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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Neutralizing / immunology*
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Antibodies, Neutralizing / isolation & purification
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Antibodies, Viral / immunology*
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Antibodies, Viral / isolation & purification
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Antibody Specificity
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Antigens, Viral / immunology*
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Cells, Cultured
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Cross Reactions
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Crystallography, X-Ray
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Epitopes / immunology
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Ferrets
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Glycosylation
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Immunization, Passive
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Immunoglobulin Variable Region / immunology
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Influenza A Virus, H1N1 Subtype / immunology
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Influenza A virus / immunology*
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Influenza B virus / immunology
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Influenza, Human / immunology
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Mice
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Models, Molecular
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Molecular Sequence Data
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Orthomyxoviridae Infections / therapy
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Plasma Cells / immunology
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Protein Multimerization
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Protein Structure, Secondary
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Antigens, Viral
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Epitopes
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Hemagglutinin Glycoproteins, Influenza Virus
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Immunoglobulin Variable Region
Associated data
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GENBANK/JN234430
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GENBANK/JN234431
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GENBANK/JN234432
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GENBANK/JN234433
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GENBANK/JN234434
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GENBANK/JN234435
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GENBANK/JN234436
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GENBANK/JN234437
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GENBANK/JN234438
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GENBANK/JN234439
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GENBANK/JN234440
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GENBANK/JN234441
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GENBANK/JN234442
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GENBANK/JN234443
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GENBANK/JN234444
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GENBANK/JN234445
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GENBANK/JN234446
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GENBANK/JN234447
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GENBANK/JN234448