Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection. Academic Article uri icon

Overview

abstract

  • Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.

publication date

  • August 15, 2022

Research

keywords

  • Cytomegalovirus Infections
  • Cytomegalovirus Vaccines
  • Herpesviridae Infections

Identity

PubMed Central ID

  • PMC9374380

Scopus Document Identifier

  • 85136340128

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2019.05.046

PubMed ID

  • 35763348

Additional Document Info

volume

  • 132

issue

  • 16