Maternal:fetal functional antibody transfer for protection against SARS-CoV-2

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), has posed a serious global health threat since its emergence in late 2019, resulting in millions of infections across the world. Specifically, pregnant individuals and their infants are particularly at risk for severe COVID-19. A lack of inclusion of these populations in vaccine trials has limited our ability to optimize protection through humoral immunity. The emergence of SARS-CoV-2 offered an unprecedented opportunity to characterize maternal transfer of antibodies to neonates in response to both infection and vaccination with a novel pathogen. Using an unbiased, comprehensive antibody profiling approach, this work explores the correlates of protection against SARS-CoV-2 to understand the antibody qualities that are crucial for maternal:fetal antibody transfer. We found that third trimester infection drove inefficient antibody transfer through the placenta and resulted in a limited titer of inflammatory antibodies in breastmilk. Although vaccination in pregnancy and lactation induced less inflammatory antibodies than in nonpregnant women, boosting during pregnancy induced comparable antibody immunity to nonpregnant populations. Subtle differences were observed between vaccine platforms and trimester of vaccination in both the induction of vaccine-induced immunity in pregnant populations and in the transfer of antibodies to the neonate. These data provide novel insights for further optimization of maternal immunization strategies and increase our understanding of the transfer of humoral defenses at the maternal:fetal barrier.