INDUCTION OF NEUTRALIZING ANTIBODIES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 USING SYNTHETIC PEPTIDE CONSTRUCTS CONTAINING AN IMMUNODOMINANT T-HELPER CELL DETERMINANT FROM VPR

Identification of immunodominant T-helper-cell determinants after natu ral infection is an important step in the design of immunogens for pot ential use in vaccination. Using cells from human immunodeficiency vir us type 1 (HIV-1)-infected individuals and a panel of peptides encompa ssing the sequence of the regulatory protein vpr from HIV-1, we identi fied the T-helper determinant QLLFIHFRIGCRHSR, which is active in 37.5 % of these individuals. To gain insight on the efficacy of this peptid e in helping induce neutralizing antibodies against a B-cell determina nt (BD), we synthesized constructs containing B- and T-cell determinan ts and tested them in BALB/c mice, the highest responders to the T-cel l determinant moiety among several strains tested. These immunogens in duced antibodies against two chosen B-cell determinants from HIV-1(III B) gp160 (amino acids 310-322 from the V3 loop of gp120 and 736-751 fr om gp41) that were able to neutralize HIV-1 infection in vitro. The hi ghest neutralization titer against HIV-1(IIIB) was obtained by immuniz ation with the homopolymer of the construct containing the T-cell epit ope from vpr and the B-cell epitope from the V3 loop. We believe that the immunodominant T-cell determinant from vpr is a promising epitope to consider in the design of future peptide vaccines.