HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies

Some neutralizing epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro. But only very low levels of antibodies to these epitopes were determined in the HIV-1 infected individuals. In this study, the alumi num (alum) adjuvant to increase the immunogenicity of the neutralizing epit opes was used. Three epitope-peptides [C-(ELDKWAG)(4). C-(RILAVERYLKD-G)(2) and C-(GPGRAFY)(2)], which contain three epitopes (ELDKWA, RILAVERYLKD, GP GRAFY) from the HIV-I Env proteins, were synthesized and conjugated to carr ier protein keyhole limpet hemocyanin (KLH). The epitope-vaccines C-(ELDKWA G)(4)-KLH and C(RILAVERYLKD-G)(2)-KLH in alum induced high levels of epitop e-specific antibodies recognizing the epitopes from epitope-peptides C-(ELD KWAG)(4) and C-(RILAVERYLKD-G)(2). as well as the gp41 C-domain peptides P2 [C TSLIHSLIEESQNQQEKNEQELLELDKWA (aa 646-673)] and P1 [LQARILAVERYLKDQQL ( aa 583-599)] and the recombinant soluble gp41 (rsgp41) bearing both epitope s (antibody titer in rabbit sera was 1:12800-25,500 dilution). Immunoblotti ng analysis demonstrated that the antibodies in both antisera bound to rsgp 41, indicating that both antibodies recognized the natural epitopes on rsgp 41 protein. The epitope-vaccines C-(GPGRAFY)(2)-KLH induced moderate GPGRAF Y epitope-specific antibody response with a titer of 1:6400. In contrast, a s it was demonstrated in previous studies, the immunization with rgp160 ind uced weak antibody response to these three epitopes (titer of 1:400-1600). This suggests that epitope-peptides conjugated to KLH when infected with al um significantly increases immunogenicity of gp41 neutralizing epitopes pro viding a hope for the development of an HIV-1 vaccine. (C) 2001 Elsevier Sc ience B.V. All rights reserved.