Immunogenicity of neutralizing epitopes on multiple-epitope vaccines against HIV-1

Based on our hypothesis that epitope vaccine may be a new strategy to induc e high levels of neutralization antibodies against HIV-l,we prepared multip le-epitope vaccines using three neutralizing epitopes (GPGRAFY, RILAVERYLKD and ELDKWA) of HIV-1 gp160, and characterized their immunogenicity. Peptid e 1 [C-G-(ELDKWA-GPGRAFY)(2)-K] and peptide 2 (CG-GPGRAFY-ELDKWA-G-RILAVERY LKD) were synthesized and conjugated with carrier protein bovine serum albu min (BSA). After vaccination antibody responses to these immunogens were in duced and evaluated by ELISA. The C-G-(ELDKWA-GPGRAFY)(2)-K-BSA (BSA: carri er protein) multiple-epitope vaccine induced a strong antibody response to the C-G-(ELDKWA-GPGRAFY)(2)-K peptide (antibody titer: 1:25,600) and C-(ELD KWAG)(4) peptide (antibody titer: 1:12,800), but a weak antibody response t o the C-(GPCGRAFY)(4) peptide. The CG-GP-GRAFY-ELDKWA-G-RILAVERYLKD-K-BSA ( BSA: carrier protein) multiple-epitope vaccine also induced strong antibody response to the CG-GPGRAFY-ELDKWA-G-RILAVERYLKD-K peptide (antibody titer: 1:25,600) and C-(ELLDKWAG)(4) peptide (antibody titer: 1:6,400), a very st rong response to C-(RIVALVERYLKD-G)2-K peptide (dilution: 1:102,400), and a very weak response to the C-(GPGRAFY)(4) peptide (dilution: 1:400) in mice . Both anti sera induced by both multiple-epitope vaccines interacted with the recombinant soluble gp41 (rgp41), but did not bind two control peptides . In comparison with both epitope vaccines, the rgp160 subunit vaccine coul d induce weak epitope-specific antibody response to these three epitopes on the three epitope peptides and V3, N-domain and C-domain peptides (dilutio n: 1:400-1:1,600). These results indicate that both multiple-epitope vaccin es could induce high levels of antibodies to both neutralizing epitopes RIL AVERYLKD and ELDKWA, while the GPGRAFY epitope on both vaccines appeared to have weak immunogenicity. Both multiple-epitope vaccines showed significan t potency on inducing high levels of epitope-specific neutralization antibo dies in comparison with rgp160 subunit vaccine. Copyright (C) 2000 S. Karge r AG, Basel.