title: NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.
abstract: We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+)  and CD8(+)  T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.
authors.affiliation: Division of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Virginie
authors.initials: V
authors.lastname: Rozot
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Felicitas
authors.initials: F
authors.lastname: Bellutti Enders
authors.forename: Selena
authors.initials: S
authors.lastname: Vigano
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Tapia
authors.forename: Erika
authors.initials: E
authors.lastname: Castro
authors.forename: Séverine
authors.initials: S
authors.lastname: Burnet
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.forename: Daniel
authors.initials: D
authors.lastname: Garin
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013557:Switzerland; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; C078787:NYVAC vaccine; D012367:RNA, Viral; D014765:Viral Vaccines; D007371:Interferon-gamma