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: 7924019
• 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/7924019
• 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

这项修订后的两年资助计划已删除了包括动物工作在内的所有国外部分，成为一个完全国内的项目，重点是单独的马尔堡病毒GP蛋白工程和结晶以及与现有抗体的复合物。这笔赠款将导致通过GP针对马尔堡病毒的疫苗和药物设计的必要模板。可验证的将包括晶体和原子坐标，以及高产量的表达构建的马尔堡病毒GP和抗体抗原决定簇的初步映射上it. We最近确定了扎伊尔和苏丹埃博拉病毒GP，确定脆弱的，以前非靶向的丝状病毒表面抗原决定簇的晶体结构。对成功的乐观态度源于已有的许多针对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（Rev.11/07） 页面 1 续页格式