Immunogenicity and efficacy following sequential parenterally-administered doses of Salmonella Enteritidis COPS:FliC glycoconjugates in infant and adult mice

摘要

Author summary Non-typhoidal Salmonella enterica (NTS) serovars Enteritidis and Typhimurium (including monophasic variant I 4,[5],12:i:-) are significant causes of invasive bacterial disease amongst infants and toddlers in sub-Saharan Africa, and currently, there are no approved NTS vaccines. We have demonstrated previously that immunization with S. Enteritidis core and O-polysaccharide (COPS) conjugated to the flagellin protein (FliC) from the homologous serovar protected adult mice from fatal infection with a Malian S. Enteritidis blood isolate. The target population for iNTS vaccines in sub-Saharan Africa, however, are young infants. In the current study, we evaluated S. Enteritidis COPS:FliC vaccination during murine infancy or adulthood. We found that COPS:FliC was immunogenic in both adult and infant mice and that co-formulation with adjuvant impacted the magnitude and quality of the immune response. Despite these differences, all vaccine formulations protected against experimental challenge in both age groups. Furthermore, robust efficacy was attainable after only two COPS:FliC doses, coinciding with the appearance of COPS-specific antibodies. The results from this study suggest that S. Enteritidis COPS:FliC is a promising pediatric vaccine candidate for use in sub-Saharan Africa and may help inform potential immunization strategies for iNTS COPS:FliC conjugate vaccines.