赵大鹏;姚为民;谷丽娟;孙丽娟;孙宇;郭雪;杨旭;陈忠强;商凤云;范宇红;王亚军;张雪梅;
ZHAO Da-peng;YAO Wei-min;GU Li-juan;SUN Li-juan;SUN Yu;GUO Xue;YANG Xu;CHEN Zhong-qiang;SHANG Feng-yun;FAN Yu-hong;WANG Ya-jun;ZHANG Xue-mei;Changchun Institute of Biological Products Co., Ltd.;

• 1:长春生物制品研究所有限责任公司

摘要(Abstract)：

目的比较相同生产工艺条件下制备的含硫柳汞和无硫柳汞流感病毒裂解疫苗的稳定性,分析硫柳汞对该疫苗稳定性的影响。方法采用WHO发布的2010/2011北半球季节性生产用推荐疫苗株,按照相同生产工艺,制备无硫柳汞(实验组)和含硫柳汞(对照组)流感病毒裂解疫苗各3批,按照企业注册标准进行成品检定,合格后,分别在2⁸℃和37℃条件下放置不同时间,进行稳定性试验。结果两组疫苗成品检测结果均符合本公司质量标准。在37℃条件下,两组疫苗的血凝素(HA)含量均有不同程度下降,保存14 d,实验组疫苗H1N1、H3N2、B型HA含量平均降幅分别为20.9%、22.2%和25.9%,对照组平均降幅分别为21.2%、22.1%和25.8%;在28℃和37℃条件下放置不同时间,进行稳定性试验。结果两组疫苗成品检测结果均符合本公司质量标准。在37℃条件下,两组疫苗的血凝素(HA)含量均有不同程度下降,保存14 d,实验组疫苗H1N1、H3N2、B型HA含量平均降幅分别为20.9%、22.2%和25.9%,对照组平均降幅分别为21.2%、22.1%和25.8%;在2⁸℃条件下,两组疫苗HA含量均缓慢下降,保存18个月,实验组疫苗H1N1、H3N2、B型HA含量平均降幅分别为15.2%、17.8%和23.1%,对照组平均降幅分别为15.3%、18.0%和23.0%;但两组疫苗HA含量均在《中国药典》三部(2010版)质量标准范围内,且同一抗原型别的HA平均降幅无明显差异。结论采用相同毒株和工艺制备的含硫柳汞和无硫柳汞流感病毒裂解疫苗,各项质量指标均符合《中国药典》三部(2010版)质量标准,取消疫苗中的硫柳汞,对流感病毒裂解疫苗的稳定性无影响。
Objective To compare the stability of thimerosal-containing and-free influenza virus split vaccines prepared under the same technological condition, and investigate the effect of thimerosal on vaccine stability. Methods Using the2010 / 2011 northern hemisphere pandemic influenza virus vaccine strains recommended by WHO, three batches of thimerosal-free(test group)and three batches of thimerosal-containing(control group) influenza virus split vaccines were prepared by the same production process, and subjected to control tests according to the standard for license. The qualified vaccines were stored at 2 8℃条件下,两组疫苗HA含量均缓慢下降,保存18个月,实验组疫苗H1N1、H3N2、B型HA含量平均降幅分别为15.2%、17.8%和23.1%,对照组平均降幅分别为15.3%、18.0%和23.0%;但两组疫苗HA含量均在《中国药典》三部(2010版)质量标准范围内,且同一抗原型别的HA平均降幅无明显差异。结论采用相同毒株和工艺制备的含硫柳汞和无硫柳汞流感病毒裂解疫苗,各项质量指标均符合《中国药典》三部(2010版)质量标准,取消疫苗中的硫柳汞,对流感病毒裂解疫苗的稳定性无影响。
Objective To compare the stability of thimerosal-containing and-free influenza virus split vaccines prepared under the same technological condition, and investigate the effect of thimerosal on vaccine stability. Methods Using the2010 / 2011 northern hemisphere pandemic influenza virus vaccine strains recommended by WHO, three batches of thimerosal-free(test group)and three batches of thimerosal-containing(control group) influenza virus split vaccines were prepared by the same production process, and subjected to control tests according to the standard for license. The qualified vaccines were stored at 2 8 and 37 ℃ for various time periods and tested for stability. Results Both the test results of vaccines in two groups met the internal quality control standard of Changchun Institute of Biological Products Co., Ltd. Both the hemagglutinin(HA)contents of vaccines in two groups decreased at 37 ℃, of which the mean decreases of types H1N1, H3N2 and B were 20. 9%, 22. 2% and 25. 9% in test group, and 21. 2%, 22. 1% and 25. 8% in control group 14 d after storage, respectively. However, the HA contents of vaccines in two groups decreased slowly at 2 8 and 37 ℃ for various time periods and tested for stability. Results Both the test results of vaccines in two groups met the internal quality control standard of Changchun Institute of Biological Products Co., Ltd. Both the hemagglutinin(HA)contents of vaccines in two groups decreased at 37 ℃, of which the mean decreases of types H1N1, H3N2 and B were 20. 9%, 22. 2% and 25. 9% in test group, and 21. 2%, 22. 1% and 25. 8% in control group 14 d after storage, respectively. However, the HA contents of vaccines in two groups decreased slowly at 2 8 ℃, of which the mean decreases of types H1N1, H3N2 and B were 15. 2%, 17. 8% and 23. 1% in test group, and 15. 3%,18. 0% and 23. 0% in control group 18 months after storage, respectively. In spite of this, both the HA contents in two groups met the requirements in Chinese Pharmaceupia(Volume Ⅲ, 2010 edition), and no significant differences were observed in the mean decreases of HA contents in the vaccines of the same types. Conclusion All the quality control indexes of thimerosal-containing and-free influenza virus vaccines prepared with the same strains by the same process met the requirements of Chinese Pharmacopoeia(Volume Ⅲ, 2010 edition). Removal of thiomersal showed no influence on the stability of influenza virus vaccine.

关键词(KeyWords)： 流感疫苗;硫柳汞;稳定性
Influenza vaccine;Thiomersal;Stability

Abstract:

Keywords:

基金项目(Foundation): 国家科技重大专项(2012ZX09201301-006);; 吉林省医药产业发展专项资金(YYZX201112);; 科技支撑计划(20130201011YY)

作者(Authors): 赵大鹏;姚为民;谷丽娟;孙丽娟;孙宇;郭雪;杨旭;陈忠强;商凤云;范宇红;王亚军;张雪梅;
ZHAO Da-peng;YAO Wei-min;GU Li-juan;SUN Li-juan;SUN Yu;GUO Xue;YANG Xu;CHEN Zhong-qiang;SHANG Feng-yun;FAN Yu-hong;WANG Ya-jun;ZHANG Xue-mei;Changchun Institute of Biological Products Co., Ltd.;

DOI: 10.13200/j.cnki.cjb.000841

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