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Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

Author

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  • Hongquan Wan

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Hua Yang

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • David A. Shore

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • Rebecca J. Garten

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • Laura Couzens

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Jin Gao

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Lianlian Jiang

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Paul J. Carney

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • Julie Villanueva

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • James Stevens

    (National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention)

  • Maryna C. Eichelberger

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

Abstract

A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses.

Suggested Citation

  • Hongquan Wan & Hua Yang & David A. Shore & Rebecca J. Garten & Laura Couzens & Jin Gao & Lianlian Jiang & Paul J. Carney & Julie Villanueva & James Stevens & Maryna C. Eichelberger, 2015. "Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7114
    DOI: 10.1038/ncomms7114
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