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 improve the immunogenicity of short peptides. In this paper, we describe the synthesis of four analytically pure immunogens, prepared by two different strategies, in which a hexadecameric peptide (V3) derived from the principal neutralizing domain of HIV-1 envelope glycoprotein was associated with two different murein-derived lauroyl-peptides, Pimelautide (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 ability to stimulate antibody response. Our studies show that one of our compounds (TrxSucV3) was able to efficiently induce a relevant virus-specific CTL response, while another one (PimSucV3) was able to stimulate a strong antibody response to the linked peptide, or to a co-injected protein. These results suggest that both activities rely on different structure-activity relationships and that such a chemically defined model of peptide vaccines may be used to selectively stimulate subpopulations of immunocompetent cells.
Déprez
B
B
Faculté de Pharmacie, URA CNRS 1309, Institut Pasteur de Lille, France.
Gras-Masse
H
H
Martinon
F
F
Gomard
E
E
Lévy
J P
JP
Tartar
A
A
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010867:Pimelic Acids / Q000138:chemical synthesis* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D009842:Oligopeptides; D010446:Peptide Fragments; D010867:Pimelic Acids; C024768:trimexautide; C061086:pimelautide