NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients

Eur J Immunol. 2012 Nov;42(11):3038-48. doi: 10.1002/eji.201242696. Epub 2012 Oct 1.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HIV / immunology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / therapy*
  • HIV Infections / virology
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Switzerland
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / immunology

Substances

  • Anti-HIV Agents
  • NYVAC vaccine
  • RNA, Viral
  • Viral Vaccines
  • Interferon-gamma