Transplacental Antibody Transfer Research Articles

The utility of phospholipase A2 receptor antibody in pregnancy: A case report

Primary membranous nephropathy remains a rare but challenging condition to manage in pregnancy. We present a case of an unplanned pregnancy in a 35-year-old woman with PLA2R-antibody positive membranous nephropathy, who had demonstrated serological response to rituximab given three months prior to pregnancy (PLA2R 115 IUmL reducing to 2 IU/mL, normal <13.9 IU/mL)). Throughout pregnancy, serial measurements of proteinuria and PLA2R-antibodies were used to understand disease activity and inform the decision to escalate treatment. Delivery of a healthy male infant occurred at 34 weeks, due to threatened pre-eclampsia and reduced fetal growth. There was evidence of trans-placental transfer of antibodies (15.2 IU/mL – normal <13.9 IU/mL) but no associated nephrotic syndrome in the infant. This case highlights the potential of PLA2R antibody as a diagnostic and monitoring tool during pregnancy, and adds to a small body of literature around the consequences of fetal–maternal transfer of the PLA2R antibody.

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.

Association Between Influenza Vaccination During Pregnancy and Infant Influenza Vaccination

(Obstet Gynecol. 2023;141:563–569) Vaccines are safe and effective in preventing illness, including in mildly immunosuppressed individuals such as pregnant women. Influenza vaccines have been in use for decades and have been shown to be safe and effective at preventing illness in both mother and child, providing protection through the transplacental transfer of antibodies to infants too young to receive their own vaccination. Influenza presents increased risks to pregnant individuals as well as adverse outcomes for fetuses and infants. Annual influenza vaccinations are recommended for everyone 6 months and older, but rates of annual vaccinations are chronically low. This study was designed to evaluate the association between influenza vaccination during pregnancy and infant influenza vaccination.

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?

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm

COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (β = 0.44; 95% CI, -0.06 to 0.94). In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.

Effectiveness of Covid-19 Vaccine in Pregnant Women: A Systematic Review

The newly developed COVID-19 vaccine faces public's concerns in terms of its effectiveness and safety as an approach in combating COVID-19 pandemic. It is well-established that COVID-19 vaccine is effective alongside being the most promising approach against COVID-19 infection in both general and vulnerable populations. This study aims to evaluate the effectiveness of COVID-19 vaccine in pregnant women as a subgroup of vulnerable population by analysing several important immunological parameters in pregnant women. Specifically, it investigates how effective the COVID-19 vaccine will reduce the infection rate and how it will affect the mothers' antibody levels against SARS-CoV-2. In this study, the immunological parameters investigated are maternal antibody response against SARS-CoV-2 and the transplacental transfer of the antibody. To test the hypothesis that COVID-19 vaccine is effective in pregnant women, a systematic review was conducted on previous studies regarding COVID-19 vaccine and its outcomes in pregnancy. Results were narratively analysed. The results showed reduced COVID-19 infection rate, elevated maternal antibody titre against SARS-CoV-2 and positive transplacental anti-SARS-CoV-2 IgG antibody transfer in vaccinated pregnant women in comparison to unvaccinated pregnant women. These results suggest that COVID-19 vaccine is highly effective against COVID-19 infection in pregnant women. Furthermore, COVID-19 vaccine not only elicits sufficient maternal antibody response as an immunity for mothers against COVID-19 infection but also provides similar protection for infants via passive immunity by means of transplacental antibody transfer. In conclusion, the uptake of COVID-19 vaccine and future booster dose by pregnant women should be strongly encouraged due to its favourable outcomes and protection against COVID-19 disease.

Transplacental Transfer Efficiency of SARS-CoV-2-Specific IgG Antibodies in Iranian Seropositive Mothers: A Monocentric Study in Karaj, Iran

Background: Passively acquired maternal antibodies through the placenta and/or breastfeeding may protect neonates against SARS-CoV-2 before they are considered eligible for active immunization. Objectives: This study aimed to determine the concentration and correlation of maternal and cord blood anti-SARS-CoV-2 IgG antibodies in Iranian seropositive women. In this preliminary study, attempts were also made to assess the effects of some variables on the transplacental transfer efficiency. Methods: From September 2021 to November 2021, pregnant women presenting to Kamali Hospital in Karaj, Iran, were enrolled in this monocentric study. The maternal and neonatal demographic characteristics were collected. The maternal and cord blood spike protein-specific antibody levels, measured at delivery (119 paired samples), were evaluated by the enzyme-linked immunosorbent assay (ELISA). Results: Based on the transplacental antibody transfer ratios, the participants were divided into 2 groups: Transfer ratio ≤ 1 (n = 53) and transfer ratio &gt; 1 (n = 66). The results revealed that anti-SARS-CoV-2 IgG antibodies were transferred across the placenta in all seropositive pregnant Iranian women, and a significant correlation was found between maternal and cord blood-specific IgG antibody levels (r = 0.9646; P &lt; 0.05). A relatively efficient transplacental transfer ratio was observed in Iranian seropositive women (transfer ratio &gt; 1 in 66 out of 119 individuals; 55.46%). Although there were significant differences in the transplacental transfer ratio regarding the neonatal birth weight and maternal body mass index (BMI), more extensive investigations with a larger sample size are needed to confirm the significant association of these variables with the transplacental transfer efficiency of specific SARS-CoV-2 IgG antibodies. Conclusions: The present study highlighted the importance of vaccination during pregnancy to improve neonatal immune responses against SARS-CoV-2.

478. COVID-19 maternal antibody concentrations in twin infants: impact of multiple pregnancy on transplacental antibody transfer during pregnancy

Abstract Background COVID-19 vaccines in pregnancy protect both pregnant individuals and young infants from severe illness via transplacental transfer of maternally-derived IgG. However, the impact of multiple (e.g. twin) pregnancy on transplacental transfer of SARS-CoV-2 IgG is unknown. We aimed to evaluate anti-Spike (S) antibody transfer among infants from twin pregnancies compared to singleton pregnancies. Methods We conducted a prospective cohort study among individuals with twin and singleton pregnancies who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery. We tested paired maternal and cord samples for anti-S IgG and used linear regression to evaluate associations between multiple or singleton pregnancy and anti-S antibody. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age (&amp;lt; 10th percentile) birthweight. Results We tested maternal/cord anti-S IgG from 25 twin and 291 singleton pregnancies. The median gestational age at delivery was 36 weeks for twin infants compared to 39 weeks for singleton infants. Median maternal anti-S IgG was 5812 BAU/mL (IQR:754, 16061) and 2971 BAU/mL (IQR:706, 14000) for twin and singleton pregnancies, respectively. Median cord anti-S IgG was 4110 BAU/mL (IQR: 527, 15937) and 3636 BAU/mL (IQR: 1019, 15465) for twin and singleton infants, respectively (Figure 1). Cord:maternal IgG ratios were significantly lower in twin pregnancies compared to singleton pregnancies (p &amp;lt; 0.01; Figure 2). After adjustment for covariates, there was no difference between maternal anti-S IgG concentrations (beta: -0.54; 95% confidence interval [CI]: -1.26,0.18; p=0.14), cord anti-S IgG concentrations (beta: -0.77; 95% CI: -1.68,0.13; p=0.10) or cord:maternal IgG ratios (beta: -0.07; 95% CI: -0.32,0.19; p=0.61) between twin and singleton pregnancies. Conclusion Twin and singleton infants benefit similarly from maternal COVID-19 vaccine during pregnancy. Higher risk pregnancies including multiple pregnancies should be considered in health policy discussions regarding COVID-19 vaccine timing in pregnancy. Disclosures Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

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.

Alloimmune hemolytic disease of the fetus and newborn: genetics, structure, and function of the commonly involved erythrocyte antigens.

Hemolytic disease of the fetus and newborn (HDFN) can occur when a pregnant woman has antibody directed against an erythrocyte surface antigen expressed by her fetus. This alloimmune disorder is restricted to situations where transplacental transfer of maternal antibody to the fetus occurs, and binds to fetal erythrocytes, and significantly shortens the red cell lifespan. The pathogenesis of HDFN involves maternal sensitization to erythrocyte "non-self" antigens (those she does not express). Exposure of a woman to a non-self-erythrocyte antigen principally occurs through either a blood transfusion or a pregnancy where paternally derived erythrocyte antigens, expressed by her fetus, enter her circulation, and are immunologically recognized as foreign. This review focuses on the genetics, structure, and function of the erythrocyte antigens that are most frequently involved in the pathogenesis of alloimmune HDFN. By providing this information we aim to convey useful insights to clinicians caring for patients with this condition.

Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy

Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3months old but only 1.1% (1 of 92) of patients≥21months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.

Effects of maternal HIV infection on early Kaposi's sarcoma-associated herpesvirus (KSHV) seroconversion in a Kenyan mother-infant cohort.

We identified whether maternal HIV infection during pregnancy affects transplacental transfer of Kaposi's sarcoma-associated herpesvirus (KSHV) specific antibodies and subsequent infant infection. We followed pregnant Kenyan women through delivery and their infants until age two years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status. Maternal venous and cord blood at delivery and child venous blood every six months were tested for antibodies to 20 KSHV antigens by multiplex bead-based immunoassay. Multiple comparisons were adjusted using false discovery rate (FDR). Maternal HIV infection was significantly associated with decreased transplacental transfer of antibodies against all KSHV antigens and lower cord blood levels for eight antigens at FDR p<0.10. Neither birth to six-month antibody level changes nor six-month levels differed in HEU and HUU, except for ORF50. 74% of children KSHV seroconverted by age 24 months but HEU and HUU did not differ in time to seroconversion nor two-year seropositivity after adjustment for child malaria infection. Maternal HIV infection reduced a child's initial KSHV antibody levels but did not affect age of infection. Regardless of HIV exposure in utero, KSHV seroconversion in Kenyan children occurred early; associated factors must be identified.

A narrative review of COVID-19 vaccination in pregnancy and breastfeeding.

The Coronavirus pandemic has affected millions of people due to the spread of the Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) virus. Pregnant individuals and infants are most vulnerable given the increased risk of developing severe complications from SARS-CoV-2 infection. Recently, COVID-19 vaccination is recommended for pregnant women and infants starting at 6 months of age to prevent disease contraction and minimize disease severity. We conducted a review of the literature on COVID-19 vaccination to discuss vaccine safety and efficacy, immunity after maternal vaccination, transplacental transfer and persistence of antibodies, and public health implications. Current evidence supports the safety and efficacy of vaccination during pregnancy. Maternal vaccination provides greater antibody persistence in infants compared to immunity from natural infection. Furthermore, vaccination has demonstrated an increased rate of passive antibody transfer through the placenta and breast milk. Public health interventions are important in achieving herd immunity and ultimately ending the pandemic. IMPACT: This article highlights the benefits of COVID-19 vaccination during pregnancy with a review of the data describing safety and efficacy, passive and active immunity after maternal immunization, trans-placental transfer and persistence of protective antibodies, and public health implications. With this information, healthcare providers can provide up-to-date knowledge to their pregnant patients to help them form an informed decision on vaccination and combat vaccine hesitancy.

Transient Neonatal Myasthenia Gravis: Case Report

Purpose: Transient neonatal myasthenia gravis (NMG) results from the transplacental transfer of antibodies of mothers with an autoimmune form of myasthenia gravis. The clinical presentation develops in 10%–20% of their children. This study aimed to present a case of a newborn with transient myasthenia gravis (MG) born to a mother diagnosed with MG.&#x0D; Case presentation: The disease manifested itself as generalized hypotonia, weak cry, respiratory distress, poor sucking, and facial diplegia. The symptoms were usually self-limiting, and transient supportive treatment was required. A diagnostic test was a good clinical response of the child to the administration of an acetylcholinesterase inhibitor. After the clearance of antibodies from the child's blood, long-term therapy was not necessary and the disease resolved. Treatment was supportive and included the administration of smaller and more frequent meals via a tube, noninvasive or invasive support of respiratory function, and use of acetylcholinesterase inhibitors (neostigmine and pyridostigmine).&#x0D; Conclusion: Pediatric patients diagnosed with transient NMG are extremely rare in everyday clinical practice, and hence it is important to be familiar with it.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 IgG Is Present in the Amniotic Fluid of both Infected and Vaccinated Women at Second Trimester of Pregnancy: A Cohort Study

Introduction: Pregnant women are protected from the complications of COVID-19 infection, thanks to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The benefit of this vaccination to prevent morbidity and mortality in the fetus has not yet been completely elucidated. Our aim was to test the presence of anti-SARS-CoV-2 antibodies in the amniotic fluid during the second trimester of pregnancy and then to compare them to the antibody levels in maternal serum to evaluate their correlation and to improve amniotic fluid immunological characteristics knowledge. Methods: This cohort study took place at the Policlinico G. Martino of Messina from September 2021 to February 2022; 22 pregnant women had amniocentesis: we analyzed serum and amniotic fluid samples of women who contracted the SARS-CoV-2 infection or vaccinated against the same virus within 1 year, and women never infected or vaccinated against it. Amniotic fluids and peripheral blood were collected to evaluate IgG anti-SARS-CoV-2 nucleocapsid and spike S1 protein antibodies. Results: Patients vaccinated had higher S1 receptor-binding domain antibody levels both in amniotic fluid (p < 0.006; mean 68.70; standard deviation [SD] 85.46) and maternal blood (p < 0.005; mean 1,989.86; SD 3,777.15) than unvaccinated women. Anti-nucleocapsid antibodies were present in women who developed COVID infection both in amniotic fluid and maternal blood but not in unvaccinated women. There was a high correlation between the concentrations of anti-spike antibody levels in serum and amniotic fluid of vaccinated women (p < 0.001; R = 1.0) and of anti-nucleocapsid antibody levels in serum and amniotic fluid of women who developed COVID infection (p < 0.001; R = 0.93). Conclusion: Recent studies have shown that SARS-CoV-2 vaccination during pregnancy is safe. Moreover, we can assume that there is an early transplacental antibody transfer after anti-SARS-CoV-2 immunization to protect the fetus, and there is also a high correlation between levels of anti-nucleocapsid antibodies in blood and amniotic fluid of pregnant women previously infected.

Case Report of An Extreme Premature Infant with Multisystem Inflammatory Syndrome in Neonates (MIS-N)

COVID-19 pandemic hit the world hard affecting more than 500 million people. In the SARS-CoV-2 pandemic era, there has been various information on the effect of COVID-19 infected or exposed pregnant women on their neonates. SARS-CoV-2 virus causes a hyperinflammatory syndrome in neonates similar to what may be seen in multisystem inflammatory syndrome in children (MIS-C) but due to transplacental transfer of antibodies rather than a neonatal infection with COVID-19. Case reports about a new pattern of disease, called multisystem inflammatory syndrome of neonate (MIS-N), have been recently appearing. We reviewed the perinatal history, clinical features, and outcomes of a preterm neonate with features consistent with MIS-N related to maternal SARS-CoV-2 infection that was managed in Texas, United States, in 2022. The infant presented with multisystem organ failure at 12 to 15 days of life. All extensive work up for infectious causes on the neonate were negative. Her inflammatory biomarkers were elevated, and she improved with steroids and supportive treatment. The neonate’s anti-SARS-CoV-2 IgG was positive and the IgM was negative. Though rare, we speculate that maternal SARS-CoV-2 and other autoantibodies crossing the placenta caused MIS-N. Further studies and reviews are needed to evaluate pathophysiology and to further evaluate the available treatments.

COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood.

Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and cross-neutralization capacity of maternal and cord antibody responses to SARS-CoV-2 variants following COVID-19 vaccination in pregnancy can inform neonatal immunity. Here we characterized the binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants. In addition, we evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. Our results reveal that the current COVID-19 vaccination induced significantly higher RBD-specific binding IgG titers in cord blood compared to maternal blood for both the Wuhan and Omicron BA1 strain. Interestingly, the binding IgG antibody levels for the Omicron BA1 strain were significantly lower when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, and BA4/5 specific neutralizing antibody levels were significantly lower compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not detected in either maternal or cord blood. Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for the Wuhan and Delta variants but not for the Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for bivalent boosters as new variants emerge.

DP17 A very rare presentation of linear IgA disease during pregnancy

Abstract We present a very rare immunobullous dermatosis, linear IgA disease (LAD), that developed during pregnancy, to highlight its clinical features, management and important safety considerations for the neonate. During her first pregnancy, a 32-year-old Japanese woman of 27 weeks’ gestation developed an intensely itchy blistering rash on her limbs, trunk and face without periumbilical predilection. The blisters were tense, clustering in an annular configuration, with subsequent development of blistering and erosions involving the oral and genital mucosae. Medications included a pregnancy multivitamin only. A lesional skin biopsy revealed a subepidermal blister containing neutrophils and eosinophils. Direct immunofluorescence of perilesional skin demonstrated linear deposition of IgA along the basement membrane zone. Linear IgA disease was diagnosed. Initial treatment consisted of erythromycin and daily clobetasol ointment. Owing to inadequate symptom control and blister progression, dapsone 50 mg daily was initiated with prompt improvement in her condition and cessation of new blistering. A postpartum flare necessitated a dose increase to 75 mg daily. Her baby’s glucose-6-phosphate dehydrogenase (G6PD) level was found to be normal at birth. She proceeded to breastfeed her son, and monitoring of his haemoglobin level was normal. Although her clinical presentation initially raised the possibility of pemphigoid gestationis (PG), there was no periumbilical involvement, and the morphology of blistering in conjunction with mucosal involvement was more suggestive of LAD. The immunofluorescence results also helped to distinguish LAD from PG. The new onset of LAD during pregnancy is very unusual and has been rarely reported (Ikkaku N, Tateishi N, Oda Y et al. Linear immunoglobulin A bullous dermatosis developing during late pregnancy. J Dermatol 2017; 44:e44–5). Pre-existing LAD typically improves during pregnancy, although postpartum flares are recognized. Pemphigoid gestationis has been associated with an increased risk of prematurity and intrauterine growth restriction, but this has not been reported with LAD during pregnancy, possibly due to its rarity. Both the diagnosis of LAD and its mainstay treatment—dapsone—have important potential implications for the neonate. As for other immunobullous diseases, transplacental transfer of pathogenic antibodies may result in transient, usually mild, neonatal blistering. Although dapsone can be safely used during pregnancy and breastfeeding, the risk of neonatal haemolysis and methemoglobinaemia necessitates the assessment of the G6PD level and haemoglobin monitoring in the neonate. Multidisciplinary input from the dermatology, obstetric and paediatric teams is crucial to ensure appropriate counselling and care of the affected mother and baby.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44–0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55–1.77 for IgG, 1.00–1.78 for live virus nAb and 1.79–2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

The non-specific effects of maternal immunization on birth outcomes: The evidence, mechanisms, and the implications.

Preterm birth (PTB) and stillbirth remain two of the most important causes of death, morbidity, and disability in childhood. Despite efforts to reduce PTB and stillbirth worldwide, rates of these adverse outcomes remain persistently elevated, independent of income setting. There is an urgent need for more effective interventions to reduce associated neonatal and early childhood morbidity and mortality. Maternal vaccines are a well-established strategy used for prevention of pathogen-specific disease in mothers and infants through transplacental antibody transfer. Beyond these pathogen-specific benefits, some studies have also identified non-specific effects (NSEs) of maternal vaccination protecting against several adverse birth outcomes, including PTB and stillbirth. This paper will review the evidence supporting the NSEs of maternal vaccination on birth outcomes, describe the possible underlying mechanisms, outline the research gaps, and summarize the significance from a global health perspective.