An Affinity-Enhanced Neutralizing Antibody against the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 Recognizes an Epitope between Those of 2F5 and 4E10

摘要: The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 bears the epitopes two broadly neutralizing antibodies (Abs), 2F5 and 4E10, making it a target for vaccine design. A third Ab, Fab Z13, had previously been mapped to an epitope that overlaps those 4E10 but only weakly neutralizes limited set primary isolates. Here, libraries Z13 variants displayed on phage were engineered affinity selected against MPER peptide recombinant gp41. high-affinity variant, designated Z13e1, was isolated found be approximately 100-fold improved over parental not in binding antigens also neutralization potency sensitive HIV-1. Alanine scanning residues 664 680 revealed N671 D674 are crucial recognition as well HIV-1 by Z13e1. Ab competition studies truncation peptides indicate Z13e1 binds with high between overlapping minimal WASLWNWFDITN. Still, remained about order magnitude less potent than several isolates pseudotyped sum our molecular analyses suggests segment is exposed functional envelope trimer access specific within this limited. Thus, ability MPER-bearing immunogens elicit HIV-1-neutralizing Abs may depend part recapitulating particular constraints imposes which binds.