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
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
收藏
页码:843 / 850
页数:8
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