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

Crooks, Ema T and Osawa , Keiko and Tong, Tommy Yuh Koon * and Grimley, Samantha L and Dai, Yang D and Whalen, Robert G and Kulp, Daniel W and Menis, Sergey and Schief, William R and Binley, James M (2017) Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction. Virology, 505. pp. 193-209. ISSN 0042 6822 (In Press)

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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 speciUcity using rational heterologous boosts.

Item Type: Article
Uncontrolled Keywords: HIV-1 Env; Trimer Gp120; Neutralization vaccine; VLP; Antibody; Glycan
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR355 Virology
Divisions: Sunway University > School of Science and Technology > Dept. Biological Sciences
Depositing User: Dr Janaki Sinnasamy
Date Deposited: 10 Mar 2017 01:22
Last Modified: 10 Mar 2017 01:22
URI: http://eprints.sunway.edu.my/id/eprint/479

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