TY - JOUR AU - Nelson, Cody S. AU - Cruz, Diana Vera AU - Tran, Dollnovan AU - Bialas, Kristy M. AU - Stamper, Lisa AU - Wu, Huali AU - Gilbert, Margaret AU - Blair, Robert AU - Alvarez, Xavier AU - Itell, Hannah AU - Chen, Meng AU - Deshpande, Ashlesha AU - Chiuppesi, Flavia AU - Wussow, Felix AU - Diamond, Don J. AU - Vandergrift, Nathan AU - Walter, Mark R. AU - Barry, Peter A. AU - Cohen-Wolkowiez, Michael AU - Koelle, Katia AU - Kaur, Amitinder AU - Permar, Sallie R. T1 - Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys PY - 2017/07/06/ AB - Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission in the setting of primary maternal infection and subsequent viremia, which is required for placental virus exposure. Pregnant, CD4+ T cell–depleted, rhesus CMV–seronegative (RhCMV-seronegative) rhesus monkeys were treated with either standardly produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV mixture. HIG passive infusion provided complete protection against fetal loss in both groups. The dose-optimized, RhCMV-neutralizing HIG additionally inhibited placental transmission of RhCMV and reduced viral replication and diversity. Our findings suggest that the presence of durable and potently neutralizing antibodies at the time of primary infection can prevent transmission of systemically replicating maternal RhCMV to the developing fetus, and therefore should be a primary target of vaccines to eliminate this neonatal infection. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.94002 VL - 2 IS - 13 UR - https://doi.org/10.1172/jci.insight.94002 PB - The American Society for Clinical Investigation ER -