Nontyphoidal Salmonella (NTS) are important human enteric pathogens globally. Among the different serovars associated with human NTS disease, S . Newport (a serogroup C_{2}-C_{3} Salmonella ) accounts for a measurable proportion of cases. However, to date there are no licensed human NTS vaccines. NTS lipopolysaccharide-associated O polysaccharides are virulence factors and protective antigens in animal models. As isolated molecules, bacterial polysaccharides are generally poorly immunogenic, a limitation overcome by conjugation to a protein carrier. We report herein the development of a candidate serogroup C_{2}-C_{3} glycoconjugate vaccine based on S . Newport Core-O polysaccharide (COPS) and phase 1 flagellin (FliC). S . Newport COPS and FliC were purified from genetically engineered reagent strains, and conjugated at the polysaccharide reducing end to FliC protein lysines with thioether chemistry. S . Newport COPS:FliC immunization in mice improved anti-polysaccharide immune responses, generated high anti-FliC IgG titers, and mediated robust protection against challenge with both the homologous serovar as well another serogroup C_{2}-C_{3} serovar ( S . Muenchen). Analyses of S . Newport COPS:FliC induced sera found that the anti-COPS IgG antibodies were specific for serogroup C_{2}-C_{3} lipopolysaccharide, and could promote bactericidal killing by complement and uptake into phagocytes. These preclinical studies establish the protective capacity of serogroup C_{2}-C_{3} OPS glycoconjugates, and provide a path forward for the development of a multivalent Salmonella vaccine for humans that includes serogroup C_{2}-C_{3}.
【저자키워드】 Vaccine, flagellin, conjugate, Group C, O polysaccharide,