VIRAL INACTIVATION, REMOVAL, AND NEUTRALIZATION IN PLASMA DERIVATIVES

由于我们最近对一种免疫球蛋白(IG)的安全性研究 来自在黑猩猩身上进行的C100-3反应血浆池(见Z01BQ 04006-99)，我们额外获得了两只黑猩猩，用于评估 在这种浓缩的免疫球蛋白制剂中存在中和抗体 在丙型肝炎病毒抗体中。两种静脉注射免疫球蛋白制剂 使用；实验中含有高水平的丙型肝炎病毒抗体 包膜蛋白，E1和E2，而对照组几乎没有或几乎没有 抗体。实验性的HCIGIV是一种未经许可的产品 由North American Biologals，Inc.(Nabi)从血浆池中提取 来自198名抗-丙型肝炎阳性献血者的血浆，因此与我们的 之前的实验HCIG。对照免疫球蛋白IV是一种商业免疫球蛋白 产品静脉球蛋白-S，由大量捐献的血浆制备 所有这些都是由多抗原EIA筛选出来的。两种制剂都有 在制造过程中经过溶剂洗涤剂处理，没有 用我们的RT-PCR方法检测时，可检测到丙型肝炎病毒RNA。实验性的 给黑猩猩注射一种由1毫升标准物质组成的混合物 含CID_(50)的丙型肝炎病毒H株与 50毫升5%HCIGIV在4摄氏度下作用24小时，而对照组黑猩猩 将接种相同的CID50疫苗，预先培养50毫升5% 丙种球蛋白-S在相同的条件下。在8个月的输液后， 两只黑猩猩的丙氨酸转氨酶(ALT)都还没有升高 (等于或高于基本价值的2.5倍)在其每周 血清样本。这项研究仍在进行中。如果HCIGIV包含 中和丙型肝炎病毒抗体，受体黑猩猩不应该 感染丙型肝炎病毒，而对照组应该感染。

Because of our recent safety study of an Immune Globulin (IG) prepared from a c100-3 reactive plasma pool performed in a chimpanzee (see Z01 BQ 04006-99), we obtained two additional chimpanzees for assessing the presence of neutralizing antibodies in such an IG preparation enriched in antibodies to HCV. Two intravenous immunoglobulin preparations were used; the experimental contained high levels of antibodies to HCV envelope proteins, E1 and E2, while the control had little or no such antibodies. The experimental HCIGIV is an unlicensed product prepared by North American Biologicals, Inc. (NABI) from a plasma pool consisting of plasma from 198 anti-HCV positive donors and hence similar to our previous experimental HCIG. The control IGIV was a commercial IGIV product, Venoglobulin-S, which was prepared from large plasma donations all of which screened by the multiantigen EIA. Both preparations had been solvent-detergent treated in their manufacture and did not have detectable HCV RNA when assayed by our RT-PCR assay. The experimental chimpanzee was infused with a mixture consisting of 1 ml of a standard HCV inoculum (H-strain) containing 64 CID50 preincubated in vitro with 50 ml of 5% HCIGIV at 4 degrees C for 24 h while the control chimpanzee will receive the same CID50 inoculum preincubated with 50 ml of 5% Vinoglobulin-S under the same conditions. After 8 months of infusion, neither chimpanzee has yet had elevated alanine aminotransferase (ALT) (equal to or higher than 2.5 times of the basal value) in their weekly serum specimens. The study is still in progress. If HCIGIV contains neutralizing antibodies to HCV, the recipient chimpanzee should not contract HCV infection while the control should.