Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers

Vaccine. 2007 Jan 5;25(3):510-8. doi: 10.1016/j.vaccine.2006.07.050. Epub 2006 Aug 10.

Abstract

Background: Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system.

Methods: Eighty-four HIV uninfected human participants were vaccinated intramuscularly at 0, 1, and 3 months and evaluated for safety. Immune responses were analyzed for the presence of vaccine-induced antibody and T lymphocyte responses.

Results: The vaccines were safe and well tolerated at all doses. Nef-, Tat-, and gp120-specific binding antibodies were induced in all individuals that received the respective antigen, lasting up to 9 months after the final immunization. Antibodies able to neutralize the T-cell laboratory-adapted strain of HIV-1(W61D) were detected in the majority of vacinees, but did not neutralize primary isolates. Envelope-specific antibody-dependent cell cytoxicity was detected in most of the individuals receiving gp120. Robust and persistent HIV-specific lymphoproliferative responses were detected against all subunit proteins in the majority of immunized participants. As expected, HIV-specific CD8 T-cell responses were not detected.

Conclusions: Despite the lack of primary isolate neutralizing antibody induction, the observed high frequency and magnitude of other immune responses warrant further work with this vaccine or vaccine components.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic / pharmacology*
  • Adolescent
  • Adult
  • Antibody Formation / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Antibodies / adverse effects
  • HIV Antibodies / biosynthesis*
  • HIV Envelope Protein gp120 / immunology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular / immunology
  • Interferon-gamma / analysis
  • Malaria Vaccines / pharmacology
  • Male
  • Middle Aged
  • Neutralization Tests
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / immunology

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Malaria Vaccines
  • RTS,S-AS02A vaccine
  • Vaccines, Synthetic
  • Interferon-gamma