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Modified HGP-30 peptide heteroconjugate: novel approach in HIV vaccine development.

Zimmerman DH, Lloyd JP, Winship MD, Sarin PS; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 142 (abstract no. 422).

Cel-Sci Corporation, Alexandria, VA.

AIDS has become a global problem for which the development of a safe, stable and effective vaccine has become essential. HGP-30, a 30 amino acid synthetic peptide homologous to a highly conserved region of HIV-1 p17, has previously been shown to elicit both cellular and humoral immune responses when conjugated to KLH and used with alum as the adjuvant. The ability of a heteroconjugate consisting of a 15 amino acid segment of human beta-2-microglobulin (beta-2-M'), linked with a modified HGP-30 sequence (m-HGP-30) to induce IgG2a and IgG2b antibodies in BALB/c mice was studied. The effects of different adjuvants and doses of the immunogens were evaluated for serum antibody titers, specificity and isotypes. The adjuvants were Alum, Incomplete Freund's, Ribi (MPL and TDM) and Novasome (a nonphospholipid based liposome). The antigen doses used per inoculation were 1.6, 8 or 40 micrograms. The heteroconjugate (beta-2-M'-m-HGP-30) generated immune response better or comparable to other formulations as judged by: (1) Antibody titers induced by the heteroconjugate (beta-2-M'-m-HGP-30) were comparable to those induced by HGP-30-KLH; (2) Antigen specificity was better for heteroconjugate induced antisera than HGP-30-KLH and m-HGP-30-KLH induced antisera; (3) Both the heteroconjugate and m-HGP-30-KLH induced higher responses of antibody isotypes indicative of a TH1 pathway, notably IgG2a and IgG2b, compared to HGP-30-KLH; and (4) Response rates showed that Novasomes and Ribi (MPL and TDM) system were superior adjuvants to Incomplete Freund's and Alum. These results suggest the modified HGP-30 heteroconjugate, beta-2-M'-m-HGP-30, may be useful as an HIV vaccine for induction of TH1 antibodies and cell mediated immune responses.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Adjuvants, Immunologic
  • Alum Compounds
  • Animals
  • HIV Infections
  • HIV Seropositivity
  • Hemocyanin
  • Humans
  • Immune Sera
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Mice
  • Peptides
  • Vaccination
  • aluminum sulfate
  • beta 2-Microglobulin
  • keyhole-limpet hemocyanin
Other ID:
  • 97926160
UI: 102223169

From Meeting Abstracts




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