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麻疹病毒減毒过程的观察

OBSERVATIONS ON THE COURSE OF ATTENUATION OF MEASLES VIRUS

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【作者】 章以浩吳紹沅卢宝兰王子柱朱既明张守德武文煥曽国华肖俊

【Author】 CHANG I-HAO,WU SHAO-YUAN,LU PAO-LAN AND WANG TSE-CHU(National Vaccine and Serum Institute,Peking) CHU CHI-MING,CHANG SHOU-DE,WU WEN-HUAN,CHENG KUO-HUA AND HSIAO CHUN(Changchun Vaccine and Serum Institute,Changchun)

【机构】 卫生部生物制品研究所长春生物制品研究所

【摘要】 本文叙述了列4株麻疹病毒在人羊膜细胞、鸡胚羊膜腔与鸡胚细胞中的传代过程及毒力变化。观察了下列各系病毒接种易感儿后的发热反应与血凝抑制抗体。一、在人羊膜细胞中传代的"羊膜系"(HAM)其毒力较自然麻疹已显著减轻,但从45代到69代之间继续传代,进一步的减毒作用不显著。二、在鸡胚中传代减毒作用很明显。以羊膜系病毒适应于鸡胚而获得了"鸡胚系"(CE),第12代时毒力无变化,在12代与20代之间,反应性与抗体水平呈急剧下降,但至33代抗体水平与抗体阳转率仍然维持在20代的水平,未继续下降。于鸡胚中传18代后改用快速传代法(每4—6天传代,以代替原来的9天传代),病毒繁殖高峰提前,由此而获得了"鸡胚快传系"(CER)。该系毒种的反应性也极低,但虽经快传至18代(合计在鸡胚中共传36代),仍保留了较高的阳转率及相当的抗体水平,与CE20无大区别。三、羊膜病毒直接适应于鸡胚细胞后出现了三种不同情况:1)HAM60CEC系虽然在鸡胚细胞中传至14代,但始终未能适应在该系统中繁殖,减毒作用也不显著;2)HAM47 CEC系的发热反应已明显降低,但仍不稳定,其免疫性与羊膜系相近;3)HAM55 CEC系的发热反应极度降低,抗体阳转率仍高,但抗体水平则显著下降。从以上结果看来,似乎麻疹病毒在鸡胚细胞中传代可出现不同程度的减毒。四、通过鸡胚后再适应于鸡胚细胞的三系毒种CE15 CEC、CER8ECEC和CE26 CEC均能达到高度减毒,但免疫性似有一定损失,其极端者如CE26,CEC不但抗体水平很低,阳转率也显著下降。根据以上结果,对麻疹病毒减毒的规律性提出了讨论;病毒可依其毒力水平分为强毒、初步减毒株、中等度减毒株、高度减毒株及超减毒株。在人羊膜细胞、鸡胚或鸡胚细胞中传代均有减毒效果。减毒在一定代数后出现,但在某一系统中传递的代数并不是直接决定减毒程度的唯一因素。病毒在某一系统中传代,毒力减弱到一定程度后,继续传代的减毒作用就不明显,而在更换另一系统传代后,就可能出现进一步的减毒。

【Abstract】 This paper describes the variation in virulenceof the Leningrad 4 Strain of measles virus in thecourse of passage in human amnion cells,chickembryos and chick embryonic cells.The febrilereaction and hemagglutination-inhibition antibodyof serum negative children inoculated with the vari-ous virus lines were observed: 1. The febrile reaction caused by the humanamnion line(HAM)was already much milder thanthat of natural measles,but in the course of passagefrom 45 to 69 generations,no further attenuationwas observed. 2. Passage in the amniotic cavity of chickembryos resulted in a marked attenuating effect.The chick embryo line(CE)still preserved its ori-ginal virulence at the 12th passage,but rapid re-duction in febrile reaction and antibody leveloccurred between the 12th and 20th passages.Further passages up to the thirtythird,however,did not cause appreciable further changes. Starting from CE18,a"Rapid passage line"(CER)was established by passing every4—6instead of the original 9 days.This line causedvery little febrile reaction,but retained the capacityof inducing moderate antibody response and ahigh conversion rate even after 18 rapid passages(a total of 36 chick embryo passages). 3. The three lines obtained by adapting hu-man amnion virus directly to chick embryonic cellsdiffered considerably in their behaviour.HAM60CECwhich was not well adapted even after 14 passagesin chick embryonic cells, appeared to be as reacto-genic as the original HAM line. HAM47CECcaused reduced febrile reaction and retained goodimmunogenicity,but appeared to be unstable.HAM55,CEC induced very little febrile reaction andgood antibody conversion rate,but the antibodylevel of inoculated subjects was appreciably lowered.It seems,therefore,that different degrees of attenua-tion may be obtained after chick embryonic cellpassages. 4. nother three lines were obtained by adap-tation to chick embryonic cells after preliminarypassages in chick embryos.These three lines,namely,CE15CEC,CER8ECEC and CE26CEC allcaused little febrile reaction,but further loss ofimmunogenicity seemed to have occurred.In theextreme case of CE26CEC,not only the antibodylevel,but the conversion rate was markedly lowered.Basing on the above results,several rules go-verning the attenuation of measles virus were sug-gested:Measles virus may be classified into vir-ulent,slightly attenuated,moderately attenuated,highly attenuated and over-attenuated according totheir virulence levels.Passages in human amnioncells,chick embryos and chick embryonic cells allexhibited attenuating effect.Attenuation only ap-peared after a certain number of passages,but thenumber of passages in a given system was not thesole factor determining the degree of attenuation.When the virulence had been reduced to a certainlevel after a number of passages in a given system,it remained relatively stable thereafter on furtherpassage.Further attenuation,however,may beachieved by additional passages in another system.

  • 【文献出处】 微生物学报 ,Acta Microbiologica Sinica , 编辑部邮箱 ,1966年01期
  • 【被引频次】5
  • 【下载频次】45
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