Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterized the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals, and evaluated transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses revealed lower vaccine-induced functions and Fc-receptor binding after Ad26.COV2.S compared to mRNA vaccination, and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccinees had higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination resulted in enhanced maternal immune responses relative to second trimester. Higher cord:maternal transfer ratios following first and second trimester vaccination reflect placental compensation for waning maternal titers. These results support vaccination early in pregnancy to maximize maternal protection throughout gestation, without compromising neonatal antibody protection.

Covid-19 Vaccination in Pregnancy: A Systematic Review

Objective: Pregnancy is a risk factor for severe Covid-19. Looking for safe vaccines that evoke protective maternal and fetal antibody response is important. Methods: We searched from registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021. Articles were selected based on inclusion and exclusion criteria after duplicates were removed. Infection rate, maternal antibody response, placental antibody transfer, and adverse events were described. This systematic review was performed with quality assessment and semi-quantitative synthesis according to PRISMA guidelines. Results: Twelve observational studies with a total of 40.509 pregnant women included. The mRNA based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infections (p=0.0004). Both vaccines did not affect pregnancy, delivery, and neonatal outcomes. The most commonly encountered adverse reactions are injection-site pain, fatigue, and headache but only transient. Antibody responses were rapid after the prime dose of vaccines. After booster, antibody responses were higher and associated with better placental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and better antibody transfer ratio. Conclusions: The Pfizer-BioNTech and Moderna vaccines are efficacious for preventing future SARS-CoV-2 infections. These vaccines can be considered as a safe option for pregnancy and their fetus. Two doses of vaccines were recommended for more robust maternal and fetal antibody responses. Longer latency was associated with higher fetal antibody responses.

Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

There is a persistent male bias in the prevalence and severity of COVID-19 disease. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of disease in adults, and play a key role in the placental anti-viral response. Moreover, the interferon response has been shown to alter Fc-receptor expression, and therefore may impact placental antibody transfer. Here we examined the intersection of viral-induced placental interferon responses, maternal-fetal antibody transfer, and fetal sex. Placental interferon stimulated genes (ISGs), Fc-receptor expression, and SARS-CoV-2 antibody transfer were interrogated in 68 pregnancies. Sexually dimorphic placental expression of ISGs, interleukin-10, and Fc receptors was observed following maternal SARS-CoV-2 infection, with upregulation in males. Reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were noted in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

mSphere of Influence: Learning from Nature—Antibody Profiles Important for Protection of Young Infants

ABSTRACT Esther Ndungo works in the field of maternal-infant immunity against enteric pathogens. In this mSphere of Influence article, she reflects on how the paper “Fc glycan-mediated regulation of placental antibody transfer” by Jennewein et al. (M. F. Jennewein, I. Goldfarb, S. Dolatshahi, C. Cosgrove, et al., Cell 178:202–215.e14, 2019, https://doi.org/10.1016/j.cell.2019.05.044) impressed upon her the value of thinking “outside the box” and looking to nature to guide her research.