Immunotherapeutics against Marburg: Development, structural & functional anaylsis

这一修订后的两年拨款去掉了所有外国成分，包括动物工作，成为一个完全国内的项目，专注于马尔堡病毒GP蛋白工程和结晶，以及与现有抗体的复合体。这笔赠款将通过GP为针对马尔堡病毒的疫苗和药物设计提供必要的模板。交付内容将包括晶体和原子坐标，以及马尔堡病毒GP的高产量表达构建体和其上抗体表位的初步映射。我们最近确定了扎伊尔和苏丹埃博拉病毒GP的晶体结构，确定了丝状病毒表面以前未靶向的脆弱表位。对成功的乐观源于许多已有的针对Marv的单抗，以及我们成功的另外两个三聚体丝状病毒GP的晶体结构，每个都与不同的mAb形成复合体。 PHS 398/2590(11/07版) 页面 1 续订格式页面

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