title: Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.
abstract: 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.
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Wei
authors.forename: Weixu
authors.initials: W
authors.lastname: Meng
authors.forename: Haijiang
authors.initials: H
authors.lastname: Guo
authors.forename: Weiqi
authors.initials: W
authors.lastname: Pan
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D000918:Antibody Specificity; D002162:Camelus; D002460:Cell Line; D002845:Chromatography / Q000379:methods; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007473:Ion Channels / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D014763:Viral Matrix Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D000906:Antibodies; D007473:Ion Channels; D009841:Oligonucleotides; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins