A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

被引：698

作者：

Ekiert, Damian C. ^{[2
]}

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

Bhabha, Gira ^{[2
]}

Kwaks, Ted ^{[1
]}

Jongeneelen, Mandy ^{[1
]}

Yu, Wenli ^{[2
]}

Ophorst, Carla ^{[1
]}

Cox, Freek ^{[1
]}

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

Brandenburg, Boerries ^{[1
]}

Vogels, Ronald ^{[1
]}

Brakenhoff, Just P. J. ^{[1
]}

Kompier, Ronald ^{[1
]}

Koldijk, Martin H. ^{[1
]}

Cornelissen, Lisette A. H. M. ^{[3
]}

Poon, Leo L. M. ^{[4
,5
]}

Peiris, Malik ^{[4
,5
]}

Koudstaal, Wouter ^{[1
]}

Wilson, Ian A. ^{[2
,6
]}

Goudsmit, Jaap ^{[1
]}

机构：

[1] Crucell Holland BV, NL-2301 CA Leiden, Netherlands

[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[3] Wageningen Univ, Cent Vet Inst, NL-8221 RA Lelystad, Netherlands

[4] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China

[5] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China

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

来源：

SCIENCE | 2011年 / 333卷 / 6044期

关键词：

MONOCLONAL-ANTIBODIES; HEMAGGLUTININ; PH; RECOGNITION; PEPTIDE; H5N1; HA2;

D O I：

10.1126/science.1204839

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：

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.

引用

页码：843 / 850

页数：8

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