Influence of Distinct Maternal Cytomegalovirus-Specific Neutralizing and Fc Receptor-Binding Responses on Congenital Cytomegalovirus Transmission in HIV-Exposed Neonates.
Itzayana G Miller, Aakash Mahant Mahant, Jennifer A Jenks, Eleanor C Semmes, Eric Rochat, Savannah L Herbek, Caroline Andy, Nicole S Rodgers, Justin Pollara, Linda M Gerber, Betsy C Herold, Sallie R Permar
Author Information
Itzayana G Miller: Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA. ORCID
Aakash Mahant Mahant: Department of Microbiology-Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ORCID
Jennifer A Jenks: Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Eleanor C Semmes: Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Eric Rochat: Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Savannah L Herbek: Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Caroline Andy: Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10065, USA.
Nicole S Rodgers: Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Justin Pollara: Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Linda M Gerber: Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10065, USA. ORCID
Betsy C Herold: Department of Microbiology-Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ORCID
Sallie R Permar: Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
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 Fc��R1�� was higher in non-transmitting dyads, whereas HCMV-neutralizing antibody responses were higher in transmitting dyads. These findings suggest that engagement of Fc��R1�� 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.
