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: 3748299
• 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/3748299
• 关键词: Pan; alanine transaminase; antibody titering; antiviral antibody; drug quality /standard; drug screening /evaluation; enzyme linked immunosorbent assay; hepatitis C virus; human tissue; immunoglobulin G; immunological substance; neutralizing antibody; passive immunization; polymerase chain reaction; serum globulins; virus RNA

As indicated in our previous annual report, an infectivity study of an IG prepared from a plasma pool derived solely from anti-c100-3 reactive donations was initiated in a chimpanzee. The infused IG preparation, designated as HCIG, contained 1709 PCR units (U) of HCV RNA per g of IgG (average value of 495 and 2922 units), and had an anti-HCV titer of 1:1024 when assayed by a multiantigen EIA kit (Ortho). The HCIG was administered intravenously to a chimpanzee at a dosage of 1 g/kg bw, i.e., equivalent to receiving a total of 3 x 104 U of HCV RNA. Since the infusion, the chimpanzee had neither elevated alanine aminotransferase (ALT) (equal to or higher than 2.5 times of the basal value) nor detectable HCV RNA in its weekly serum sample for a period of 50 weeks. Because of the relatively high titer of anti-HCV (present in HCIG) passively transferred to the chimpanzee, anti-HCV in sera was reactive until week 17. To check the susceptibility of the chimpanzee with HCV, it was challenged with 1 ml of a standard HCV inoculum (H plasma, 103.5 CID50) at week 51. HCV RNA was positive since week 53 while ALT was elevated at week 56. Anti-HCV was reactive in sera at weeks 54 and 56 when tested by EIA but was negative when tested by an immunoblot assay (RIBA-2 kit, Chiron). The work is still in progress until the chimpanzee is confirmed to be seroconverted to anti-HCV positive. Nevertheless, based upon the data obtained thus far, the chimpanzee, which was susceptible to HCV infection, was safe when it received a high level of HCV RNA in an IG preparation made entirely from anti-c100-3 reactive donations. We are in the process of obtaining approvals from various committees to use additional chimpanzees for further studies on possible neutralized antibodies present in HCIG.

正如我们在上一份年度报告中所指出的，对一种 从仅由抗C100-3反应产生的血浆池制备的IG 捐赠是在一只黑猩猩身上发起的。注入的免疫球蛋白制剂， 命名为HCIG，每克IgG含有1709个聚合酶链式反应单位(U)的丙型肝炎病毒RNA (平均值为495和2922个单位)，抗丙型肝炎病毒滴度为 用多抗原EIA试剂盒(ORTHO)检测时为1：1024。HCIG是 给黑猩猩静脉注射剂量为1g/kg bw， 即相当于总共收到3x104U的丙型肝炎病毒RNA。自.以来 注射后，黑猩猩的丙氨酸转氨酶既没有升高 (ALT)(等于或高于基本值的2.5倍)或 在为期50周的每周血清样本中检测到丙型肝炎病毒RNA。 由于抗-丙型肝炎病毒滴度相对较高(存在于丙型肝炎免疫球蛋白中) 被动转移给黑猩猩，血清中抗-丙型肝炎病毒呈反应性 直到第17周。为了检查黑猩猩对丙型肝炎病毒的易感性， 用1毫升标准丙型肝炎疫苗(H血浆，103.5)攻击它 CID50)在51周。丙型肝炎病毒RNA自53周起呈阳性，而丙氨酸转氨酶 在56周时升高。54周和56周血清中抗-丙型肝炎病毒呈阳性反应 经EIA检测，但免疫印迹检测为阴性 (RIBA-2试剂盒，CHIRON)。这项工作仍在进行中，直到黑猩猩 已确认血清转换为抗-丙型肝炎病毒阳性。不过， 根据目前获得的数据，黑猩猩，这是 易受丙型肝炎病毒感染，在接受高水平的 完全由抗C100-3反应性抗体制成的免疫球蛋白中的丙型肝炎病毒RNA 捐款。我们正在获得各方面的批准 委员会将使用更多黑猩猩进一步研究可能的 HCIG中存在中和抗体。