Enriched IVIG for the treatment of West Nile Virus

用于治疗西尼罗病毒的浓缩 IVIG

• 批准号: 6818232
• 负责人: Israel K Nur
• 金额: $ 100万
• 依托单位: OMRIX BIOPHARMACEUTICALS, LTD
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6818232
• 关键词: West Nile virus; antibody neutralization test; arthropod borne communicable disease; biotechnology; cooperative study; emerging infectious disease; enzyme linked immunosorbent assay; hamsters; high throughput technology; human subject; immunoglobulin G; immunotherapy; laboratory mouse; laboratory rat; serotyping; vaccine development; viral vaccines

DESCRIPTION (provided by applicant): Long-term Objectives: To develop a high-titer anti-West Nile virus immune globulin preparation (WNIG) as an effective first line countermeasure to West Nile Virus (WNV) infections. On completion of this project we expect to be ready to commence the testing of WNIG in humans. Israeli plasma will be screened and plasma with antibodies to WNV will be collected. Since WNV is endemic in Israel and non-specific Israeli IVlG has already been used with some success in treating infected patients, the resulting WNIG is expected to contain high-titer WNV immunoglobulins and may be used as an emergency prophylactic as well as an effective treatment. Later in the project WNIG will be developed from American plasma. Specific Aim #1: Develop enriched WNIG by screening and selection for IgG positive plasma, fractionation and characterization: WNIG will be derived from Israeli plasma donations testing positive by ELISA for WNV IgG. The result will be at least 10 times more potent than the preparation (Omr-lgG-am) currently used in an NIH clinical study and emergency cases. Specific Aim #2: Test the efficacy of the enriched WNIG and achieve supportive clinical information for various routes of infection: In-vivo models will test increased potency. Initial animal tests will be in mosquito transmission of WN encephalomyelitis. Other routes of infection will include transplantation and breast-feeding. Specific Aim #3: Improve the screening method for the selection of convalescence (or vaccinated) plasma donors that have high titers of neutralization antibodies: Preliminary research indicates that some samples exhibit high binding and low neutralization (and vice versa). Short recombinant peptides will be used to isolate antibodies that bind to specific sites resulting in virus neutralization. This will enable high throughput ELISA to be used to select plasma donations with specific binding to high neutralization sites. Specific Aim #4: Identify US subjects with WNV antibodies, select plasma donors and develop a US plasma-derived enriched WNIG: Approaches used in Specific Aims #1-3 will be used to develop a US plasma-derived WNIG. In the absence of sufficient WN antibodies in convalescent donors, hyper-immune donors treated with an attenuated vaccine may be explored as an alternative source of plasma.

描述（由申请人提供）： 长期目标：开发高滴度抗西尼罗河病毒免疫球蛋白制剂（WNIG），作为西尼罗河病毒（WNV）感染的有效一线对策。该项目完成后，我们预计将准备好开始 WNIG 的人体测试。将对以色列血浆进行筛查，并收集含有西尼罗河病毒抗体的血浆。由于西尼罗河病毒在以色列流行，并且非特异性以色列 IVIG 已在治疗感染患者方面取得了一些成功，因此由此产生的 WNIG 预计将含有高滴度的西尼罗河病毒免疫球蛋白，可用作紧急预防和有效治疗。项目后期的 WNIG 将从美国等离子体中开发出来。具体目标#1：通过筛选和选择 IgG 阳性血浆、分级分离和表征来开发富集 WNIG：WNIG 将源自以色列捐献的血浆，经 ELISA 检测为 WNV IgG 呈阳性。结果将比目前在 NIH 临床研究和紧急情况下使用的制剂 (Omr-IgG-am) 有效至少 10 倍。具体目标#2：测试富集 WNIG 的功效并获得各种感染途径的支持性临床信息：体内模型将测试增强的效力。最初的动物试验将针对蚊子传播 WN 脑脊髓炎。其他感染途径包括移植和母乳喂养。具体目标#3：改进筛选方法，以选择具有高滴度中和抗体的恢复期（或已接种疫苗）血浆供体：初步研究表明，一些样品表现出高结合和低中和（反之亦然）。短重组肽将用于分离与特定位点结合从而中和病毒的抗体。这将使高通量 ELISA 能够用于选择与高中和位点特异性结合的血浆捐赠。具体目标#4：识别具有 WNV 抗体的美国受试者，选择血浆供体并开发美国血浆衍生的富集 WNIG：具体目标#1-3 中使用的方法将用于开发美国血浆衍生的 WNIG。在恢复期供体中缺乏足够的 WN 抗体的情况下，可以探索用减毒疫苗治疗的超免疫供体作为血浆的替代来源。