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

  • Carreño JM Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Perez-Shibayama C Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Gil-Cruz C Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Lopez-Macias C Medical Research Unit on Immunochemistry (UIMIQ), Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute (IMSS), Mexico City, Mexico.
  • Vernazza P Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Ludewig B Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Albrich WC Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
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  • 2017-06-02
Published in:
  • PloS one. - 2017
Administration, Oral
Antibodies, Bacterial
B-Lymphocytes
Bacterial Outer Membrane Proteins
Bacterial Vaccines
CD4-Positive T-Lymphocytes
Humans
Salmonella typhi
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/278284
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