title: Humanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1.
abstract: Hemagglutinin (HA), the major antigen on the surface of influenza viruses, is the primary target for neutralizing antibodies and vaccine design. However, frequent mutations in this gene allow the virus to evade host immune responses and conventional prophylaxis and treatment. In this report, we humanized 4D1 and 10F7 mouse monoclonal antibodies (mAbs) that, we had previously shown to display broad-spectrum neutralization to avian H5N1 virus. The genes of variable (V) regions of 4D1 and 10F7 mAbs were combined with constant region of human antibody to construct the chimeric antibodies (cAbs). The results of hemagglutinin inhibition (HI) and neutralization assays showed that 4D1 and 10F7 cAbs were functional and retained broad-spectrum reactivity. Antibody competitive ELISA and affinity tests indicated that the cAbs recognized the same epitope as the parent mAbs with similar affinity. In animal experiments, the 10F7 cAb showed full protection against lethal challenge of highly virulent avian H5N1 virus, A/BH Goose/QH/15C/2005, in all infected mice. These humanized broad-spectrum antibodies may be potentially important for the control of both current and future antigenic variants of H5N1 virus.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenxin
authors.initials: W
authors.lastname: Luo
authors.forename: Wai Lan
authors.initials: WL
authors.lastname: Wu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Fang
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.forename: Xun
authors.initials: X
authors.lastname: Gui
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.forename: J Wai-Kuo
authors.initials: JW
authors.lastname: Shih
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000276:immunology* / Q000627:therapeutic use; D001835:Body Weight; D018604:Epitope Mapping; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human; D051379:Mice; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region