Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 Envelope glycoprotein trimers on neutralizing antibody induction

Virology. 2017 May:505:193-209. doi: 10.1016/j.virol.2017.02.024. Epub 2017 Mar 6.


Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits (PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to improve nAb responses by removing the N362 glycan that also lines the CD4bs. All 4 rabbits developed nAbs. One targeted the N197 glycan hole like our previous sera. Two sera depended on the N463 glycan, again suggesting CD4bs overlap. Heterologous boosts appeared to reduce nAb clashes with the N362 glycan. The fourth serum targeted a N362 glycan-sensitive epitope. VLP manufacture challenges prevented us from immunizing larger rabbit numbers to empower a robust statistical analysis. Nevertheless, trends suggest that targeted glycan removal may improve nAb induction by exposing new epitopes and that it may be possible to modify nAb specificity using rational heterologous boosts.

Keywords: Antibody; Env, trimer; Glycan; Gp120, neutralization; HIV-1; VLP; Vaccine.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / immunology*
  • Binding Sites / genetics
  • Binding Sites / immunology
  • CD4 Antigens / immunology*
  • Cell Line
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • HIV Antibodies / biosynthesis
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp160 / immunology*
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunization
  • Neutralization Tests
  • Rabbits


  • Antibodies, Neutralizing
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • HIV Envelope Protein gp41