Immunogenicity and safety of an HIV-1 lipopeptide vaccine in healthy adults: a phase 2 placebo-controlled ANRS trial

AIDS. 2010 Sep 10;24(14):2211-23. doi: 10.1097/QAD.0b013e32833ce566.

Abstract

Background: French National Agency for Research on AIDS and Viral Hepatitis's HIV-LIPO-5 vaccine includes five HIV-1 peptides, containing multiple CD8 and CD4 T-cell epitopes and coupled to a palmitoyl tail. Whether HIV-LIPO-5 immunogenicity varies with the dose is unknown.

Methods: HIV-negative volunteers were randomized to receive HIV-LIPO-5 vaccine at 50 microg/lipopeptide (N = 32), 150 microg/lipopeptide (N = 32), 500 microg/lipopeptide (N = 33) or placebo (N = 34) at weeks 0, 4, 12 and 24. HIV-1-specific CD8 (interferon-gamma ELISpot on peripheral blood mononuclear cells cultured for 12 days) and CD4 responses (peripheral blood mononuclear cell lymphoproliferation) were assessed at baseline, after each injection and at week 48.

Results: Local reactions were dose-dependent but no differences in systemic reactions appeared between groups. Sustained (at least on two separate occasions) CD8 response rates to at least one given HIV-1 pool were obtained in 22 of 32 (69%), 21 of 33 (64%) and 21 of 34 (62%) individuals for LIPO-5 50, 150 and 500 groups, respectively (P < or = 0.0001 for all comparisons to the placebo). Cumulative CD4 response rates were obtained in 15 of 32 (47%), 18 of 33 (55%) and 15 of 34 (44%) individuals (P < 0.0001 for all comparisons to placebo). At week 48, CD8 responses persisted in 47 of 91 (52%) HIV-LIPO-5 recipients.

Conclusion: Doses of 50, 150 and 500 microg of French National Agency for Research on AIDS and Viral Hepatitis's HIV-LIPO-5 vaccine were able to elicit HIV-specific sustained CD8 and CD4 T-cell responses in healthy adults. Safety is good and all doses appear appropriate in further 'prime-boost' trials.

Trial registration: ClinicalTrials.gov NCT00121758.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Double-Blind Method
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular / immunology*
  • Injections, Intramuscular
  • Interferon-gamma
  • Lipopeptides / drug effects
  • Lipopeptides / immunology
  • Male
  • Middle Aged

Substances

  • AIDS Vaccines
  • Lipopeptides
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00121758