SIMIAN IMMUNODEFICIENCY VIRUS AS A MODEL FOR VACCINATION AGAINST HIV - INDUCTION IN RHESUS MACAQUES OF GAG-SPECIFIC OR NEF-SPECIFIC CYTOTOXIC T-LYMPHOCYTES BY LIPOPEPTIDES

The protection against infection by HIV probably requires the inductio n of both neutralizing Abs and CTL responses. Vaccination by attenuate d HIV is hardly acceptable and the use of viral genes inserted in reco mbinant living vectors needs further development, especially with resp ect to safety. The peptidic vaccination is a promising approach but fr ee peptides are usually poorly immunogenic. Because potent immune resp onses have been obtained in mice with modified peptides such as lipope ptides, we have designed a study to assess the immunogenicity of lipop eptides in nonhuman primates. Seven lipopeptides were synthesized, der ived from known immunogenic regions of the simian immunodeficiency vir us (SIV) NEF and GAG proteins. Twelve rhesus macaques, randomly chosen and not selected on their MHC basis, were immunized subcutaneously wi th the seven lipopeptides in IFA. An MHC class I-restricted and CD8(+) -mediated CTL response has been observed in seven macaques directed ag ainst one or two of the synthetic immunizing peptides in each case. Th ese CTLs were able to lyse autologous target cells infected with a rec ombinant vaccinia virus expressing the SIV nef or gag genes, suggestin g that they recognized the naturally processed peptides. These activit ies are detectable in peripheral blood cells for at least 10 mo after the last immunization. Abs against the immunizing peptides have also b een observed in all cases. This study demonstrates that lipopeptides c an generate cytotoxic and humoral immune responses in a large number o f unselected animals and this approach may thus be worth considering i n the vaccination against HIV.