Multiepitopic B- and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine

We have attempted to develop an anti-human immunodeficiency virus (HIV) lip opeptide vaccine with several HIV-specific long peptides modified by C-term inal addition of a single palmitoyl chain. A mixture of six lipopeptides de rived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) was prepared. A phase I study was conducted to evaluate immunogenicity and tole rance in lipopeptide vaccination of HIV-1-seronegative volunteers given thr ee injections of either 100, 250, or 500 mu g of each lipopeptide, with or without immunoadjuvant (QS21). This report analyzes in detail B- and T-cell responses induced by vaccination. The lipopeptide vaccine elicited strong and multiepitopic B- and T-cell responses. Vaccinated subjects produced spe cific immunoglobulin G antibodies that recognized the Nef and Gag proteins. After the third injection, helper CD4+-T-cell responses as well as specifi c cytotoxic CD8+ T cells were also obtained. These CD8+ T cells were able t o recognize naturally processed viral proteins. Finally, specific gamma int erferon-secreting CD8+ T cells were also detected ex vivo.