Lipopeptides induce cell-mediated anti-HIV immune responses in seronegative volunteers

Objective: Test the efficacy of a mixture of six NEF (N1, N2, N3), GAG (G1, G2) and ENV (E) lipopeptides in the induction of B- and T-cell anti-HIV re sponses. Design: A randomized phase 1 open-label dose-finding trial. Twenty-eight he althy seronegative volunteers received the lipopeptides, with or without th e adjuvant QS(21). Methods: Anti-HIV-peptide antibodies were detected by enzyme-linked immunos orbent assay and Western blotting. Induction of cellulary responses was ass essed by proliferative test and Cr-51-release assay. Results: Local and systemic adverse reactions were always mild or moderate. After three injections an antibody response was detected in 25 out of 28 v olunteers (89%). T cells from 19 (79%) of the 24 volunteers proliferated in response to at least one peptide. The majority of the volunteers had induc ed a multispecific proliferative response; that is, cells from volunteers p roliferated to two (five of 19), three (five of 19), four (three of 19) or five peptides (one of 19). Cytotoxic responses by anti-HIV CD8+ lymphocytes could be tested in 24 volunteers, 13 (54%) of whom had clear and reproduci ble responses, with strong activity in the remaining 12 (> 20% of specific lysis), and polyepitopic responses were detected in at least seven of the 1 3 responders. Cytotoxic responses were found against the whole NEF protein (clade B LAI) in three of four tested volunteers and cross-reactions with t he proteins of clade B (MN) and clade A (Bangui) HIV-1 strains, and also HI V-2 ROD, were detected in one of two tested volunteers. Conclusions: Lipopeptides are promising immunogens for an AIDS vaccine. (C) 2001 Lippincott Williams & Wilkins.