4O5L

Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus.

(2014) Nat Commun 5: 3614-3614

• PubMed: 24717798 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/ncomms4614
• Primary Citation of Related Structures:  
  4O5L


• PubMed Abstract: 
  

  Influenza viruses present a significant health challenge each year, as in the H3N2 epidemic of 2012-2013. Here we describe an antibody, F045-092, that possesses broadly neutralizing activity against the entire H3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. Crystal structures of F045-092 in complex with HAs from 1975 and 2011 H3N2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23-residue HCDR3 into the receptor-binding site that involves striking receptor mimicry. F045-092 extends its recognition to divergent subtypes, including H1, H2 and H13, using the enhanced avidity of its IgG to overcome lower-affinity Fab binding, as observed with other antibodies that target the receptor-binding site. This unprecedented level of antibody cross-reactivity against the H3 subtype can potentially inform on development of a pan-H3 vaccine or small-molecule therapeutics.

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Organizational Affiliation: 

1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.