Immunization with the New Conjugate Vaccine against Salmonella Typhi Vi-CRM197 Induces Vi Specific Mucosal and Systemic Immune Responses in Mice

Typhoid fever is still a serious public health problem in the world, especially among young children. In the present work we asses the immunogenicity of the glycoconjugate vaccine Vi-CRM197, composed by the polysaccharide Vi antigen covalently coupled with the non toxic mutant of diphtheria toxin CRM197. Antibody and cellular responses, both local and systemic, were assessed upon subcutaneous injection of Vi-CRM197. The glycoconjugate elicited Vi-specific serum antibodies significantly higher than the polysaccharide Vi alone. A serum IgG isotype switching, with a prevalence of IgG1, was induced upon boosting and serum Vi-specific antibodies persisted up to 60 days after immunization. Interestingly, Vi-specific IgG, but not IgA, were present also in intestinal washes up to 60 days upon immunization. Splenocytes proliferation was observed after in vitro restimulation with Vi-CRM197. Moreover, lymphocytes collected from mesenteric lymph nodes, draining the intestinal tract, proliferated and produced IFN-γ upon restimulation with Vi-CRM197. These data confirm the immunogenicity of the glycoconjugate Vi-CRM197 and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM197 as promising candidate vaccine against S. Typhi.