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：开发高细胞抗西尼罗河病毒免疫球蛋白制剂（WNIG）作为对西尼罗河病毒（WNV）感染的有效第一线对策。该项目完成后，我们希望准备开始对人类的WNIG进行测试。将筛选以色列血浆，并收集具有抗WNV抗体的等离子体。由于WNV在以色列中是地方性的，并且非特异性以色列IVLG已经成功地治疗感染患者，因此预计所得的WNIG有望含有高敏化WNV免疫球蛋白，可以用作紧急预防性的预防性预防症和有效治疗。在该项目的后期，WNIG将从美国等离子体开发。特定目标＃1：通过筛选和选择IgG阳性等离子体，分馏和表征来发展富集的WNIG：WNIG将来自以色列血浆捐赠测试，ELISA阳性WNV IgG。结果将比当前在NIH临床研究和紧急病例中使用的制剂（OMR-LGG-AM）的效力至少要高10倍。具体目的＃2：测试富集的WNIG的功效并为各种感染途径获得支持性的临床信息：体内模型将测试增加的效力。最初的动物测试将是WN脑脊髓炎的蚊子传播。其他感染途径将包括移植和母乳喂养。特定目的＃3：改进选择具有高剂量中和抗体的康复（或接种疫苗）血浆供体的筛选方法：初步研究表明，某些样品表现出高结合和低中和（以及vice festa）。短重组肽将用于分离与特定位点结合的抗体，从而导致病毒中和。这将使高吞吐量ELISA用于选择具有特异性结合高中和位点的血浆捐赠。特定目的＃4：确定具有WNV抗体，选择等离子体供体的美国受试者，并开发美国等离子体衍生的富含WNIG：使用特定目标＃1-3中使用的方法将用于开发美国等离子体衍生的WNIG。在康复供体中没有足够的WN抗体的情况下，可以探索用衰减疫苗处理的高免疫供体作为血浆的替代来源。