Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein

PLoS One. 2011;6(12):e28309. doi: 10.1371/journal.pone.0028309. Epub 2011 Dec 2.


Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / chemistry*
  • Antibody Specificity
  • Camelus
  • Cell Line
  • Chromatography / methods
  • Dogs
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Gene Library
  • HEK293 Cells
  • Humans
  • Influenza A virus / immunology*
  • Ion Channels / chemistry
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Oligonucleotides / chemistry
  • Polymerase Chain Reaction / methods
  • Protein Binding
  • Protein Structure, Tertiary
  • Surface Plasmon Resonance
  • Viral Matrix Proteins / chemistry*


  • Antibodies
  • Ion Channels
  • M2 protein, Influenza A virus
  • Oligonucleotides
  • Viral Matrix Proteins