Immunotherapeutics against Marburg: Development, structural & functional anaylsis

这项修订后的两年资助取消了包括动物实验在内的所有外国成分，成为一个完全国内的项目，重点是马尔堡病毒GP蛋白工程和结晶，以及与已有抗体的结合。这笔赠款将通过GP产生针对马尔堡病毒的疫苗和药物设计的必要模板。交付成果将包括晶体和原子坐标，以及马尔堡病毒GP的高产表达构建物和抗体表位的初始定位。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上脆弱的、以前未靶向的表位。对成功的乐观态度源于已有的许多针对MARV的单克隆抗体，以及我们成功构建的另外两种三聚体丝状病毒GPs的晶体结构，每一种都与不同的单抗复合物。

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