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PMID: 21798894 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins.

Science (New York, N.Y.) ·Vol. 333 ·No. 6044 ·2011-08-12 ·Pages 850-6

Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, Vachieri SG, Pinna D, Minola A, Vanzetta F, Silacci C, Fernandez-Rodriguez BM, Agatic G, Bianchi S, Giacchetto-Sasselli I, Calder L, Sallusto F, Collins P, Haire LF, Temperton N, Langedijk JP, Skehel JJ, Lanzavecchia A

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.

MeSH Terms

Animals Antibodies, Neutralizing/immunology,isolation & purification Antibodies, Viral/immunology,isolation & purification Antibody Specificity Antigens, Viral/immunology Cells, Cultured Cross Reactions Crystallography, X-Ray Epitopes/immunology Ferrets Glycosylation Hemagglutinin Glycoproteins, Influenza Virus/immunology Humans Hydrophobic and Hydrophilic Interactions Immunization, Passive Immunoglobulin Variable Region/immunology Influenza A Virus, H1N1 Subtype/immunology Influenza A virus/immunology Influenza B virus/immunology Influenza, Human/immunology Mice Models, Molecular Molecular Sequence Data Orthomyxoviridae Infections/immunology,prevention & control,therapy Plasma Cells/immunology Protein Multimerization Protein Structure, Secondary

Chemicals

Antibodies, Neutralizing Antibodies, Viral Antigens, Viral Epitopes Hemagglutinin Glycoproteins, Influenza Virus Immunoglobulin Variable Region

Authors & Affiliations

23 authors, click to expand affiliations / ORCID

Corti Davide

Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.

Voss Jarrod

Gamblin Steven J

Codoni Giosiana

Macagno Annalisa

Jarrossay David

Vachieri Sebastien G

Pinna Debora

Minola Andrea

Vanzetta Fabrizia

Silacci Chiara

Fernandez-Rodriguez Blanca M

Agatic Gloria

Bianchi Siro

Giacchetto-Sasselli Isabella

Calder Lesley

Sallusto Federica

Collins Patrick

Haire Lesley F

Temperton Nigel

Langedijk Johannes P M

Skehel John J

Lanzavecchia Antonio

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1205669

Published

2011-08-12

Epub

2011-00-28

Pages

850-6

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

European Research Council · 250348 · International

Medical Research Council · G0600369 · United Kingdom

Medical Research Council · MC_U117584222 · United Kingdom

Wellcome Trust · United Kingdom

Databases

GENBANK

JN234430, JN234431, JN234432, JN234433, JN234434, JN234435, JN234436, JN234437, JN234438, JN234439, JN234440, JN234441, JN234442, JN234443, JN234444, JN234445, JN234446, JN234447, JN234448

Corrections

CommentIn

PMID: 21836007

CommentIn

PMID: 21959284

External Links

PubMed source DOI: 10.1126/science.1205669 View journal details

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A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins.

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