Maternal immune correlates of protection against placental transmission of cytomegalovirus

Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. In a subset of infected infants, congenital HCMV causes severe, long-lasting sequelae, including deafness, microcephaly, neurodevelopmental delay, and even death. Accordingly, a maternal vaccine to prevent congenital HCMV infection continues to be a top public health priority. Nevertheless, all vaccines tested to date have failed to meet clinical trial endpoints. Maternal immunity provides partial protection against congenital HCMV transmission, as vertical transmission from seropositive mothers is relatively rare. Therefore, an understanding of the maternal immune correlates of protection against HCMV congenital infection will be critical to inform design of an efficacious maternal vaccine. This review summarizes our understanding of the innate and adaptive immune correlates of protection against congenital transmission of HCMV, and discusses the advantages and applications of a novel nonhuman primate model of congenital CMV transmission to aid in rational vaccine design and evaluation.