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7th International AIDS ConferenceFlorence, Italy — June 16-21, 1991 |
Int Conf AIDS 1991 Jun 16-21; 7:39 (abstract no. M.A.68)
Charles S, Matthews T, Chong P, Haynes J, Rovinski B, Cao SX, Bolognesi D, Klein M; Connaught Centre for Biotechnology Research, 1755 Steeles Avenue West, Willowdale, Ont. M2R 3T4, Canada
OBJECTIVE: To construct synthetic HIV vaccine candidates using defined T- and B-cell epitopes of HIV structural proteins.
METHODS: Chimeric oligopeptides containing either a gp120 or a gp41 B-cell epitope from the MN and LAV isolates, respectively, linked in tandem to either the N- or C-terminus of a defined p24 T-cell epitope, p24E (residues 292-306) were synthesized. Immunogenicity studies of the synthetic constructs were tested in inbred mice to determine the ability of the T-cell epitope to mediate anti-envelope antibody responses against the individual B-cell epitopes. Anti-B-cell epitope antibody levels were measured by peptide-specific Enzyme Immunoassays, and the functional properties of the antibodies assessed by "in vitro" neutralization and syncytia formation inhibition assays.
RESULTS: The immunogenicity of the major neutralizing epitope (V3 loop, residues 311-327) was higher when the peptide was linked to the C-rather than the N-terminus of p24E, whereas the B-cell epitope, BE3 (residues 721-751), required to be strictly linked to the C-terminus of the T-cell epitope to elicit an anti-BE3 antibody response. Only the antiserum raised against the p24E-V3 but not V3-p24E construct was found to manifest potent neutralizing and syncytia inhibition activities against the homologous (MN) virus.
CONCLUSIONS: Epitope-polarity critically influences the antibody responses to HIV-1 envelope B-cell epitopes in a synthetic T-B peptide construct.
Copyright © 1991 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.