Antibody Prophylaxis and Therapy of Flavivirus Infection

黄病毒感染的抗体预防和治疗

• 批准号: 6890457
• 负责人: Raymond Allen Koski
• 金额: $ 46.96万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6890457
• 关键词: Flaviviridae; West Nile virus; antibody neutralization test; arthropod borne communicable disease; biotechnology; communicable disease control; dengue virus; dosage; emerging infectious disease; encephalitis virus; horses; immunofluorescence technique; immunoglobulin G; immunoglobulin structure; immunologic substance development /preparation; immunopharmacology; immunotherapy; laboratory mouse; laboratory rabbit; microorganism disease chemotherapy; neutralizing antibody; nonhuman therapy evaluation; passive immunization; recombinant proteins; virus antigen; virus diseases; virus envelope; virus protein; yellow fever virus

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.

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，以治疗和预防威胁生命的黄素感染。西尼罗河病毒是I期研究的重点。我们的工作假设是，高滴度抗固定蛋白抗体可以保护人类免受黄酮病毒​​的侵害。被动免疫是一种可以预防感染的公认的医学实践。用专有的重组西尼罗河膜蛋白抗原免疫动物可诱导高滴度抗体。当服用腹腔注射时，这些抗体可保护小鼠免受西尼罗河病毒的致命剂量。到NATVE或感染的小鼠。使用标准的马免疫和抗体纯化方案产生保护性抗Envelope蛋白抗体。 IgG抗体F（AB'）2和Fab施用了i.v.或I.C.V将在神经性WN病毒感染的小鼠模型中评估。第一阶段的实验还将开始开发与相关黄素包膜蛋白的中和抗体。在第二阶段，我们期望获得有关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感染的影响。产生针对相关黄病毒的保护性抗体；并开发人性化的抗Envelope蛋白单克隆抗体。该项目将为临床医生，公共卫生官员和兽医提供管理Flavivirus病毒爆发的新手段。