CMV+ milk: morbidity risk & translational potential of neutralizing antibodies

PROJECT SUMMARY/ABSTRACT Over one-half the population of childbearing age women are cytomegalovirus (CMV) seropositive. More than 90% of CMV-seropositive women will shed the virus in their breast milk during the first month of lactation without clinical signs of systemic infection. Postnatal cytomegalovirus (pCMV) infection occurs in 4-20% of preterm infants, manifesting as a sepsis-like syndrome and respiratory decomposition. Developing novel strategies to eliminate the risk of pCMV infection or adverse host responses to CMV+ human milk in preterm infants is a critical step to maximize the safety of human milk delivery. The overall objectives of this study are to (1) test the potential of an added CMV neutralizing antibody to minimize cellular infiltration and infection, and to (2) characterize the human milk compositional differences in CMV+ versus CMV- milk and its impact on preterm health outcomes. We will conduct two complimentary specific aims: (1) Evaluate the pharmacokinetics and neutralizing efficacy of an anti-CMV antibody added to CMV+ milk. (2) Investigate the impact of mammary CMV reactivation on the human milk lipidome and determine the impact of receiving CMV+ human milk on neonatal outcomes. This proposal brings together leading experts in neonatology, neonatal nutrition, human milk lipidomics, infectious disease, CMV, and vaccine development. Adding anti-CMV neutralizing antibodies in CMV+ human milk has the potential to reduce the risk of postnatal CMV transmission in preterm infants who rely on breast milk for optimal nutrition. In addition, human milk compositional changes will be identified that will identify targets to mitigate the risk of lipidomic and inflammatory driven secondary disease outcomes related to CMV reactivation in breast milk and serve as efficacy biomarkers for future intervention trials to interrupt human milk CMV reactivation and infectivity.