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

被引：27

作者：

Crooks, Ema T. ^{[1
]}

Osawa, Keiko ^{[1
]}

Tong, Tommy ^{[1
,7
]}

Grimley, Samantha L. ^{[1
]}

Dai, Yang D. ^{[2
]}

Whalen, Robert G. ^{[5
]}

Kulp, Daniel W. ^{[3
,4
]}

Menis, Sergey ^{[3
,4
]}

Schief, William R. ^{[3
,4
,6
]}

Binley, James M. ^{[1
]}

机构：

[1] San Diego Biomed Res Inst, 10865 Rd Cure, San Diego, CA 92121 USA

[2] Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[5] Altravax Inc, 725 San Aleso Ave,Suite 2, Sunnyvale, CA 94085 USA

[6] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

[7] Sunway Univ, Sch Sci & Technol, Dept Biol Sci, 5 Jalan Univ, Bandar Sunway 47500, Selangor Darul, Malaysia

来源：

VIROLOGY | 2017年 / 505卷

关键词：

HIV-1; Env; trimer; Gp120; neutralization; Vaccine; VLP; Antibody; Glycan; VIRUS-LIKE PARTICLES; PROXIMAL EXTERNAL REGION; B-CELL RECEPTORS; MONOCLONAL-ANTIBODIES; POTENT NEUTRALIZATION; BROAD NEUTRALIZATION; MATURATION PATHWAY; IMMUNOGEN DESIGN; GP120; GERMLINE;

D O I：

10.1016/j.virol.2017.02.024

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：193 / 209

页数：17

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