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首页> 外文期刊>Current Science: A Fortnightly Journal of Research >Evaluation of the protective efficacy of a rabies DNA vaccine in mice using an intracerebral challenge model
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Evaluation of the protective efficacy of a rabies DNA vaccine in mice using an intracerebral challenge model

机译：使用脑内攻击模型评估狂犬病DNA疫苗对小鼠的保护功效

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An eukaryotic expression plasmid expressing the rabies virus surface glycoprotein (G protein) under the control of cytomegalovirus immediate early promoter and intron was constructed. This plasmid designated as pCMVRab also contains the gene conferring resistance to kanamycin (kanR) to bacteria harbouring this plasmid rather than that conferring resistance to ampicillin (ampR) and thus is devoid of the CpG immunostimulatory sequences (ISS) present in the latter. The ability of pCMVRab to induce a protective immune response was examined in outbred swiss mice using an intracerebral (i.c.) rabies virus challenge model. Following intramuscular (i.m.) inoculation, anti-G protein antibodies as well as virus neutralizing antibodies (VNA) are detected in the sera of immunized mice up to four months after immunization. Rabies virus-secific T helper cell proliferation could be demonstrated up to six months after immunization. Induction of these immune responses in pCMVRab-immunized mice results in significant protection against a subsequent lethal i.c. rabies virus challenge. Thus, we demonstrate for the first time that a rabies G protein expression plasmid devoid of the ISS present in the ampR gene confers significant protection against i.c. rabies virus challenge when inoculated into the skeletal muscle outbred swiss mice.
机译：构建了在狂犬病病毒即刻早期启动子和内含子的控制下表达狂犬病毒表面糖蛋白（G蛋白）的真核表达质粒。命名为pCMVRab的该质粒还含有赋予卡那霉素（kanR）对携带该质粒的细菌的抗性的基因，而不是赋予对氨苄青霉素（ampR）的抗性的基因，因此不含后者中存在的CpG免疫刺激序列（ISS）。使用脑内（i.c.）狂犬病病毒攻击模型检查了远交瑞士小鼠中pCMVRab诱导保护性免疫反应的能力。肌内（i.m.）接种后，直至免疫后四个月，在免疫小鼠的血清中检测到抗G蛋白抗体以及病毒中和抗体（VNA）。可以在免疫后六个月内证明狂犬病病毒特异性T辅助细胞的增殖。在经pCMVRab免疫的小鼠中诱导这些免疫反应可显着保护其免受随后的致死性i.c.狂犬病毒挑战。因此，我们首次证明了在ampR基因中不存在ISS的狂犬病G蛋白表达质粒赋予了针对i.c的显着保护。狂犬病病毒接种到骨骼肌中的瑞士杂种小鼠后受到挑战。

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