Immunogenicity and Protective Efficacy Against C-C Infection in Mice Immunized with a Glycoconjugate of Newport Core-O Polysaccharide Linked to the Homologous Serovar FliC Protein

Nontyphoidal (NTS) are important human enteric pathogens globally. Among the different serovars associated with human NTS disease, . Newport (a serogroup C-C) 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-C glycoconjugate vaccine based on . Newport Core-O polysaccharide (COPS) and phase 1 flagellin (FliC). . 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. . 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-C serovar (. Muenchen). Analyses of . Newport COPS:FliC induced sera found that the anti-COPS IgG antibodies were specific for serogroup C-C lipopolysaccharide, and could promote bactericidal killing by complement and uptake into phagocytes. These preclinical studies establish the protective capacity of serogroup C-C OPS glycoconjugates, and provide a path forward for the development of a multivalent vaccine for humans that includes serogroup C-C.