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

## TL;DR

This study explores how maternal antibodies against SARS-CoV-2 are transferred to infants and how vaccination improves the quality and breadth of these protective antibodies.

## Contribution

The study reveals that maternal vaccination leads to better functional antibody transfer to infants compared to natural infection.

## Key findings

- Cord blood antibodies from vaccinated mothers showed greater breadth and potency of effector functions compared to those from infected mothers.
- Antibody transfer efficiency is influenced by IgG subclass, affinity for antigen, and Fc receptor interactions.
- Vaccination enhances the functional breadth of inherited antibodies, potentially offering better infant protection against evolving SARS-CoV-2 variants.

## 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 from cord blood. Relevant to the continued protection of vulnerable infants in the context of a diversifying pathogen, key observations included the greater breadth of antibody effector functions as compared to neutralization, which was associated with greater affinity for antigen and the more efficient placental transfer of IgG subclasses with better affinity to Fc receptors. This work provides new insights into the binding and functional breadth of inherited antibody responses that are likely responsible for the protection of infants born to seropositive mothers from severe SARS-CoV-2 infection despite continued viral diversification.

This study addresses the passive transfer and inter-generational inheritance of functionally potent antibodies, and the relative ability of IgG antibodies to drive broad recognition and effector activities that may contribute to protection from COVID-19. While SARS-CoV-2-specific neutralizing activity was typically lost and antibody binding breadth and effector function were typically reduced in cord as compared to maternal blood, effector functions were substantially greater and broader following maternal vaccination than infection in both mothers and infants. The biases in levels, isotypes, subclasses, affinity for antigen, neutralization and effector function breadth and potency that associate with antigen exposure history have implications for protecting diverse populations from ever-diversifying viral variants.