PROJECT SUMMARY Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea, that continues to be associated with significant morbidity, mortality and stunting, among children <5 years of age living in low and middle income countries (LMIC). Although many ETEC vaccines are in clinical trials, none are currently licensed. To avoid further morbidity and mortality due to ETEC, an efficacious vaccine given effectively is urgently required. While the logical target group for ETEC vaccine would be infants, children in LMICs have been difficult to effectively immunize with other oral vaccines. To address this critical problem of low oral vaccine immune responses among infants in LMICs, an alternative strategy for protecting infants against ETEC needs to be explored. We hypothesize that maternal immunity may contribute to protecting infants from ETEC. However, the protective benefits and the components of maternal immunity associated with protection in infants from enteric infections like ETEC has not been widely studied. Therefore, if this route of passive immunity is feasible for ETEC is uncertain. Our aim is to study natural infections of ETEC in the mothers and babies to determine if the maternal antibodies to ETEC could prevent ETEC infections in children. We will also identify the ETEC antigens that are immunogenic and whose humoral immunity is transferable and protective to the neonates. Our specific hypothesis is that the antibodies to ETEC heat labile toxins, colonization factors and specific novel antigens transferred through breast milk would protect the infants from ETEC diarrhea and asymptomatic infections. ETEC-antibodies in the cord blood may also contribute to this protection. This passive protection may be enhanced by the bioactive factors like cytokines in the breastmilk and cord blood. To address our aims, we will enroll pregnant mothers and newborn dyads and follow them for two years of the child's age in Lima, Peru. This study will uncover the possibility of a more effective immunization approach for protecting infants from ETEC infections in the first year of life and beyond.