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HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen. [ABSTRACT FROM AUTHOR]

Keywords: human immunodeficiency virus; antibody; evolution; crystal structure; somatic hypermutation; framework EN human immunodeficiency virus antibody evolution crystal structure somatic hypermutation framework N.PAG N.PAG 1 11/20/20 20201118 NES 201118 In the original article, we neglected to include the funder NIGMS from the NIH, P30 GM124165 to NE-CAT beamlines; the funder NIH-ORIP HEI, S10OD021527 to the Eiger 16M detector on the 24-ID-E beam line; and the funder US DOE, DE-AC02-06CH11357 to APS. Human immunodeficiency virus, antibody, evolution, crystal structure, somatic hypermutation, framework. [Extracted from the article]