RNA病毒在复制时有易出错的倾向,因此SARS病毒在传染或传代过程中易发生突变而产生不同的毒株,这种机制也利于病毒逃脱宿主的免疫系统而生存下来.许多研究也表明,不同的SARS病毒分离株的全基因组序列存在不同程度的差异,这些差异的研究无疑对SARS病毒疫苗的研制具有重要的指导意义.同时,对SARS病毒在传代过程中的遗传稳定性及核酸特性的分析,是SARS疫苗研制不可或缺的环节.采用PCR产物直接测序的方法,对2株用Vero细胞培养经过多次传代的SARS病毒进行了全基因组序列的测定,通过比较分析发现该病毒在传代过程中具有高遗传稳定性,其中检定参比株(Sino1株)2和11代全基因组序列比较有4个碱基的变化,而候选疫苗株(Sino3株)3与10代的基因组全序列仅有1个碱基的差异.SARS病毒在Vero细胞上传代的遗传稳定性表明,以此制备的灭活病毒疫苗是稳定的.

SARS coronavirus is an RNA virus whose replication is error-prone, which provides possibility for escape of host defenses, and even leads to evolution of new viral strains during the passage or the transmission. Lots of variations have been detected among different SARS-CoV strains. And a study on these variations is helpful for development of efficient vaccine. Moreover, the test of nucleic acid characterization and genetic stability of SARS-CoV is important in the research of inactivated vaccine. The whole genome sequences of two SARS coronavirus strains after passage in Vero cell culture were determined and were compared with those of early passages, respectively. Results showed that both SARS coronavirus strains have high genetic stability, although nearly 10 generations were passed. Four nucleotide variations were observed between the second passage and the 11th passage of Sino1 strain for identification of SARS inactivated vaccine. Moreover, only one nucleotide was different between the third passage and the 10th passage of Sino3 strain for SARS inactivated vaccine. Therefore, this study suggested it was possible to develop inactivated vaccine against SARS-CoV in the future.