PIMELAUTIDE OR TRIMEXAUTIDE AS BUILT-IN ADJUVANTS ASSOCIATED WITH AN HIV-1-DERIVED PEPTIDE - SYNTHESIS AND IN-VIVO INDUCTION OF ANTIBODY AND VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTE-MEDIATED RESPONSE

Covalent association of lipopeptidic immunostimulants is known to impr ove the immunogenicity of short peptides. In this paper, we describe t he synthesis of four analytically pure immunogens, prepared by two dif ferent strategies, in which a hexadecameric peptide (V3) derived from the principal neutralizing domain of HIV-1 envelope glycoprotein was a ssociated with two different murein-derived lauroyl-peptides, Pimelaut ide (RP 44102), or Trimexautide (RP 56142). The in vivo immunogenicity of these compounds was evaluated according to two different criteria: the ability to elicit a cellular-T cytotoxic (CTL response) and the a bility to stimulate antibody response. Our studies shaw that one of ou r compounds (TrxSucV3) was able to efficiently induce a relevant virus -specific CTL response, while another one (PimSucV3) was able to stimu late a strong antibody response to the linked peptide, or to a co-inje cted protein. These results suggest that both activities rely on diffe rent structure-activity relationships and that such a chemically defin ed model of peptide vaccines may be used to selectively stimulate subp opulations of immunocompetent cells.