Nontyphoidal Salmonella (NTS) are major human gastrointestinal pathogens worldwide. S. Newport (a serogroup C2-C3 Salmonella) accounts for a significant number of cases among the many serovars linked with human NTS illness. However, there are currently no approved human NTS vaccinations. In animal models, NTS lipopolysaccharide-associated O polysaccharides function as virulence agents and protective antigens. Bacterial polysaccharides are typically immunogenic as separate molecules, a disadvantage that is addressed by conjugation to a protein carrier. The development of a potential serogroup C2-C3 glycoconjugate vaccine based on S. Phase 1 flagellin and Newport Core-O polysaccharide (COPS) (FliC). S. Newport COPS:FliC vaccination enhanced anti-polysaccharide immune responses, produced high anti-FliC IgG titers, and provided strong protection against challenge with both the homologous and another serogroup C2-C3 serovar (S. Muenchen). 

Anti-COPS IgG antibodies identified in S. Newport COPS:FliC generated sera were selective for serogroup C2-C3 lipopolysaccharide and may enhance bactericidal killing via complement and absorption into phagocytes. These preclinical experiments demonstrate the protective potential of serogroup C2-C3 OPS glycoconjugates and pave the way for the creation of a multivalent Salmonella vaccine for humans containing serogroup C2-C3.