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Published Online 28 July 2011
< Science Express Index
Science DOI: 10.1126/science.1205669
Research Article
A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins
Davide Corti1,2,*,
Jarrod Voss3,*,
Steven J. Gamblin3,*,
Giosiana Codoni1,*,
Annalisa Macagno1,
David Jarrossay1,
Sebastien G. Vachieri3,
Debora Pinna1,
Andrea Minola1,
Fabrizia Vanzetta2,
Chiara Silacci1,
Blanca M. Fernandez-Rodriguez1,
Gloria Agatic2,
Siro Bianchi2,
Isabella Giacchetto-Sasselli1,
Lesley Calder3,
Federica Sallusto1,
Patrick Collins3,
Lesley F. Haire3,
Nigel Temperton4,
Johannes P. M. Langedijk5,?,
John J. Skehel3,?,
Antonio Lanzavecchia1,6,?
+ Author Affiliations
1Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
2Humabs BioMed SA, 6500 Bellinzona, Switzerland.
3Medical Research Council (MRC) National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
4Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent ME4 4TB, UK.
5Pepscan Therapeutics BV, Lelystad, 8243 RC, Netherlands.
6Institute of Microbiology, Eidgen?ssische Technische Hochschule (ETH) Z?rich, 8032 Z?rich, Switzerland.
+ Author Notes
↵? Present address: Crucell Holland BV, 2333 CN Leiden, Netherlands.
?To whom correspondence should be addressed. E-mail: lanzavecchia@irb.unisi.ch (A.L.); skeheljj@nimr.mrc.ac.uk (J.J.S.)
↵* These authors contributed equally to this work.
Abstract
The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
< Science Express Index
Science DOI: 10.1126/science.1205669
Research Article
A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins
Davide Corti1,2,*,
Jarrod Voss3,*,
Steven J. Gamblin3,*,
Giosiana Codoni1,*,
Annalisa Macagno1,
David Jarrossay1,
Sebastien G. Vachieri3,
Debora Pinna1,
Andrea Minola1,
Fabrizia Vanzetta2,
Chiara Silacci1,
Blanca M. Fernandez-Rodriguez1,
Gloria Agatic2,
Siro Bianchi2,
Isabella Giacchetto-Sasselli1,
Lesley Calder3,
Federica Sallusto1,
Patrick Collins3,
Lesley F. Haire3,
Nigel Temperton4,
Johannes P. M. Langedijk5,?,
John J. Skehel3,?,
Antonio Lanzavecchia1,6,?
+ Author Affiliations
1Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
2Humabs BioMed SA, 6500 Bellinzona, Switzerland.
3Medical Research Council (MRC) National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
4Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent ME4 4TB, UK.
5Pepscan Therapeutics BV, Lelystad, 8243 RC, Netherlands.
6Institute of Microbiology, Eidgen?ssische Technische Hochschule (ETH) Z?rich, 8032 Z?rich, Switzerland.
+ Author Notes
↵? Present address: Crucell Holland BV, 2333 CN Leiden, Netherlands.
?To whom correspondence should be addressed. E-mail: lanzavecchia@irb.unisi.ch (A.L.); skeheljj@nimr.mrc.ac.uk (J.J.S.)
↵* These authors contributed equally to this work.
Abstract
The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
