Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design

Cell Rep. 2018 Jun 12;23(11):3249-3261. doi: 10.1016/j.celrep.2018.05.046.


Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex.

Keywords: HIV; Protocol C; broadly neutralizing antibody; cryo-EM; evolution; structure.

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

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology
  • AIDS Vaccines / metabolism*
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / metabolism*
  • Binding Sites, Antibody
  • Cryoelectron Microscopy
  • Epitopes / chemistry
  • Epitopes / immunology
  • Evolution, Molecular*
  • Glycosylation
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology
  • HIV Antibodies / metabolism*
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / metabolism*
  • Humans
  • Molecular Docking Simulation
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus