ABSTRACT: Congenital cytomegalovirus (cCMV) infection is the most common placentally transmitted infection worldwide, causing long-lasting complications for affected children, including hearing loss, developmental delays, seizures, and even death. After 40+ years of research, there is no licensed vaccine against CMV, despite high prioritization in vaccine development. Little is currently known about the maternal immune responses that prevent transmission during pregnancy, which is vital information for developing effective vaccines and treatments for cCMV. Prior studies using our rhesus monkey model of placental CMV transmission have determined that the presence of pre-existing antibodies reduce peak maternal viral load and protect against placental transmission, yet the antibody functions that mediated this protection has not been defined. Moreover, our group has demonstrated that non-neutralizing antibody effector functions mediated the partial protection against CMV acquisition achieved in three CMV glycoprotein B vaccine trials. Thus, this study will assess antibody effector functions, including antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), as correlates of protection against in utero transmission of CMV in animals with and without pre-existing passive humoral immunity. Binding mediators of antibody effector functions, including Fc receptor binding and cell-associated antigen binding, will also be assessed. Additionally, we will characterize the maternal effector cell populations that mediate non-neutralizing effector functions to explore the role of these cell types in vertical CMV transmission. Considering the high global incidence of cCMV and associated neurologic impairment, developing an effective vaccine guided by established immune correlates to prevent cCMV is imperative to improving global pediatric health.