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目的分析麻疹减毒活疫苗S191生产用毒株病毒结构基因的遗传稳定性。方法将北京天坛生物制品股份有限公司(天坛生物)用于麻疹疫苗生产的S191株25代病毒(S191-BJ25)传至29代(S191-BJ29),上海生物制品研究所保存的S191株24代病毒(S191-SH24)传至33代(S191-SH33)。从S191株传代病毒中提取RNA,对病毒结构基因片段N、M、F、H进行扩增及测序。将测序结果与GenBank中1994年收录的S191株麻疹病毒的相应序列进行比较分析。结果S191-BJ25传代病毒N、M、F、H4个基因的总突变率为0.02%,S191-SH24传代病毒为0.15%;与1994年的S191疫苗株相比,S191-BJ25传代病毒N、M、F、H4个基因的总突变率为0.3%,S191-SH24传代病毒为0.4%。结论目前天坛生物使用的麻疹疫苗S191株生产用三级种子库具有可靠的遗传稳定性,从主代种子到疫苗的传代过程中,N、M、F、H结构基因表现出稳定的分子遗传特征。目前使用的S191毒株的4个结构基因较1994年以前的疫苗株发生了变化,但目前没有证据表明这些变化对免疫原性产生不利影响。
Objective To analyze the genetic stability of the virus structural gene of live attenuated vaccine strain S191. Methods S191 strain 25 (S191-BJ25) virus of measles vaccine production was transferred to 29 generations (S191-BJ29) of Beijing Tiantan Biological Products Co., Ltd. (Tiantan Biological Products Co., Ltd.), S191 strain of 24 generations maintained by Shanghai Institute of Biological Products The virus (S191-SH24) spread to passage 33 (S191-SH33). RNA was extracted from the S191 strain of virus and the viral structural gene fragments N, M, F and H were amplified and sequenced. The sequencing results were compared with the corresponding sequences of S191 measles virus collected in GenBank in 1994. Results The total mutation rates of N, M, F and H genes of S191-BJ25 were 0.02% and 0.15% for S191-SH24, respectively. Compared with the S191 vaccine strain of 1994, the S191-BJ25 germline viruses contained N, M The total mutation rates of F and H genes were 0.3% and 0.4% for S191-SH24. Conclusion At present, the third-grade seed bank of measles vaccine S191 used in Tiantan Biological Station has reliable genetic stability. The N, M, F and H structural genes show stable molecular genetic characteristics during passage from the main seed to the vaccine . The 4 structural genes of the S191 strain currently in use have changed as compared to the vaccine strains prior to 1994, but there is currently no evidence that these changes have an adverse effect on immunogenicity.