Induction of high levels of antibodies recognizing the neutralizing epitope ELDKWA and the D- or K-position-mutated epitopes by candidate epitope vaccines against HIV-1

Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a significant neutralization potency against 90% of the investigated viruses of African, Asian, American, and European strains, but the antibody respons es to the epitope 2F5 in HIV-l-infected individuals were very low. We attem pted to induce high levels of epitope-specific antibodies to ELDKWA and its three mutated epitopes by candidate epitope vaccines. The four candidate e pitope vaccines all induced strong antibody responses at dilutions from abo ut 1:6,400 to 1:25,600. We tested the cross-reactions between these antiser a and four epitope peptides. The ELDKWA-specific antisera showed strong cro ss-reactivity with three neutralizing-resistant mutated epitopes which cont ain changes in the D or K positions of the epitope sequence. Virus variants containing these changes could escape neutralization by monoclonal antibod y 2F5. In immunoblotting analysis, the ELDKWA. ELDEWA, and ELEKWA epitope s pecific antibodies all recognized rsgp41 which confirms that the antibodies against both mutated epitopes, ELDEWA and ELEKWA, could cross-react with t he native epitope on rsgp41. Although it is not clear whether the polyclona l antibodies induced by the ELDKWA epitope vaccine could neutralize the mut ated viruses containing these mutated epitopes, it is conceivable that epit ope vaccines based on mutated epitopes could induce strong antibody respons es with predefined epitope specificity to neutralize mutated viruses contai ning the mutated epitope. An epitope vaccine, using different epitopes incl uding mutated epitopes, could provide a new concept for developing a new va ccine against HIV-1. Copyright (C) 2000 S. Karger AG. Basel.