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

Wan, Hongquan; Yang, Hua; Shore, David A.; Garten, Rebecca J.; Couzens, Laura; Gao, Jin; Jiang, Lianlian; Carney, Paul J.; Villanueva, Julie; Stevens, James; Eichelberger, Maryna C.

doi:10.1038/ncomms7114

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

Journal Article · Tue Feb 10 00:00:00 EST 2015 · Nature Communications

DOI:https://doi.org/10.1038/ncomms7114· OSTI ID:1245874

Wan, Hongquan ^[1]; Yang, Hua ^[2]; Shore, David A. ^[2]; Garten, Rebecca J. ^[2]; Couzens, Laura ^[1]; Gao, Jin ^[1]; Jiang, Lianlian ^[1]; Carney, Paul J. ^[2]; Villanueva, Julie ^[2]; Stevens, James ^[2]; Eichelberger, Maryna C. ^[1]

Food and Drug Administration, Silver Springs, MD (United States)
Centers for Disease Control and Prevention, Atlanta, GA (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); Food and Drug Administration and the Centers for Disease Control and Prevention

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1245874

Journal Information:: Nature Communications, Vol. 6, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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