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

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 mu g/lipopeptide (N = 32), 150 mu g/lipopeptide (N = 32), 500 mu g/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 <= 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 mu g 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. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins