title: Structural Basis of Zika Virus-Specific Antibody Protection.
abstract: Zika virus (ZIKV) infection during pregnancy has emerged as a global public health problem because of its ability to cause severe congenital disease. Here, we developed six mouse monoclonal antibodies (mAbs) against ZIKV including four (ZV-48, ZV-54, ZV-64, and ZV-67) that were ZIKV specific and neutralized infection of African, Asian, and American strains to varying degrees. X-ray crystallographic and competition binding analyses of Fab fragments and scFvs defined three spatially distinct epitopes in DIII of the envelope protein corresponding to the lateral ridge (ZV-54 and ZV-67), C-C' loop (ZV-48 and ZV-64), and ABDE sheet (ZV-2) regions. In vivo passive transfer studies revealed protective activity of DIII-lateral ridge specific neutralizing mAbs in a mouse model of ZIKV infection. Our results suggest that DIII is targeted by multiple type-specific antibodies with distinct neutralizing activity, which provides a path for developing prophylactic antibodies for use in pregnancy or designing epitope-specific vaccines against ZIKV.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Estefania
authors.initials: E
authors.lastname: Fernandez
authors.affiliation: Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Dowd
authors.affiliation: Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Speer
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Platt
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gorman
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Govero
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nelson
authors.affiliation: Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: fremont@wustl.edu.
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry*; D018604:Epitope Mapping; D000939:Epitopes; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D014759:Viral Envelope Proteins / Q000737:chemistry*; D000071244:Zika Virus / Q000737:chemistry* / Q000145:classification / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins