Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design

被引：150

作者：

Andrabi, Raiees ^{[1
,2
,3
]}

Voss, James E. ^{[1
,2
,3
]}

Liang, Chi-Hui ^{[1
,2
,3
]}

Briney, Bryan ^{[1
,2
,3
]}

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

Wu, Chung-Yi ^{[4
]}

Wong, Chi-Huey ^{[4
]}

Poignard, Pascal ^{[1
,2
]}

Burton, Dennis R. ^{[1
,2
,3
,5
,6
]}

机构：

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

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

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

[4] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

[5] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02114 USA

[6] Harvard Univ, Boston, MA 02114 USA

来源：

IMMUNITY | 2015年 / 43卷 / 05期

关键词：

STRUCTURAL BASIS; V1/V2; DOMAIN; RECOGNITION; EPITOPE; GP120; MATURATION; REVEAL; TRIMER; PG16; PG9;

D O I：

10.1016/j.immuni.2015.10.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Broadly neutralizing antibodies (bnAbs) directed to the V2 apex of the HIV envelope (Env) trimer isolated from individual HIV-infected donors potently neutralize diverse HIV strains, but strategies for designing immunogens to elicit bnAbs have not been identified. Here, we compared four prototypes (PG9, CH01, PGT145, and CAP256.VRC26.09) of V2 apex bnAbs and showed that all recognized a core epitope of basic V2 residues and the glycan-N160. Two prototype bnAbs were derived from VH-germlines that were 99% identical and used a common germline D-gene encoded YYD-motif to interact with the V2-epitope. We identified isolates that were neutralized by inferred germline (iGL) versions of three of the prototype bnAbs. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response. These studies illustrate a strategy to transition from panels of bnAbs to vaccine candidates.

引用

页码：959 / 973

页数：15

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