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Published Online 7 July 2011
< Science Express Index
Science DOI: 10.1126/science.1204839
Research Article
A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses
Damian C. Ekiert1,*,
Robert H. E. Friesen2,*,
Gira Bhabha1,
Ted Kwaks2,
Mandy Jongeneelen2,
Wenli Yu1,
Carla Ophorst2,
Freek Cox2,
Hans J.W.M. Korse2,
Boerries Brandenburg2,
Ronald Vogels2,
Just P.J. Brakenhoff2,
Ronald Kompier2,?,
Martin H. Koldijk2,
Lisette A.H.M. Cornelissen3,
Leo L. M. Poon4,
Malik Peiris4,
Wouter Koudstaal2,?,
Ian A. Wilson1,5,?,
Jaap Goudsmit2
+ Author Affiliations
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2Crucell Holland BV, Archimedesweg 4-6, 2301 CA Leiden, The Netherlands.
3Central Veterinary Institute, Wageningen University, Lelystad, the Netherlands.
4Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
5The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
+ Author Notes
↵? Present address: FluConsult, Noordwijk, the Netherlands
?To whom correspondence should be addressed. E-mail: wilson@scripps.edu (I.A.W.); wouter.koudstaal@crucell.com (W.K.)
↵* These authors contributed equally to this work
Abstract
Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 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 VH1-69 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.
Received for publication 25 February 2011.
Accepted for publication 10 June 2011.
< Science Express Index
Science DOI: 10.1126/science.1204839
Research Article
A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses
Damian C. Ekiert1,*,
Robert H. E. Friesen2,*,
Gira Bhabha1,
Ted Kwaks2,
Mandy Jongeneelen2,
Wenli Yu1,
Carla Ophorst2,
Freek Cox2,
Hans J.W.M. Korse2,
Boerries Brandenburg2,
Ronald Vogels2,
Just P.J. Brakenhoff2,
Ronald Kompier2,?,
Martin H. Koldijk2,
Lisette A.H.M. Cornelissen3,
Leo L. M. Poon4,
Malik Peiris4,
Wouter Koudstaal2,?,
Ian A. Wilson1,5,?,
Jaap Goudsmit2
+ Author Affiliations
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2Crucell Holland BV, Archimedesweg 4-6, 2301 CA Leiden, The Netherlands.
3Central Veterinary Institute, Wageningen University, Lelystad, the Netherlands.
4Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
5The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
+ Author Notes
↵? Present address: FluConsult, Noordwijk, the Netherlands
?To whom correspondence should be addressed. E-mail: wilson@scripps.edu (I.A.W.); wouter.koudstaal@crucell.com (W.K.)
↵* These authors contributed equally to this work
Abstract
Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 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 VH1-69 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.
Received for publication 25 February 2011.
Accepted for publication 10 June 2011.
