Immunotherapeutics against Marburg: Development, structural & functional anaylsis

针对马尔堡病毒的免疫疗法：发展、结构

• 批准号: 7644642
• 负责人: Erica Ollmann Saphire
• 金额: $ 62.99万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7644642
• 关键词: Animals; Antibodies; Categories; Cell membrane; Color; Complex; Crystallization; Democratic Republic of the Congo; Development; Drug Design; Engineering; Epitopes; Filovirus; Frankfurt-Marburg Syndrome Virus; Future; Glycoproteins; Goals; Grant; Human; Immunization; Immunologic Surveillance; Immunotherapeutic agent; International Aspects; Laboratories; Maps; Marburg virus GP-protein; Membrane; Monoclonal Antibodies; Protein Engineering; Proteins; Shapes; Shock; Side; Site; Structure; Sudan; Surface; Techniques; Therapeutic antibodies; Time; Vaccines; Viral; Viral Hemorrhagic Fevers; Virion; Virus; Work; insight; neutralizing antibody; optimism; pathogen; protein complex; stem; success; therapeutic development

This revised two year grant has removed all foreign components including animal work to become a fully domestic project focusing on Marburg virus GP protein engineering and crystallization alone and in complex with antibodies already in existence. This grant will result in the necessary templates for vaccine and drug design against Marburg virus through GP. Deliverables will include crystals and atomic coordinates, as well as high yield expression constructs of Marburg virus GP and initial mapping of antibody epitopes on it. We have recently determined crystal structures of both Zaire and Sudan ebolavirus GP, which identify vulnerable, previously untargeted epitopes on the filoviral surface. Optimism for success stems form numerous monoclonal antibodies against MARV already available and our successful crystal structures of two other trimeric, filovirus GPs, each in complex with a different mAb. PHS 398/2590 (Rev. 11/07) Page 1 Continuation Format Page

这项修订后的两年期拨款删除了包括动物工作在内的所有外国成分，成为一个完全国内的项目，专注于马尔堡病毒 GP 蛋白质工程和结晶，以及与现有抗体的复合物。这笔赠款将产生通过全科医生针对马尔堡病毒进行疫苗和药物设计所需的模板。可交付成果将包括晶体和原子坐标，以及马尔堡病毒 GP 的高产表达构建体及其上抗体表位的初始图谱。我们最近确定了扎伊尔和苏丹埃博拉病毒 GP 的晶体结构，该结构识别了丝状病毒表面上脆弱的、以前未靶向的表位。对成功的乐观情绪源于已有的大量针对 MARV 的单克隆抗体，以及我们成功的另外两种三聚体丝状病毒 GP 的晶体结构，每种都与不同的 mAb 复合。 PHS 398/2590（修订版。11/07） 页 1 延续格式页