116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition

Abstract

BackgroundCongenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, including the role of CMV-specific IgG. Defining the role of passively acquired maternal IgG in the protection of half of the CMV-exposed, breastfeeding infants against postnatal CMV acquisition may inform CMV vaccine designMethodsWe analyzed CMV-specific humoral responses in 29 CMV-seropositive Ugandan mother–infant pairs. Seventeen mothers were HIV co-infected. Infants were followed weekly for postnatal CMV acquisition using saliva PCR. Twelve infants acquired CMV and 17 infants did not acquire CMV in the first 6 months of life. We compared CMV-specific IgG responses at delivery of mothers whose infants acquired CMV to mothers whose infants did not acquire CMV by 6 months of life and in the infants at 6 weeks of life. We also compared CMV-specific responses in mothers at delivery and infants at 6 weeks of life based on maternal HIV status.ResultsWe found similar CMV-specific total IgG and IgG3 binding, avidity index, neutralization, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity responses in mothers whose infants did or did not acquire CMV by 6 months of life. Moreover, similar CMV-specific IgG binding and neutralization responses were also found between infants who did or did not acquire CMV by 6 months of life. Finally, CMV-specific IgG responses were similar in HIV-infected and uninfected mothers at delivery and in infants at 6 weeks of life regardless of perinatal HIV exposure.ConclusionCMV-binding and functional IgG responses do not appear to impact infant susceptibility to postnatal CMV acquisition in the first 6 months of life, and therefore other viral or immunologic factors contribute to the inefficiency of this mode of CMV transmission. Thus, to provide sterilizing protection against mucosal CMV acquisition, an antibody-based CMV vaccine would likely have to induce higher magnitude or qualitatively different responses than that of natural infection.Disclosures All authors: No reported disclosures.