DNA/NYVAC Vaccine Regimen Induces HIV-Specific CD4 and CD8 T-Cell Responses in Intestinal Mucosa

Author:

Perreau Matthieu1,Welles Hugh C.1,Harari Alexandre12,Hall Olivia1,Martin Ricardo1,Maillard Michel3,Dorta Gian3,Bart Pierre-Alexandre1,Kremer Eric J.45,Tartaglia Jim6,Wagner Ralf7,Esteban Mariano8,Levy Yves91011,Pantaleo Giuseppe12

Affiliation:

1. Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland

2. Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland

3. Division of Gastroenterology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland

4. Institut de Génétique Moléculaire de Montpellier, CNRS 5535, Montpellier, France

5. Université Montpellier I & II, Montpellier, France

6. Sanofi Pasteur, Swiftwater, Pennsylvania

7. Institute of Medical Microbiology, University of Regensburg, Regensburg, Germany

8. Department of Molecular and Cellular Biology, National Center of Biotechnology (CNB-CSIC), Campus de Cantoblanco, Darwin 3, 28049 Madrid, Spain

9. Institut National de la Santé et de la Recherche Médicale, Unité U955, 94010 Créteil, France

10. Université Paris 12, Faculté de Médecine, 94010 Créteil, France

11. Assistance Public-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, 94010 Créteil, France

Abstract

ABSTRACT 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 α4β7 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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