Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model.

Cytomegalovirus (CMV) is the most common infectious cause of birth defects globally, but we still do not have licensed medical interventions to prevent vertical transmission of CMV. We utilized a non-human primate model of primary CMV infection during pregnancy to study virological and humoral factors that influence congenital infection. Unexpectedly, we found that the levels virus in maternal plasma were not predictive of virus transmission to the amniotic fluid (AF) in immunocompetent dams. In contrast, CD4+ T cell depleted pregnant rhesus macaques with virus detected in AF had higher plasma viral loads than dams not showing placental transmission. Virus-specific antibody binding, neutralizing, and Fc-mediated antibody effector antibody responses were not different in immunocompetent animals with and without virus detectable in AF, but passively infused neutralizing antibodies and antibodies binding to key glycoproteins were higher in CD4+ T cell-depleted dams who did not transmit the virus compared to those that did. Our data suggests that the natural development of virus-specific antibody responses is too slow to prevent congenital transmission following maternal infection, highlighting the need for the development of vaccines that confer levels of pre-existing immunity to CMV-naïve mothers that can prevent congenital transmission to their infants during pregnancy.