Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41.

摘要: The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few such Abs have been forthcoming. Only one anti-gp41 monoclonal Ab (MAb), 2F5, has described. Here we report on two MAbs that recognize a region immediately C-terminal the 2F5 epitope. Both were generated from HIV-1-seropositive donors, (Z13) an antibody phage display library, (4E10) as hybridoma. predominantly linear relatively conserved epitope, compete with each other binding to synthetic peptide derived gp41, bind HIV-1MN virions. By flow cytometry, these appear weakly infected cells this not perturbed by pretreatment soluble CD4. Despite apparent nature epitopes Z13 4E10, denaturation recombinant envelope protein reduces MAbs, suggesting some conformational requirements full expression. Most significantly, 4E10 are able neutralize selected primary isolates diverse subtypes HIV-1 (e.g., B, C, E). results suggest rather extensive gp41 close transmembrane domain accessible could form useful target design.