聚乙二醇化重组集成α干扰素在食蟹猴长期毒性中结合抗体和中和抗体的活性

Activities of Serum Binding Antibody and Neutralizing Antibody on the Cynomolgus Undergoing Long-term Toxicity Study with Polyglycol Recombinant Consensus Interferon α

研究了食蟹猴皮下注射聚乙二醇化重组集成α干扰素(代号PEG-SA)低、中、高剂量(10,30,90μg/kg及对照组)1次/7 d,共180 d后血清中第15,29,43,57,71,92,113,134,162,180 d及停药后30 d的结合抗体及中和抗体滴度。结合抗体测定采用的是间接ELISA法,中和抗体测定采用的是细胞病变抑制法。结合抗体滴度以OD值大于阴性对照组OD值2.1倍为阳性。中和抗体活性的产生以保护50%细胞免受病毒侵犯为判断依据,即50%细胞病变表明产生中和抗体。结果表明,两者活性均在57 d到达高峰,停药后结合抗体和中和抗体活性减弱或消失,中高剂量组抗体活性高于同时段低剂量组活性。PEG-SA皮下注射后,可诱导食蟹猴产生结合抗体及中和抗体,二者活性具有剂量相关性。

To study the titer of binding antibody and neutralizing antibody about m.fascicularis＇ serum after subcutaneous injected 1/7d,a total of 180 days with low,middile and high-dose（10ug/kg,30ug/kg,90ug/kg and control group）pegylated of recombinant interferon alfacon（codenamed PEG-SA） for 15th,29th,43th,57th,71th,92th,113th,134th,162th and 180th and 30th after drug withdrawal.Methods：Binding antibody was measured by the indirect ELISA.Neutralizing antibody was measured by the cytopathic effect inhibition assay.Judgments based on：binding antibody titers with OD values greater than the negative control group＇s 2.1 times as positive.Production of neutralizing antibody activity of protect 50% cells from virus encroachment as a judgment.50% cells has pathological change provided produce neutralizing antibody.Result：On the 57th,both binding antibody and neutralizing antibody of activity reach the peak,and their to diminish or disappear after withdrawal.Antibody activity in the middle and high-dose group is higher than the low-dose group at the same time.Conclusion： Subcutaneous injection with PEG-SA,may induce m.fascicularis produced binding antibody and neutralizing antibody,both titer of them has dose-dependent.