Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies

被引：190

作者：

McCoy, Laura E. ^{[1
,2
,3
]}

van Gils, Marit J. ^{[4
]}

Ozorowski, Gabriel ^{[2
,5
]}

Messmer, Terrence ^{[1
,2
]}

Briney, Bryan ^{[1
,2
]}

Voss, James E. ^{[1
,2
]}

Kulp, Daniel W. ^{[1
,2
]}

Macauley, Matthew S. ^{[6
]}

Sok, Devin ^{[1
,2
]}

Pauthner, Matthias ^{[1
,2
]}

Menis, Sergey ^{[1
,2
]}

Cottrell, Christopher A. ^{[2
,5
]}

Torres, Jonathan L. ^{[2
,5
]}

Hsueh, Jessica ^{[1
,2
]}

Schief, William R. ^{[1
,2
]}

Wilson, Ian A. ^{[2
,5
]}

Ward, Andrew B. ^{[2
,5
]}

Sanders, Rogier W. ^{[4
,7
]}

Burton, Dennis R. ^{[1
,2
,8
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[3] UCL, Div Infect & Immun, London WC1E 6BT, England

[4] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[5] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[7] Cornell Univ, Weill Med Coll, New York, NY 10065 USA

[8] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2016年 / 16卷 / 09期

基金：

欧洲研究理事会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; DEPENDENT EPITOPE; HUMORAL IMMUNITY; RESPONSES; VACCINE; ESCAPE; POTENT; GP120; CELL; GLYCOPROTEINS;

D O I：

10.1016/j.celrep.2016.07.074

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP. 664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP. 664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.

引用

页码：2327 / 2338

页数：12

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