Epitope-vaccines: A new strategy to induce high levels of neutralizing antibodies against HIV-1

Based on the experimental evidence that gp120 subunit vaccine did not prote ct individuals from HIV-1 infection, we suggested that epitope-vaccines of HIV-1 gp41 may be a new strategy to induce high levels of neutralizing anti bodies against HIV-1, and characterised immunogenicity of epitope-vaccines. Two epitopes, RILAVERYLKD-epitope (aa586-596) on the N-domain and ELDKWA-e pitope (aa669-674) on the C-domain of gp41, were demonstrated by us and oth ers to induce protective activity. After vaccination course, the RILAVERYLK D-dimer epitope-vaccine [C(RILAVERYLKDG)(2)-BSA] induced strong epitope-spe cific antibody response by about 1:25,600 dilution, and the ELDKWA-tetramer epitope-vaccine [C-(ELDKWAG)(4)-BSA] could yet induce strong antibody resp onse to ELDKWA-epitope by 1:12,800-25,600 dilution of antisera in mice, whi le rgp41 subunit vaccine induced very weak antibody response to both epitop es (1:400). In rabbit experiments, the titres of ELDKWA-epitope-specific an tibody induced by ELDKWA-epitope-vaccine [C-(ELDKWAG)(4)-BSA] reached to 1: 6,400, while rgp41 subunit vaccine induced very weak antibody response to t his epitope and to P1 and P2 peptides (1:400). Moreover, the ELDKWA-epitope -specific antibodies in mice and rabbit antisera induced by epitope-vaccine could very strongly interact with P2 peptide sequence-corresponding to the C-domain of gp41 (dilution by 1:25,600), and the RILAVERYLKD-epitope-speci fic antibodies in mice antisera induced by epitope-vaccine could also very strongly interact with P1 peptide sequence-corresponding to the N-domain of gp41 (dilution by 1:102,400). All these results provided experimental evid ence that epitope-vaccine may be a new general strategy to induce high leve ls of neutralizing antibodies against HIV-1 or other viruses.