Non-typhoidal Salmonella (NTS) are a leading cause of pediatric invasive bacterial infections in sub-Saharan Africa with high associated case fatality rates in children under 5 years old. We have developed glycoconjugate vaccines consisting of the lipid A-removed surface polysaccharide of NTS, core and O-polysaccharide (COPS), and the flagellar monomer protein (FliC) from the homologous serovar as the carrier. We previously established that COPS:FliC was immunogenic and protective in mice immunized as adults or infants; however, the brief period of murine infancy precluded the evaluation of protection against invasive NTS (iNTS) disease in early life. In the present study, we used a mouse model of maternal immunization to investigate transmission of S . Typhimurium COPS:FliC-induced maternal antibodies and protection against lethal iNTS challenge in infant mice. We found that vaccinated dams developed high levels of COPS- and FliC-specific IgG, which were transferred to their offspring. Sera from both vaccinated mothers and their litters mediated complement-dependent bactericidal activity in-vitro . Passively immunized 2-week old infant mice born to vaccinated mothers were fully protected from challenge with an S . Typhimurium blood isolate from sub-Saharan Africa. The pre-clinical findings reported herein demonstrate that anti-COPS:FliC antibodies induced by vaccination are sufficient for protection of murine infants against experimental S . Typhimurium infection. By underscoring the protective role of antibody, our results suggest that maintaining an adequate titer of protective anti- Salmonella antibodies during early life, either through pediatric or maternal COPS:FliC vaccination, may reduce iNTS disease in young children in sub-Saharan Africa.
【저자키워드】 Vaccine, antibody, Infant, polysaccharide, Salmonella, flagellin, glycoconjugate, maternal transfer,