NEUTRALIZING ANTIBODIES AGAINST ORTHOPOX VIRUSES

中和正痘病毒抗体

• 批准号: 6216810
• 负责人: PAUL W PARREN
• 金额: $ 33.74万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6216810
• 关键词: Macaca fascicularis; Poxviridae; Poxviridae disease; bioterrorism /chemical warfare; cooperative study; laboratory mouse; neutralizing antibody; nonhuman therapy evaluation; vaccine development; vaccinia virus

There is concern that variola virus, the causative agent of smallpox which was eradicated as a human pathogen more than two decades ago, forms a threat to humans once again, this time as an agent of bioterrorism. The use of variola virus in a bioterrorist attack would be met by the use of the licensed live vaccinia virus vaccine. This vaccine may cause serious side effects which can be successfully treated with vaccinia immune globulin (VIG) derived from hyperimmune individuals. VIG however is in short supply and future availability is uncertain, and in addition suffers from the general concerns of using human blood products for therapeutic applications. This proposal aims to prepare and characterize human monoclonal antibodies against vaccinia virus which, likely formulated as an antibody cocktail, will constitute a replacement for VIG. We will isolate neutralizing antibodies against both infectious forms of vaccinia virus, i.e. intracellular mature virus (IMV) and extracellular enveloped virus (EEV). We will place particular emphasis on isolating antibodies against EEV, as EEV mediates dissemination of infection and is the viral form against which protective immune responses are directed. Inactivation of vaccinia virus will be studied in vitro and in vivo, and will be aimed at designing an antibody cocktail that provides protection against vaccinia virus infection in pre-exposure and post- exposure immunopropylaxis. The antibody cocktail designed may provide a treatment for smallpox itself. To examine the impact of passive immunization in immunoprophylaxis and immunotherapy of a smallpox-like disease in a non-human primate model, we will use an experimental model of monkeypox virus infection

人们担心，二十多年前被根除为人类病原体的天花的病毒药物，这是对人类的威胁，这次是生物恐怖主义的代理。 通过使用许可的活乳清病毒疫苗，可以在生物恐怖攻击中使用Variola病毒。 该疫苗可能会引起严重的副作用，可以用源自超免疫个体的免疫球蛋白（VIG）成功治疗。 但是，VIG的供应不足，未来的可用性尚不确定，此外，还遇到了将人类血液产品用于治疗应用的普遍关注点。该提案旨在准备和表征针对谷谷病毒的人类单克隆抗体，该抗体可能以抗体鸡尾酒为例，将构成VIG的替代品。 我们将分离针对感染性疫苗病毒的传染性形式的中和抗体，即细胞内成熟病毒（IMV）和细胞外包膜（EEV）。 我们将特别强调隔离EEV的抗体，因为EEV介导了感染的传播，并且是针对保护性免疫反应的病毒形式。 将在体外和体内研究疫苗病毒的灭活，并将旨在设计一种抗体鸡尾酒，该抗体可在暴露前和暴露后免疫丙酰亚动物中提供防止疫苗病毒感染的保护。 设计的抗体鸡尾酒可以为天花本身提供治疗。 为了检查被动免疫在非人类灵长类动物模型中类似天花样疾病的免疫预防和免疫疗法的影响，我们将使用蒙基型病毒感染的实验模型