2010年中国人免疫球蛋白中EV71中和抗体效价的比较研究

目的: 了解2010年我国生产的静注人免疫球蛋白(IVIG)中抗-EV71中和抗体效价的情况,为治疗EV71引起的手足口病(HFMD)提供特异性治疗药物。 方法: 采用经典微量细胞病变法,应用近2年分离自中国大陆的2株肠道病毒71型(EV71)病毒株,对我国不同血液制品厂家生产的97批IVIG进行抗-EV71中和效价检测,比较不同批次IVIG的EV71中和效价。 结果: 19家生产企业生产的97批IVIG的EV71中和效价几何平均滴度(GMTs)为1∶ 180(1∶ 170~1∶ 191)。其中有7家生产企业生产的12批制品的中和效价大于1∶ 256,以S公司生产的20100406批制品效价最高为1∶ 543,以A公司生产的含有1∶ 256以上效价的IVIG批数最多(5批),使该公司生产的IVIG的平均EV71中和抗体效价显著高于其他10家企业(P<0.05)。进一步分析显示,该2个公司分别是通过对献血员的EV71中和效价进行筛选,挑选出高效价血浆和选择人群抗体水平较高地区作为血浆来源地进行投料,而制备出了含有高效价EV71中和抗体的IVIG。 结论: 本研究显示,生产企业只要对原料血浆进行合理控制,制备出含有高效价EV71中和抗体的IVIG是可行的。

Objective: To explore the anti-EV71 titer in human immunoglobulins produced by different blood product manufacturers in China in 2010.To provide specific drugs for hand,foot and mouth disease(HFMD) caused by EV71. Methods: 97 Lots of human immunoglobulins for intravenous injection (IVIG) produced by different manufacturers were tested for neutralizing antibodies (NTAb) to EV71 by microneutralization test with 2 different EV71 viruses,which isolated from mainland china in the past two years.The difference of anti-EV71 titer in IVIG has been compared. Results: The geometric mean titers (GMTs) of EV71 NTAb in 97 Lots IVIG is 1∶ 180 (1∶ 170-1∶ 191).The titers of EV71 NTAb in 12 Lots IVIG produced by 7 different manufacturers have been more than 1∶ 256,and the IVIG of Lot 20100406 produced by S manufacturer has the highest titer (1∶ 543).The A manufacturer had made the most Lot of IVIG (5 batches) with anti-EV71 titer higher than 1∶ 512,that made the average of anti-EV71 from A manufacturer to be obviously higher than other 10 manufacturers (P<0.05).Further analysis revealed that S manufacturer had tested the anti-EV71 titers in plasma of raw materials and selected the plasma with high titer of EV71 to produce this Lot IVIG;and A manufacturer selected the areas with high anti-EV71 levels in populations as a plasma source to feed and make IVIGs. Conclusion: This study shows that through controlling the neutralizing antibodies levels to EV71 of raw materials efficiently by the manufacturer,it is scientific and feasible to produce IVIG with high anti-EV71 titer.