title: Chimerization and characterization of a monoclonal antibody with potent neutralizing activity across multiple influenza A H5N1 clades.
abstract: The persistent evolution and circulation of highly pathogenic avian influenza H5N1 viruses pose a serious threat to global heath and hamper pandemic preparedness through conventional vaccine strategies. Combination passive immunotherapy using non-competing neutralizing antibodies has been proposed as a viable alternative to provide broad protection against drift variants. This necessitates the pre-pandemic production and characterization of potently neutralizing monoclonal antibodies (MAbs). One such antibody, MAb 9F4 was shown to provide heterologous protection against multiple H5N1 clade viruses, including one of the recently designated subclades, namely 2.3.4, through binding to a novel epitope, warranting its further development and characterization as a therapeutic candidate. In this study, the conversion of MAb 9F4 from mouse IgG2b to mouse-human chimeric (xi) IgG1 and IgA1 was achieved. These chimeric MAb versions were found to retain high degrees of binding and neutralizing activity against H5N1. The demonstration that xi-IgA1-9F4 retains a fairly high level of neutralizing activity, which is ∼10-fold lower than the corresponding xi-IgG1 isotype, suggests that this MAb could be further developed and engineered for intranasal administration.
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Tze-Minn
authors.initials: TM
authors.lastname: Mak
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.affiliation: Infrastructure, Technology and Translational Division, Institute of Molecular and Cell Biology, A∗STAR, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore. Electronic address: Yee_Joo_TAN@NUHS.edu.sg.
authors.forename: Yee-Joo
authors.initials: YJ
authors.lastname: Tan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins
keywords: Hemagglutinin; Influenza H5N1; Neutralizing monoclonal antibodies