SAFETY STUDY OF AN IMMUNE GLOBULIN PREPARED FROM A C100-3 REACTIVE PLASMA POOL

由 C100-3 反应血浆库制备的免疫球蛋白的安全性研究

• 批准号: 3770451
• 负责人: M W YU
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3770451
• 关键词: Pan; alanine transaminase; animal viral hepatitis; antibody titering; antiviral antibody; drug administration rate /duration; drug screening /evaluation; enzyme linked immunosorbent assay; hepatitis C virus; human tissue; immunoglobulin G; immunological substance; passive immunization; polymerase chain reaction; serum globulins; virus RNA

Because of concern that immune globulins (IG) containing HCV RNA may transmit hepatitis C, the infectivity of an IG prepared from a plasma pool derived solely from anti-c100-3 reactive donations was determined in a chimpanzee. The chimpanzee is the only known animal model for evaluation of HCV infection. This IG preparation, designated as HCIG, was a 5.2% protein solution, contained 250 PCR units/g IgG, and had an anti-HCV titer of 1:1024 when assayed by multiantigen EIA kit (Ortho). The HCIG was administered intravenously to a chimpanzee at a dosage of 500 mg IgG/kg bw per day for two consecutive days (total dose, 1 g/kg, equivalent to a rather large human dosage). The chimpanzee has been bled weekly and liver biopsied triweekly. Thus far, 3 months after infusion, alanine aminotransferase (ALT) levels remain in the normal range and HCV RNA has not been detected. The follow-up period for infectious markers (i.e., ALT and HCV RNA) will be 12 months; HCIG would be considered noninfectious if both parameters remain negative for that period and the chimpanzee is subsequently shown to be susceptible to HCV infection after challenge with a known infectious inoculum. The outcome of this study is of paramount importance in defining the infectivity of IG (and perhaps of other plasma derivatives) that contain HCV RNA, and may serve as a basis for further studies on possible protective antibodies in HCIG.

由于担心含有HCV RNA的免疫球蛋白（IG）可能 传播丙型肝炎，从血浆池制备的IG的传染性 仅来源于抗c100 -3反应性捐赠者， 黑猩猩 黑猩猩是唯一已知的用于评估的动物模型 HCV感染。 这种IG制剂，命名为HCIG，是5.2%的 蛋白质溶液，含有250个PCR单位/g IgG，并且具有抗HCV滴度 当用多抗原EIA试剂盒（Ortho）测定时，为1：1024。 HCIG是 以500 mg IgG/kg bw的剂量静脉内给予黑猩猩 每天连续两天（总剂量，1 g/kg，相当于 相当大的人体剂量）。 这只黑猩猩每周都被流血的， 每三周进行一次活检。 到目前为止，输注后3个月，丙氨酸 转氨酶（ALT）水平保持在正常范围内，HCV RNA 未被检测到。 感染标志物的随访期（即，ALT 和HCV RNA）将为12个月; HCIG将被视为非感染性， 这两个参数在这段时间内都是负值， 随后显示在用以下物质攻击后对HCV感染易感 一种已知的传染性接种物 这项研究的结果至关重要， 重要的是确定感染性的IG（也许其他血浆 含有HCV RNA的衍生物），并可作为进一步研究的基础。 研究HCIG中可能的保护性抗体。