Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / isolation & purification
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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 / chemistry
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Antigens, Viral / genetics
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Antigens, Viral / immunology*
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Binding Sites, Antibody
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Conserved Sequence
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Crystallography, X-Ray
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Epitopes / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / chemistry
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Humans
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Influenza A Virus, H3N2 Subtype / immunology
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Influenza A Virus, H7N7 Subtype / genetics
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Influenza A Virus, H7N7 Subtype / immunology
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Influenza A virus / immunology*
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Influenza Vaccines / immunology
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Influenza, Human / immunology
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Influenza, Human / prevention & control
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Influenza, Human / therapy
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Mice
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Neutralization Tests
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Protein Conformation
Substances
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Antibodies, Monoclonal
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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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Influenza Vaccines
Associated data
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GENBANK/JN093122
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GENBANK/JN093123
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PDB/3SDY