流行性乙型脑炎减毒活疫苗SA14-14-2E基因的稳定性

分别对SA14-14-2(PHK8代)疫苗株及其原野毒株SA14和另2个疫苗传代株SA14-14-2(PHK17代)和SA14-14-2(鼠脑1代)]的E区基因进行了序列测定.结果表明,乙脑病毒减毒活疫苗SA14-14-2在PHK细胞上连传至17代时,发现2个氨基酸突变(E-331、E-398),但不是回复突变.虽然在毒力最容易返祖的乳鼠脑内传1代后发生E-107个氨基酸回复,但与野毒株毒力相比仍然相差很大,无毒力返祖现象.在疫苗的实际质控工作中,对上述与毒力相关的基因进行监测,可能有助于发现减毒活疫苗的毒力水平,为疫苗安全性提供更可靠的检测手段.

The Stability of E Protein Gene of the Japanese Encephalitis Live Attenuated Vaccine Virus SA14-14-2

The Japanese encephalitis live attenuated virus strain SA 14 -14-2 has been used for production of live vaccine in China for ten years.However,the possibility of reverse mutation of the vaccine has not been elaborated on molecular level.In this study,we sequenced E genes of the parent wild-type strain SA 14 ,two PHK cell passaged viruses SA 14 -14-2(PHK-8),SA 14 -14-2(PHK-17),and another one ,the SA 14 -14-2(SM-1)that had been passaged once in suckling mice brain.The results indicated that there were twelve nucleotides and eight amino acids differences between SA 14 and SA 14 -14-2(PHK-8).The SA 14 -14-2(PHK-17)showed two additional mutations(E-331 and E-398)in the E protein which were not reverse mutations.Although one reverse mutation(E-107)was found in SA 14 -14-2(SM-1),its neuroattenuation was stable when tested in mice.It indicates that the genotypic characteristics of the attenuated vaccine virus SA 14 -14-2 is stable,that is consistent with the neuroattenuation stability tested in mice.