国际生物制品学杂志
國際生物製品學雜誌
국제생물제품학잡지
INTERNATIONAL JOURNAL OF BIOLOGICALS
2015年
3期
108-111
,共4页
杨会强%汪伟%刘莉娜%何婷%曾献武
楊會彊%汪偉%劉莉娜%何婷%曾獻武
양회강%왕위%류리나%하정%증헌무
日本脑炎疫苗%脑炎病毒,日本%遗传异质性
日本腦炎疫苗%腦炎病毒,日本%遺傳異質性
일본뇌염역묘%뇌염병독,일본%유전이질성
Japanese encephalitis vaccines%Encephalitis virus,Japanese%Genetic heterogeneity
目的 通过观察疫苗病毒群体中病毒个体的遗传和生物学特征,分析SA14-14-2株乙型脑炎减毒活疫苗病毒的均一性,为疫苗病毒的遗传稳定性提供实验证据. 方法 对3批疫苗病毒连续进行3次蚀斑纯化后,各挑选8个蚀斑纯化株,扩大培养一代.比较24个病毒纯化株的包膜(envelope,E)蛋白基因序列、单斑培养病毒滴度以及蚀斑特征.结果 24个纯化株中共有6个病毒株(25％)的E蛋白核苷酸发生变化,其中2株(8.3％)的核苷酸变异导致其编码氨基酸发生改变,这些变异占总核苷酸变异数的28.6％.动物实验表明,这2个纯化株没有引起小鼠神经毒力变化.在所有24个纯化株中,我国2010年版药典规定的影响疫苗病毒遗传稳定性的8个E蛋白关键位点的氨基酸均未发生改变.24个纯化株病毒的蚀斑大小和形态以及单斑培养滴度均无明显差异.结论 疫苗病毒具有典型的准种群体多样性特征,但在群体病毒中未检测到E蛋白氨基酸位点为野生型病毒位点的个体病毒,因此,疫苗病毒具有很好的减毒群体特征和遗传稳定性.
目的 通過觀察疫苗病毒群體中病毒箇體的遺傳和生物學特徵,分析SA14-14-2株乙型腦炎減毒活疫苗病毒的均一性,為疫苗病毒的遺傳穩定性提供實驗證據. 方法 對3批疫苗病毒連續進行3次蝕斑純化後,各挑選8箇蝕斑純化株,擴大培養一代.比較24箇病毒純化株的包膜(envelope,E)蛋白基因序列、單斑培養病毒滴度以及蝕斑特徵.結果 24箇純化株中共有6箇病毒株(25％)的E蛋白覈苷痠髮生變化,其中2株(8.3％)的覈苷痠變異導緻其編碼氨基痠髮生改變,這些變異佔總覈苷痠變異數的28.6％.動物實驗錶明,這2箇純化株沒有引起小鼠神經毒力變化.在所有24箇純化株中,我國2010年版藥典規定的影響疫苗病毒遺傳穩定性的8箇E蛋白關鍵位點的氨基痠均未髮生改變.24箇純化株病毒的蝕斑大小和形態以及單斑培養滴度均無明顯差異.結論 疫苗病毒具有典型的準種群體多樣性特徵,但在群體病毒中未檢測到E蛋白氨基痠位點為野生型病毒位點的箇體病毒,因此,疫苗病毒具有很好的減毒群體特徵和遺傳穩定性.
목적 통과관찰역묘병독군체중병독개체적유전화생물학특정,분석SA14-14-2주을형뇌염감독활역묘병독적균일성,위역묘병독적유전은정성제공실험증거. 방법 대3비역묘병독련속진행3차식반순화후,각도선8개식반순화주,확대배양일대.비교24개병독순화주적포막(envelope,E)단백기인서렬、단반배양병독적도이급식반특정.결과 24개순화주중공유6개병독주(25％)적E단백핵감산발생변화,기중2주(8.3％)적핵감산변이도치기편마안기산발생개변,저사변이점총핵감산변이수적28.6％.동물실험표명,저2개순화주몰유인기소서신경독력변화.재소유24개순화주중,아국2010년판약전규정적영향역묘병독유전은정성적8개E단백관건위점적안기산균미발생개변.24개순화주병독적식반대소화형태이급단반배양적도균무명현차이.결론 역묘병독구유전형적준충군체다양성특정,단재군체병독중미검측도E단백안기산위점위야생형병독위점적개체병독,인차,역묘병독구유흔호적감독군체특정화유전은정성.
Objective To analyze viral homogeneity of live attenuated Japanese encephalitis (JE) vaccine strain SA14-14-2 by investigating genetic and biological characteristics of individual virus in viral population of the vaccine,providing an experimental basis for the genetic stability of the vaccine virus.Methods Eight plaque-purified strains were selected from each of 3 lot vaccine viruses purified 3 times successively,and cultured for one passage.The gene sequences of envelope (E) protein,virus titer and plaque features were compared among the 24 strains.Results The nucleotide variation of E protein was found in 6 strains (25％),which resulted in corresponding amino acid changes in 2 strains (8.3％) and accounted for 28.6 ％ of the total nucleotide variation.The 2 strains did not enhance neurovirulence in mice.No changes were observed in 8 critical amino acid sites of E protein which influenced genetic stability as described in the current Chinese pharmacopoeia.The virus titer and plaque size and morphology were similar among the 24 strains.Conclusions The vaccine virus has quasispecies heterogeneity.No amino acid sites in E protein of wild strains are found in the viral population.The JE vaccine virus has good attenuated characteristics and genetic stability.
