Patterns and functional consequences of antibody speciation in maternal-fetal transfer of coronavirus-specific humoral immunity

Abstract

Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc domain glycosylation, antigen-specificity, and the temporal dynamics of maternal antibody responses. Here, we investigate the phenotypes and functions of maternal and cord blood antibodies induced by SARS-CoV-2 infection and compare them to those induced by mRNA vaccination, focusing on breadth of antigen recognition and antiviral functions including neutralization and effector function. While cord blood coronavirus-specific antibody functional breadth and potency appeared to be more compromised than binding breadth and potency in both groups, vaccination induced substantially greater function and breadth in cord blood than did natural infection. These functional phenotypes were associated with speciation of the maternal serum repertoires, as some IgG subpopulations were enriched while others were relatively depleted. Relevant to the continued protection of vulnerable populations in the context of a diversifying pathogen, greater breadth was observed for antibody effector functions than for neutralization, and these activities were associated with greater affinity for antigen. This work provides insights into the functional breadth of maternal-fetal antibody responses in the context of novel mRNA vaccines and a recently emerged pathogen that is likely to be a public health burden for the foreseeable future.