A common solution to group 2 influenza virus neutralization

被引：150

作者：

Friesen, Robert H. E. ^{[1
]}

Lee, Peter S. ^{[2
,3
]}

Stoop, Esther J. M. ^{[1
]}

Hoffman, Ryan M. B. ^{[2
]}

Ekiert, Damian C. ^{[2
]}

Bhabha, Gira ^{[2
]}

Yu, Wenli ^{[2
]}

Juraszek, Jarek ^{[1
]}

Koudstaal, Wouter ^{[1
]}

Jongeneelen, Mandy ^{[1
]}

Korse, Hans J. W. M. ^{[1
]}

Ophorst, Carla ^{[1
]}

Brinkman-van der Linden, Els C. M. ^{[1
]}

Throsby, Mark ^{[1
]}

Kwakkenbos, Mark J. ^{[4
]}

Bakker, Arjen Q. ^{[4
]}

Beaumont, Tim ^{[4
]}

Spits, Hergen ^{[4
]}

Kwaks, Ted ^{[1
]}

Vogels, Ronald ^{[1
]}

Ward, Andrew B. ^{[2
]}

Goudsmit, Jaap ^{[1
]}

Wilson, Ian A. ^{[2
,3
]}

机构：

[1] Janssen Ctr Excellence Immunoprophylaxis, Crucell Vaccine Inst, NL-2333 CN Leiden, Netherlands

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

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

[4] AIMM Therapeut, NL-1105 BA Amsterdam, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 01期

基金：

美国国家卫生研究院;

关键词：

antibody recognition; X-ray crystallography; electron microscopy; RECEPTOR-BINDING SITE; MEMORY B-CELLS; ANTIBODY RECOGNITION; A VIRUSES; HEMAGGLUTININ; EPITOPE; MICE; VULNERABILITY; INFECTION; PROSPECTS;

D O I：

10.1073/pnas.1319058110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.

引用

页码：445 / 450

页数：6

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