-like particles

A maternal vaccine to protect neonates against Group B Streptococcus invasive infection is an unmet medical need. Such a vaccine should ideally be offered during the third trimester of pregnancy and induce strong immune responses after a single dose to maximize the time for placental transfer of protective antibodies. A key target antigen is the capsular polysaccharide, an anti-phagocytic virulence factor that elicits protective antibodies when conjugated to carrier proteins. The most prevalent polysaccharide serotypes conjugated to tetanus or diphtheria toxoids have been tested in humans as monovalent and multivalent formulations, showing excellent safety profiles and immunogenicity. However, responses were suboptimal in unprimed individuals after a single shot, the ideal schedule for vaccination during the third trimester of pregnancy. In the present study, we obtained and optimized self-assembling virus-like particles conjugated to Group B Streptococcus capsular polysaccharides. The resulting glyco-nanoparticles elicited strong immune responses in mice already after one immunization, providing pre-clinical proof of concept for a single-dose vaccine.

Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study

Minimal data exist on pregnancy following recovery from Ebola in people of child-bearing potential (females aged roughly 18-45 years). The aim of this study was to assess viral persistence or reactivation in pregnancy, the frequency of placental transfer of anti-Ebola IgG antibodies, and pregnancy outcomes in this population. In this observational cohort study, we studied self-reported pregnancies in two groups: seropositive people who had recovered from Ebola virus disease (seropositive group) and seronegative people who had close contact with people with Ebola (seronegative group). Participants had enrolled in the PREVAIL III longitudinal study and were exposed during the 2014-2016 Liberian Ebola outbreak. The primary outcome was pregnancy result. We assessed rates of livebirths and other pregnancy results in both study groups, and presence of Ebola RNA by PCR in samples of placenta, maternal and cord blood, breastmilk, and vaginal secretions from people who had recovered from Ebola who conceived a median of 14 months after acute Ebola virus disease. Mixed-model logistic regression evaluated associations between first-reported pregnancy outcome, age, and study group. Growth and neurodevelopment in the infants born to people in the seropositive group were assessed at 6-month intervals for 2 years. Data were accrued by PREVAIL III study staff. 1566 participants were enrolled between June 17, 2015, and Dec 14, 2017, of whom 639 became pregnant (215 seropositive, 424 seronegative) and 589 reported pregnancy outcomes (206 seropositive, 383 seronegative). 105 infants born to 98 mothers in the seropositive group were enrolled in the birth cohort. Ebola RNA was not detected in 205 samples of placenta, cord blood, or maternal blood taken at birth from 54 mothers in the seropositive group, nor in 367 vaginal swabs. Viral RNA was found in two of 354 longitudinal breastmilk samples. All but one of 57 infants born during these 54 births were seropositive for anti-Ebola antibodies. Neonates showed high concentrations of anti-Ebola IgG, which declined after 6 months. Odds of adverse pregnancy outcome among the two groups were indistinguishable (OR 1·13, 95% CI 0·71-1·79). Compared with WHO standards, infants born to those in the seropositive group had lower median weight and length, and larger median head circumference over 2 years. Compared with a cohort from the USA accrual of gross motor developmental milestones was similar, whereas attainment of pincer grasp and early vocalisation were mildly delayed. The risks of Ebola virus reactivation in the peripartum and postpartum period and of adverse birth outcomes are low in those who have recovered from Ebola virus disease and become pregnant approximately 1 year after acute Ebola virus disease. The implication for clinical practice is that care of people who are pregnant and who have recovered from Ebola can be offered without risks to health-care providers or stigmatisation of the mothers and their offspring. The implication for prospective mothers is that safe pregnancies are entirely possible after recovery from Ebola. National Institute of Allergy and Infectious Diseases and Liberia Ministry of Health.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

The Postpartum Period Can Worsen Myelin Oligodendrocyte Glycoprotein Antibody-associated Encephalomyelitis: A Case Report.

Myelin oligodendrocyte glycoprotein (MOG) antibodies are associated with relapsing inflammatory demyelinating disease. Pregnancy complicates the disease course, potentially leading to either symptom improvement or worsening. A 28-year-old woman with MOG antibody-associated encephalomyelitis had 2 pregnancies; her disease worsened during both postpartum periods despite continuing prednisolone and levetiracetam. The umbilical cord blood was positive for MOG antibodies following her second pregnancy, but neither baby had MOG antibody-associated disease. This is the first case report of MOG antibody-associated demyelinating disease that worsened postpartum despite continuous medication. Furthermore, we observed the placental transfer of MOG antibodies for the first time.