Structures of Respiratory Syncytial Virus G Antigen Bound to Broadly-Neutralizing Antibodies
| Autor: | Lawrence M. Kauvar, Rebecca M. DuBois, Natasha L. George, Stanislav O. Fedechkin, Jacob T. Wolff |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.drug_class Protein Conformation 030106 microbiology Immunology CX3C Chemokine Receptor 1 Monoclonal antibody Virus Epitope Article 03 medical and health sciences Chemokine receptor Antigen Viral envelope Cell Line Tumor medicine Humans Antigens Viral chemistry.chemical_classification biology Chemokine CX3CL1 Antibodies Monoclonal General Medicine Virology Antibodies Neutralizing 030104 developmental biology chemistry Respiratory Syncytial Virus Human biology.protein Antibody Glycoprotein Viral Fusion Proteins |
| Popis: | Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective, RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD). Here we describe the co-crystal structures of two high-affinity, broadly-neutralizing human monoclonal antibodies bound to the RSV G CCD. The antibodies bind to neighboring conformational epitopes, which we named antigenic sites γ1 and γ2, that span a highly-conserved surface, illuminating an important region of vulnerability. We further show that isolated RSV G CCD activates the chemokine receptor CX3CR1 and that antibodies block this activity. These studies provide a template for rational vaccine design targeting this key contributor to RSV disease. |
| Databáze: | OpenAIRE |
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