HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope

Nat Commun. 2018 Mar 16;9(1):1111. doi: 10.1038/s41467-018-03565-6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Antibodies, Neutralizing / immunology*
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Gene Products, env / chemistry*
  • Gene Products, env / genetics
  • Gene Products, env / immunology*
  • HIV Antibodies / immunology*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Models, Molecular
  • Mutation

Substances

  • Antibodies, Neutralizing
  • Epitopes
  • Gene Products, env
  • HIV Antibodies