title: A cross-protective mAb recognizes a novel epitope within the flavivirus NS1 protein.
abstract: Despite a resurgence of flavivirus infections worldwide, no approved therapeutic agent exists for any member of the genus. While cross-reactive antibodies with therapeutic potential against flaviviruses have been generated, the majority of them are anti-E antibodies with the potential to cause antibody-dependent enhancement of flavivirus infection and disease. We described previously mAbs against the non-structural NS1 protein of the West Nile virus (WNV) that were protective in mice when administered pre- or post-infection of WNV. Here, we demonstrate that one of these mAbs (16NS1) cross-reacted with Japanese encephalitis virus (JEV) and exhibited protective activity against a lethal JEV infection. Overlapping peptide mapping analysis combined with site-specific mutations identified a novel epitope ¹¹⁶KAWGKSILFA¹²⁵ and critical amino acid residues (¹¹⁸W and ¹²²I) for 16NS1 mAb binding. These results may facilitate the development of a broadly therapeutic mAb that lacks enhancing potential and/or subunit-based vaccine against flaviviruses that target the NS1 protein.
authors.affiliation: Institute for Medical Science, Chonbuk National University Medical School, Chonju, Chonbuk 561-180, Republic of Korea.|Department of Microbiology and Immunology, Chonbuk National University Medical School, Chonju, Chonbuk 561-180, Republic of Korea.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences and Utah Science Technology and Research (USTAR), College of Agriculture, Utah State University, Logan, UT 84322-4815, USA.|Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Song
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences and Utah Science Technology and Research (USTAR), College of Agriculture, Utah State University, Logan, UT 84322-4815, USA.|Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Yun
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Woo
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences and Utah Science Technology and Research (USTAR), College of Agriculture, Utah State University, Logan, UT 84322-4815, USA.|Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Institute for Medical Science, Chonbuk National University Medical School, Chonju, Chonbuk 561-180, Republic of Korea.|Department of Microbiology and Immunology, Chonbuk National University Medical School, Chonju, Chonbuk 561-180, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Chung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D056738:Cross Protection; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000821:virology; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins