Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth

Cell Rep. 2018 Oct 23;25(4):893-908.e7. doi: 10.1016/j.celrep.2018.09.087.


Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses. Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth. Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies. Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts. Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.

Keywords: HIV-1 envelope; glycan shield; neutralizing antibodies; transmitted founder; vaccine design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing / metabolism*
  • Computational Biology
  • Conserved Sequence
  • HEK293 Cells
  • HIV-1 / metabolism*
  • Humans
  • Kinetics
  • Models, Molecular
  • Neutralization Tests
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • Antibodies, Neutralizing
  • Polysaccharides
  • env Gene Products, Human Immunodeficiency Virus