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

正如我们在上一份年度报告中所指出的， 从仅来源于抗c100 -3反应性抗体的血浆池制备的IG 捐赠是在一只黑猩猩身上发起的。 输注的IG制剂， 命名为HCIG，每克IgG含有1709个PCR单位（U）的HCV RNA （平均值为495和2922单位），抗HCV滴度为 当通过多抗原EIA试剂盒（Ortho）测定时，1：1024。HCIG是 以1 g/kg bw的剂量静脉内给予黑猩猩， 也就是说，相当于接受总共3 × 104 U的HCV RNA。 以来 输注，黑猩猩既没有升高的丙氨酸转氨酶 (ALT)（等于或高于基础值的2.5倍）或 在其每周血清样本中检测到HCV RNA，持续50周。 由于抗HCV（存在于HCIG中）的滴度相对较高， 被动转移到黑猩猩体内，血清中抗-HCV呈反应性 直到第17周。 为了检测黑猩猩对HCV的易感性， 用1 ml标准HCV接种物（H血浆，103.5 CID50）。 自第53周起，HCV RNA呈阳性，而ALT呈阴性。 在第56周升高。 第54周和第56周血清中抗-HCV呈反应性 当通过EIA检测时，但当通过免疫印迹试验检测时为阴性 （RIBA-2试剂盒，Chiron）。 这项工作仍在进行中，直到黑猩猩 确认血清转化为抗-HCV阳性。 然而，尽管如此， 根据迄今为止获得的数据，黑猩猩， 容易感染HCV的患者，在接受高水平的 完全由抗c100 -3反应性抗体制备的IG制剂中的HCV RNA 捐赠 我们正在获得各方面的批准， 委员会使用更多的黑猩猩进行进一步的研究， 中和HCIG中存在的抗体。

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.