ELNKWA-epitope specific antibodies induced by epitope-vaccine recognize ELDKWA- and other two neutralizing-resistant mutated epitopes on HIV-1 gp41

Based on the fact that monoclonal antibody (mAb) 2F5 recognizing ELDKWA-epi tope on HIV-1 gp41 separately or in combination with other mAbs showed pote nt neutralizing activity to a wide range of primary HIV-1 isolates in vivo and in vitro, but this epitope undergoes restricted mutation. ELNKWA is a n eutralizing-resistant mutated epitope. We induced ELNKWA-epitope-specific p olyclonal and monoclonal antibodies and studied the interaction of the anti bodies with ELDKWA-epitope and other two neutralizing-resistant mutated epi topes. The candidate ELNKWA-epitope-vaccine induced a high level of antibod ies to the ELNKWA-epitope-peptide. The ELNKWA-epitope-specific polyclonal a ntibodies bound not only the ELNKWA-, but also ELDKWA-, ELEKWA- and ELDEWA- epitope-peptides in ELISA-assay. Moreover, the antibodies also recognized f our C-domain-peptides (P5, P6, P7, P8) which contain these four epitopes, r espectively. Interestingly. an ELNKWA-epitope-specific monoclonal antibody (TH-Ab1) induced by the candidate ELNKWA-epitope-vaccine could also recogni ze the four C-domain-peptides containing ELNKWA-, ELDKWA-, ELEKWA- and ELDE WK-epitopes. These results indicate that the candidate ELNKWA-epitope-vacci ne could induce high levels of antibodies, which recognize the neutralizing epitope ELDKWA and three neutralizing-resistant mutated epitopes, suggesti ng that the candidate ELNKWA-epitope-vaccine may help to overcome the probl em of viral escape from neutralization through mutation at D or K position, and may be developed as an effective vaccine with a broad neutralizing act ivity against HIV-1. (C) 2001 Elsevier Science B.V. All rights reserved.