Immunological responses to emerging phlebo- and arenaviruses

新出现的新世界病毒和静脉病毒对人类健康构成威胁，目前尚无预防性疫苗或治疗方法。一旦感染以前未暴露的人类宿主，这些病原体通常会导致疾病迅速进展并导致高死亡率。这些病毒表面显示的病毒糖蛋白是宿主免疫反应的主要决定因素，因此是抗病毒和疫苗设计的主要靶点。这项工作的目的是在分子水平上研究针对这些病毒糖蛋白的抗体反应，目的是分离和表征可以靶向和阻止病毒感染周期的单克隆抗体。这项工作的一个特别重点是分离单克隆抗体，它可以结合和（交叉）中和来自同一家族的几种生物医学上重要的病毒。在分离单克隆抗体后，我们将应用x射线晶体学和其他生物物理工具来确定针对病毒表面的中和表位。与成功开发治疗埃博拉病毒感染的单克隆抗体鸡尾酒类似，这项工作中产生的数据和试剂将为治疗这些危险病原体群体提供一个平台。

Emerging New World arena- and phlebo-viruses are threats to human health for which there are no preventative vaccines or therapeutic treatments. Upon infection of a previously unexposed human host, such pathogens often cause rapid disease progression and result in high mortality rates. The viral glycoproteins displayed on the surface of these viruses are the primary determinants of the host immune response and thus lead targets in antiviral and vaccine design. The objective of this work is to study the antibody response against these viral glycoproteins, at a molecular level, with the aim of isolating and characterizing monoclonal antibodies that can target and prevent the virus infection cycle. A particular emphasis of this work is to isolate monoclonal antibodies, which can bind and (cross)-neutralise several biomedically important viruses from the same families. Following isolation of monoclonal antibodies, we will apply X-ray crystallography and other biophysical tools to define neutralising epitopes targeted on the virus surface. By analogy to the success in development of monoclonal antibody cocktails to treat Ebola virus infection, the data and reagents produced in this work will provide a platform by which to therapeutically target these dangerous groups of pathogens.