# Influence of Distinct Maternal Cytomegalovirus-Specific Neutralizing and Fc Receptor-Binding Responses on Congenital Cytomegalovirus Transmission in HIV-Exposed Neonates

## TL;DR

This study explores how maternal immune responses to cytomegalovirus affect the risk of passing the virus to newborns, especially in mothers with HIV.

## Contribution

The study identifies specific maternal antibody functions associated with protection or risk of congenital CMV transmission in HIV/HCMV co-infected women.

## Key findings

- Higher HCMV-specific IgG binding to FcγR1α was observed in non-transmitting mother-infant pairs.
- Higher HCMV-neutralizing antibody responses were found in transmitting dyads.
- The findings highlight the importance of validating immune correlates in diverse HIV/HCMV co-infected populations.

## Abstract

Congenital cytomegalovirus (cCMV) is the most common infectious cause of birth defects worldwide, affecting approximately 1 in every 200 live-born infants globally. Recent work has identified potential immune correlates of protection against cCMV transmission including maternal and placentally transferred antibody levels and their function, which may inform the development of maternal active (vaccine) and passive (mono/polyclonal antibody) immunizations. However, these correlates need to also be assessed in diverse cohorts, including women living with HIV who have increased risk of cCMV transmission. Using a case–control design, we investigated whether the magnitude, specificity, function and placental transfer of maternal IgG responses are associated with protection against and/or risk of cCMV transmission in HIV/HCMV co-infection. Within 3 historical cohorts of pregnant women with HIV/HCMV co-infection, we identified 16 cCMV transmitting cases that were matched to 29 cCMV non-transmitting controls. Using a systems serology approach, we found that normalized HCMV-specific IgG binding to FcγR1α was higher in non-transmitting dyads, whereas HCMV-neutralizing antibody responses were higher in transmitting dyads. These findings suggest that engagement of FcγR1α by HCMV-specific IgG may help confer protection against cCMV transmission. Building upon previous research, our study reinforces the critical role of validating maternal humoral immune correlates of cCMV transmission risk across diverse seropositive cohorts, providing essential insights to inform and accelerate the development of effective HCMV vaccines.