Immunization with the conjugate vaccine Vi-CRM(197) against Salmonella Typhi induces Vi-specific mucosal and systemic immune responses in mice

Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM(197), composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM(197), is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM(197). The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM(197) was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM(197) and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM(197) as a promising candidate vaccine against Salmonella Typhi.