Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

Structure. 2020 Aug 4;28(8):897-909.e6. doi: 10.1016/j.str.2020.04.022. Epub 2020 May 19.


Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.

Keywords: broadly neutralizing antibodies; cryo-electron microscopy; glycans; glycosylation; human immunodeficiency virus; mass spectrometry; structure; vaccines.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antigen-Antibody Complex / chemistry
  • Broadly Neutralizing Antibodies / chemistry
  • Broadly Neutralizing Antibodies / immunology
  • Epitopes / chemistry*
  • Epitopes / genetics
  • Epitopes / immunology
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology
  • HIV-1 / immunology*
  • Humans
  • Molecular Docking Simulation
  • Mutation
  • Polysaccharides / chemistry*
  • Polysaccharides / immunology
  • env Gene Products, Human Immunodeficiency Virus / chemistry*
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • 2G12 monoclonal antibody
  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Broadly Neutralizing Antibodies
  • Epitopes
  • HIV Antibodies
  • Polysaccharides
  • env Gene Products, Human Immunodeficiency Virus