Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor

被引：77

作者：

Kong, Leopold ^{[1
,4
,8
,9
]}

Ju, Bin ^{[2
,3
]}

Chen, Yajing ^{[5
]}

He, Linling ^{[5
]}

Ren, Li ^{[2
,3
]}

Liu, Jiandong ^{[2
,3
]}

Hong, Kunxue ^{[2
,3
]}

Su, Bin ^{[10
]}

Wang, Zheng ^{[2
,3
]}

Ozorowski, Gabriel ^{[1
,4
,8
,9
]}

Ji, Xiaolin ^{[2
,3
]}

Hua, Yuanzi ^{[1
,4
,8
,9
]}

Chen, Yanli ^{[2
,3
]}

Deller, Marc C. ^{[6
]}

Hao, Yanling ^{[2
,3
]}

Feng, Yi ^{[2
,3
]}

Garces, Fernando ^{[1
,4
,8
,9
]}

Wilson, Richard ^{[8
,9
]}

Dai, Kaifan ^{[5
]}

O'Dell, Sijy ^{[11
]}

McKee, Krisha ^{[11
]}

Mascola, John R. ^{[11
]}

Ward, Andrew B. ^{[1
,4
,8
,9
]}

Wyatt, Richard T. ^{[4
,5
,8
,9
]}

Li, Yuxing ^{[12
]}

Wilson, Ian A. ^{[1
,4
,7
,8
,9
]}

Zhu, Jiang ^{[4
,5
]}

Shao, Yiming ^{[2
,3
,13
,14
]}

机构：

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

[2] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Ctr AIDS STD Control & Prevent, Beijing 102206, Peoples R China

[3] Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 102206, Peoples R China

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

[5] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA

[7] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[8] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA

[10] Jiangsu Prov Ctr Dis Control & Prevent, Nanjing 210009, Jiangsu, Peoples R China

[11] NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA

[12] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA

[13] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China

[14] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

来源：

IMMUNITY | 2016年 / 44卷 / 04期

关键词：

BROADLY NEUTRALIZING ANTIBODIES; HIV-1; ENVELOPE; HIV-1-NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; SITE; GLYCOPROTEINS; VACCINE; IDENTIFICATION; VULNERABILITY;

D O I：

10.1016/j.immuni.2016.03.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.

引用

页码：939 / 950

页数：12

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