title: Human 4F5 single-chain Fv antibody recognizing a conserved HA1 epitope has broad neutralizing potency against H5N1 influenza A viruses of different clades.
abstract: Influenza A viruses present a significant threat to public health worldwide. High-affinity human scFv antibodies against a conserved epitope can potentially provide immunity to diverse viruses and protect against future pandemic viruses. A library of phage-displayed human scFv containing 6.0×10(8) members was generated from lymphocytes of H5N1 virus vaccinated individuals. Using the recombinant H5N1 virus hemagglutinin ectodomain (HA1), 4F5 scFv was identified with neutralizing activity against both clade 2 and 9 H5N1 viruses. In embryonated chicken eggs, the antiviral activity of 4F5 scFv conferred a 100% survival rate and at least a 62.5% survival rate against different clades of H5N1 viruses by pre-treatment and post-treatment, respectively. 4F5 scFv belongs to the VH-3-43 family according to the IMGT database, and a peptide (76)WLLGNP(81) containing half of an α-helix in HA1 was identified as the binding pocket. The conserved binding epitope of this novel broadly neutralizing scFv may become key in the design and implementation of vaccines or RNA interference against H5N1 viruses.
authors.affiliation: Key Laboratory of Antibody Technique, Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zeng
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Shi
authors.forename: Qiu
authors.initials: Q
authors.lastname: Jin
authors.forename: Feng
authors.initials: F
authors.lastname: Zhan
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiao
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002642:Chick Embryo / Q000821:virology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D019151:Peptide Library; D017433:Protein Structure, Secondary; D057127:Single-Chain Antibodies / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019151:Peptide Library; D057127:Single-Chain Antibodies
keywords: Antiviral effect; Broad neutralization; Conserved epitope; H5N1 influenza A viruses; α-Helix