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Vaccination against complex pathogens such as typhoidal and non-typhoidal  Salmonella  requires the concerted action of different immune effector mechanisms. Outer membrane proteins (Omps) of  Salmonella  Typhi are potent immunogens, which elicit long-lasting and protective immunity. Here, we followed the evolution of  S . Typhi OmpC and F-specific T and B cell responses in healthy volunteers after vaccination with the vaccine strain Ty21a. To follow humoral and cellular immune responses, pre- and post-vaccination samples (PBMC, serum and stool) collected from 15 vaccinated and 5 non-vaccinated individuals. Immunoglobulin levels were assessed in peripheral blood by enzyme-linked immunosorbent assay. B cell and T cell activation were analyzed by flow cytometry. We observed a significant increase of circulating antibody-secreting cells and maximal Omp-specific serum IgG titers at day 25 post vaccination, while IgA titers in stool peaked at day 60. Likewise, Omp-specific CD4 +  T cells in peripheral blood showed the highest expansion at day 60 post vaccination, concomitant with a significant increase in IFN-γ and TNFα production. These results indicate that  S . Typhi Omp-specific B cell responses and polyfunctional CD4 +  T cell responses evolve over a period of at least two months after application of the live attenuated vaccine. Moreover, these findings underscore the potential of  S . Typhi Omps as subunit vaccine components.   Trial registration:   ISRCTN18360696

plos one

Evolution of Salmonella Typhi outer membrane protein-specific T and B cell responses in humans following oral Ty21a vaccination: A randomized clinical trial