Glycoconjugate vaccine strategies for protection against invasive Salmonella infections

Abstract

Salmonella enterica serovars Typhi and Paratyphi A and B and certain non-typhoidal Salmonella enterica (NTS) serovars are important causes of invasive Salmonella disease worldwide. NTS serovars Typhimurium and Enteritidis typically cause gastroenteritis in healthy children and adults in industrialized countries but in certain hosts (e.g., young infants, the elderly, immunocompromised individuals) they also cause invasive infections. These two serovars also cause invasive disease in infants and young children in sub-Saharan Africa. Whereas Salmonella surface polysaccharides are poor immunogens in animal models and do not generate immunologic memory, conjugation with carrier proteins overcomes these limitations. S. Typhi expresses a Vi polysaccharide capsule; Vi either alone or as a glycoconjugate protects humans from typhoid fever. In contrast, S. Paratyphi A and B and NTS (with rare exceptions) do not express capsular polysaccharides. Rather, their surface polysaccharides are the O polysaccharide (OPS) of lipopolysaccharide. In animal studies, immunization with Salmonella COPS (core polysaccharide-OPS) conjugated with carrier proteins generates functional immunity and protects against fatal Salmonella challenge. Conjugating to Salmonella proteins (flagellin, porins) may extend immune responses to another relevant target for antibody generation and enhance the glyconjugate’s efficacy.