title: A fully human monoclonal antibody with novel binding epitope and excellent neutralizing activity to multiple human IFN-α subtypes: A candidate therapy for systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease short of effective therapeutic agents. A multitude of studies of SLE in the last decade have accentuated a central role of the interferon alpha (IFN-α) pathway in SLE pathogenesis. We report here a candidate therapeutic neutralizing antibody, AIA22, with a different binding epitope and discrepant neutralizing profile from the anti-multiple IFN-α subtype antibodies currently in clinical trials. AIA22 specifically interacts with multiple IFN-α subtypes, binds to the type I IFN receptor 2 (IFNAR2) recognition region of IFN-α (considered a novel antigen epitope), and effectively neutralizes the activity of almost all of the IFN-α subtypes (with the exception of IFN-α7) both in vitro and in vivo. Concurrently, structural modeling and computational design yielded a mutational antibody of AIA22, AIAmut, which exhibited substantially improved neutralizing activity to multiple IFN-α subtypes.
authors.affiliation: a Beijing Institute of Biotechnology ; Beijing , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Weiyi
authors.initials: W
authors.lastname: Qiu
authors.forename: Dadi
authors.initials: D
authors.lastname: Zeng
authors.forename: Junjie
authors.initials: J
authors.lastname: Yue
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Peitang
authors.initials: P
authors.lastname: Huang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000494:pharmacology; D000915:Antibody Affinity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D016898:Interferon-alpha
keywords: antigen epitope; computational design; interferon alpha; monoclonal antibody; neutralizing activity; systemic lupus erythematosus