DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa

M. Perreau , H. C. Welles , A. Harari , O. Hall , R. Martin , M. Maillard , G. Dorta , P. A. Bart , E. J. Kremer (1) , J. Tartaglia , R. Wagner , M. Esteban , Y. Levy , G. Pantaleo

1 IGMM - Institut de Génétique Moléculaire de Montpellier

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed alpha4beta7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

Mots clés: AIDS Vaccines/administration & dosage/*immunology Adult Blood/immunology CD4-Positive T-Lymphocytes/*immunology CD8-Positive T-Lymphocytes/*immunology Humans Intestinal Mucosa/*immunology Middle Aged Smallpox Vaccine/administration & dosage/*immunology Vaccination/methods Vaccines; DNA/administration & dosage/*immunology Viral Vaccines/administration & dosage/*immunology

Domaines: Biochimie, Biologie Moléculaire

M. Perreau, H. C. Welles, A. Harari, O. Hall, R. Martin, et al.. DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa. Journal of Virology, 2011, 85 (19), pp.9854--62. ⟨10.1128/JVI.00788-11⟩. ⟨hal-02193496⟩