Studies On Neutralizing Epitope ELDKWA Of HIV-1 Gp41 And The Monoclonal Antibodies Induced

The epitope ELDKWA, which is located on transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1), is an important neutralizing epitope, and its binding human monoclonal antibody (mAb) 2F5 has a broad neutralizing activity. However, several reports show that the epitope-specific mAbs induced by constructed immunogens don't exhibit the same neutralizing activities as human mAb 2F5. To give the explanation of the result, this thesis focuses on the ELDKWA epitope and its binding mAbs, investigates the properties of mAbs.In this study, we chose the important neutralizing epitope ELDKWA as target, designed epitope-specific peptide antigens and identified monoclonal antibodies. We found that, (1) the effect of antibody response was related to the design of immunogens, and there could be remarkable differences in binding affinities with recombinant soluble gp41 (rsgp41) even when the antibodies were induced by the same epitope-specific peptide antigen. (2) These mAbs showed different inhibition activities in HIV-1 Env mediated cell-cell fusion assay. (3) In the neutralization assay (previous work) and pseudovirus pneutralization assay, different mAbs showed remarkable difference in neutralizing activities, the mAbs neutralizing HIV-1 B-clade primary isolate 92US657 couldn't neutralize B-clade pseudovirus JRFL which is constructed by transfection, meanwhile, the mAbs neutralizing pserdivirus didn't have 92US657 neutralizing activity. These results suggested that the binding ability with antigens, inhibition activity to cell-cell fusion, neutralizing ability and activity of mAbs focused on the same epitope could be affected by sequences of different viruses or structures of antibodies.