Rotaviruses and caliciviruses account for 10 to 50% of gastroenteritis episodes in children worldwide. This project will define further the relevant antibodies and glycoconjugates that protect infants from RV diarrhea with the overall goal of preventing infection and illness despite antigenic diversity. Recent breakthroughs in the molecular characterization of CVs have permitted development of new assays and genetic comparisons that have superseded previous diagnostic methods and classifications of CVs. The new assays have not been applied to longitudinal studies of closely monitored children and assessment of infection, correlates of protection, and non-immunoglobulin protective factors in such studies are likely to yield new information of seminal importance to our understanding of CVs. Our hypothesis is that antibody and non-antibody factors bind viral gastroenteritis pathogens and protect breast-fed infants from disease. The hypothesis will be addressed by the following specific aims: 1. To measure antibody levels in the cohort and associate those antibodies with protection against rotavirus and calicivirus infection and illness. 2. To examine non-antibody factors in human milk that are associated with protect against rotavirus and calicivirus infection and illness in the suckling. 3. To determine whether maternal immunization with rotavirus vaccine results in enhanced protection against rotavirus diarrhea in breast-fed infants. 4. To determine whether antibody to rotavirus non-structural protein 4 (NSP4), a potential viral enterotoxin, is a correlate of protection against rotavirus infection, and illness and whether human milk contains antibody or non-antibody factors that bind to NSP4. 5. To assess the immunomodulating effect of human milk on response to rotavirus vaccination.
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