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Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 Envelope glycoprotein trimers on neutralizing antibody induction.
- Source :
-
Virology [Virology] 2017 May; Vol. 505, pp. 193-209. Date of Electronic Publication: 2017 Mar 06. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Neutralizing biosynthesis
Binding Sites genetics
Binding Sites immunology
Cell Line
Epitopes genetics
Epitopes immunology
Female
HEK293 Cells
HIV Antibodies biosynthesis
Humans
Immunization
Neutralization Tests
Rabbits
Antibodies, Neutralizing immunology
CD4 Antigens immunology
HIV Antibodies immunology
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp160 immunology
HIV Envelope Protein gp41 immunology
HIV-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 505
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 28279830
- Full Text :
- https://doi.org/10.1016/j.virol.2017.02.024