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目的考察毕赤酵母表达的含前S抗原重组乙型肝炎疫苗原液和成品的稳定性。方法将3批疫苗原液置4℃存放,分别于0、1、2、3、6个月时取样,测定其在各时间点的乙型肝炎表面抗原S、前S1(PreS1)、前S2(PreS2)抗原滴度及HPLC纯度;将3批疫苗成品置25℃和4℃存放,进行加速稳定性和长期稳定性试验,分别于0、1、2、3、6个月和0、3、6、9、12、18、24个月时取样,进行小鼠效力、pH值、细菌内毒素和无菌测定。结果 3批疫苗原液于4℃保存6个月,表面抗原S、PreS1、PreS2抗原滴度及HPLC纯度均无明显变化;3批疫苗成品于25℃放置6个月和4℃放置24个月,各个时间点的小鼠效力均符合暂定规程的要求,pH值保持稳定,细菌内毒素和无菌试验均符合《中国药典》三部(2005和2010版)要求。结论毕赤酵母表达的含前S抗原重组乙型肝炎疫苗原液及成品稳定性良好。
Objective To investigate the stability of recombinant hepatitis B vaccine containing recombinant S antigen expressed in Pichia pastoris and its finished product. Methods The three batches of vaccine stock solution were stored at 4 ℃. Samples were taken at 0, 1, 2, 3 and 6 months respectively. The levels of hepatitis B surface antigen S, PreS1, PreS2) antigen titer and HPLC purity. The three batches of vaccine products were stored at 25 ° C and 4 ° C for accelerated stability and long-term stability test at 0, 1, 2, 3, 6 months and 0, Samples were taken at 6, 9, 12, 18 and 24 months for mouse efficacy, pH, bacterial endotoxin, and sterility assays. Results The three batches of vaccine stock solution were stored at 4 ℃ for 6 months. No significant changes were observed in the surface antigen S, PreS1, PreS2 antigen titers and HPLC purity. The three batches of vaccine products were placed at 25 ℃ for 6 months and 4 ℃ for 24 months, The efficacy of mice at all time points was in accordance with the requirements of the tentative regulations, the pH value remained stable, bacterial endotoxin and sterility tests were in line with the “Chinese Pharmacopoeia” three (2005 and 2010 version) requirements. Conclusions The recombinant hepatitis B vaccine containing the pre-S antigen expressed by Pichia pastoris and its stability are good.