低pH孵放对免疫抑制剂抗人T细胞猪免疫球蛋白病毒灭活效果的验证

Validation of virus inactivation effect of low pH incubation process for immunosuppressants anti-human T lymphocyte porcine immunoglobulin

目的通过对免疫抑制剂抗人T细胞猪免疫球蛋白(anti-human T lymphocyte porcine immunoglobulin,P-ATG)低pH孵放工艺[pH 3.8~4.2,(24±2)℃,24 d]病毒灭活效果的验证,评价动物源性多抗免疫抑制剂的安全性。方法以人源的水疱性口炎病毒(vesicular stomatitis virus,VSV)、辛德毕斯病毒(Sindbis virus,SV)和猪源的伪狂犬病毒(pseudorabies virus,PRV)以及人免疫缺陷病毒(human immunodeficiency virus,HIV)作为指示病毒,检测低pH孵放工艺对这些包膜病毒的灭活效果。结果P-ATG经低pH孵放[pH 3.8~4.2,(24±2)℃,24 d]后,指示病毒VSV、SV、PRV和HIV的滴度分别下降了5.75~6.00 lgTCID_(50)/0.1 mL,6.70~6.98 lgPFU/mL,5.25~5.75 lgTCID_(50)/0.1 mL和4.20~4.40 lgTCID_(50)/mL,下降滴度均在4.0 lg以上。结论P-ATG低pH孵放工艺能有效灭活4个lg以上的包膜病毒,保证人用免疫抑制治疗制剂P-ATG的用药安全。

Objective To evaluate the safety of animal-derived poly-anti-immunosuppressants by validating the effect of low pH incubation process[pH 3.8-4.2,(24±2)℃,24 d]of the immunosuppressant anti-human T lymphocyte porcine immunoglobulin(P-ATG)on virus inactivation.Methods The inactivation efficacy of enveloped viruses in low pH incubation process was evaluated using human-originated vesicular stomatitis virus(VSV),Sindbis virus(SV),swine-originated pseudorabies virus(PRV),and human immunodeficiency virus(HIV)as indicators.Results After incubation with P-ATG at low pH[pH 3.8-4.2,(24±2)℃,24 d],the titers of the four indicator viruses VSV,SV,PRV and HIV decreased by 5.75-6.00 lgTCID_(50)/0.1 mL,6.70-6.98 lgPFU/mL,5.25-5.75 lgTCID_(50)/0.1 mL and 4.20-4.40 lgTCID_(50)/mL,all with decreasing titers of 4.0 lg or more.Conclusion The low pH incubationis process of P-ATG can effectively inactivate the enveloped virus and ensure the safety of administration of P-ATG,a human immunosuppressive therapeutic agent.