title: Peptide immunogens based on the envelope region of HIV-1 are recognized by HIV/AIDS patient polyclonal antibodies and induce strong humoral immune responses in mice and rabbits.
abstract: Peptide immunogens produced by novel synthesis techniques and based on envelope proteins have repeatedly proven successful in inducing anti-HIV and anti-SIV responses in addition to producing anti-peptide immunity [Vaccine 12 (8) (1994) 736; AIDS Res. Hum. Retroviruses 14 (9) (1998) 751; Vaccine (2002) 2680]. We report here the design and evaluation of synthetic peptide constructs mimicking the variability of the third variable (V3) loop, or representing the conservation of the CD4 region of HIV-1 envelope. Three peptides based on the V3 region of HIV-1 subtype C gp120 and designated multiple epitope immunogens (MEI) differ in that one was randomly branched containing a spacer (b-MEI-s), another conjugated to a tetrameric lysine core (MEIV3b(4)) and the third conjugated to poly-L-lysine (poly-L-MEI). The method of synthesis employed produced peptides that were either linear, dimeric or tetramerically branched thereby providing differing levels of conformation. In addition the peptides also differed in their levels of variability. A fourth peptide designated B138 was based on a conserved region of HIV-1 envelope. The aim of this work was to evaluate the effect of variability and level of conformation on the immunogenicity of variable region peptides (MEI's) when compared to that of a known immunogenic and conserved region peptide (B138). Anti-peptide humoral immunity induced in BALB/c mice and New Zealand White rabbits produced antigen-recognizing antibody titres of </=5000 in enzyme linked immunosorbent assays (ELISA) and stimulation indices (SI) of 7 in cell proliferation assays. Plasma polyclonal antibodies collected from HIV/AIDS patients (from South Africa, Botswana and Puerto Rico) recognized the peptide constructs at antibody titres of </=5000. As demonstrated by mouse, rabbit and human antibody and proliferation responses, the immunogenicity and antigenicity of the peptides varied, with MEIV3b(4) responding better than the other three, at times even surpassing the conserved region peptide B138.
authors.affiliation: Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland Park 2006, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Hewer
authors.forename: D
authors.initials: D
authors.lastname: Meyer
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000276:immunology*; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D010455:Peptides; D014759:Viral Envelope Proteins