Antibody Prophylaxis and Therapy of Flavivirus Infection

描述(由申请人提供)：该项目的总体目标是开发抗体疗法和预防措施，以治疗和预防危及生命的黄病毒感染。西尼罗河病毒是第一阶段研究的重点。我们的工作假设是，高滴度的抗膜蛋白抗体可以保护人类免受黄病毒的侵袭。被动免疫是一种公认的医学实践，可以预防感染。用专有的重组西尼罗河病毒包膜蛋白抗原免疫动物可诱导高滴度抗体。这些抗体可以保护小鼠免受致命剂量的西尼罗河病毒的感染。生出或感染老鼠。使用标准的马免疫和抗体纯化方案将产生保护性的抗包膜蛋白抗体。Ig G抗体、F(ab‘)2和Fab静脉注射。或者I.C.V将在嗜神经性WN病毒感染的小鼠模型中进行评估。第一阶段实验还将开始开发针对相关黄病毒包膜蛋白的中和抗体。在第二阶段，我们希望获得一种马抗体制剂的临床前数据，以保护人类和动物免受西尼罗河病毒的感染；生产针对相关黄病毒的保护性抗体；并开发人源化的抗膜蛋白单抗。该项目将为临床医生、公共卫生官员和兽医提供管理黄病毒暴发的新手段。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop antibody therapy and prophylaxis to treat and prevent life-threatening flavivirus infections. West Nile virus is the focus of Phase I studies. Our working hypothesis is that high titer anti-envelope protein antibodies can protect humans against flaviviruses. Passive immunization is an accepted medical practice that can protect against infection. Immunizing animals with a proprietary recombinant West Nile virus envelope protein antigen induces high titer antibodies. These antibodies protect mice from a lethal dose of West Nile virus when administered i.p. to natve or infected mice. Protective anti-envelope protein antibodies will be produced using standard equine immunization and antibody purification protocols. IgG antibody, F(ab')2 and Fab administered i.v. or i.c.v will be evaluated in a mouse model of neurotropic WN virus infection. Phase I experiments will also begin developing neutralizing antibodies to related flavivirus envelope proteins. In Phase II, we expect to obtain preclinical data on an equine antibody preparation to protect humans and animals from West Nile virus infection; produce protective antibodies for related flaviviruses; and develop humanized anti-envelope protein monoclonal antibodies. This project will provide clinicians, public health officials, and veterinarians with new means to manage flavivirus virus outbreaks.