Enriched IVIG for the treatment of West Nile Virus

描述（由申请人提供）：长期目标：开发高滴度抗西尼罗病毒免疫球蛋白制剂（WNIG），作为西尼罗病毒（WNV）感染的有效一线对策。该项目完成后，我们预计将准备开始在人体中进行WNIG测试。将对以色列人的血浆进行筛查，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，非特异性的以色列IVlG已经在治疗感染患者方面取得了一些成功，因此预计所得的WNIG含有高滴度的西尼罗河病毒免疫球蛋白，可能被用作紧急预防和有效治疗。在项目的后期，WNIG将从美国的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，分离和表征来开发富集的WNIG: WNIG将来自经ELISA检测为WNV IgG阳性的以色列血浆捐献。结果将比目前在NIH临床研究和急诊病例中使用的制剂（omr - gg -am）的效力至少高10倍。具体目标2：测试增强的WNIG的功效，并获得对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。最初的动物试验将是蚊子传播西尼罗脑脊髓炎。其他感染途径包括移植和母乳喂养。具体目标#3：改进筛选具有高滴度中和抗体的恢复期（或接种过疫苗）血浆供者的方法：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的抗体，从而使病毒中和。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供体。特异性目标#4：确定美国受试者的WNV抗体，选择血浆供体并开发美国血浆来源的富集WNIG：特异性目标#1-3中使用的方法将用于开发美国血浆来源的WNIG。在恢复期供者缺乏足够的抗体的情况下，可以探索用减毒疫苗治疗的超免疫供者作为血浆的替代来源。

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.