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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DEVELOPMENT OF A SAFE LIVE LEISHMANIA VACCINE LINE BY GENE REPLACEMENT
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DEVELOPMENT OF A SAFE LIVE LEISHMANIA VACCINE LINE BY GENE REPLACEMENT

机译：基因替代开发安全的利什曼原虫活疫苗生产线

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Vaccination with live Leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines, To circumvent this, we tested the ability of a dhfr-ts(-) null mutant of L. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent L. major. Survival and replication of dhfr-ts(-) in macrophages in vitro were dependent upon thymidine, with parasites differentiating into amastigotes prior to destruction, dhfr-ts(-) parasites persisted in BALB/c mice for up to 2 months, declining with a half-life of 2-3 days, Nonetheless, dhfr-ts(-) was incapable of causing disease in both susceptible and immunodeficient (nuu) BALB/c mice, Animal infectivity could be partially restored by thymidine supplementation. When inoculated by the i.v., s.c., or i.m. routes into mice, dhfr-ts(-) could elicit substantial resistance to a subsequent challenge with virulent L. major. Thus, Leishmania bearing auxotrophic gene knock-outs can be safe and induce protective immunity, Potentially, dhfr-ts(-) could be used as a platform for delivery of immunogens relevant to other diseases. [References: 42]
机译：已经证明，用活的利什曼原虫进行活疫苗可以在人类中产生有效的免疫。但是，由于与可用疫苗系的毒力相关的问题，该疫苗已被中止。为避免这种情况，我们测试了通过基因靶向获得的大链球菌dhfr-ts（-）null突变体感染然后感染的能力。接种小鼠以抵抗强毒大肠埃希氏菌的攻击。 dhfr-ts（-）在体外巨噬细胞中的存活和复制取决于胸腺嘧啶，寄生虫在被破坏之前会分化成变形虫，而dhfr-ts（-）寄生虫在BALB / c小鼠中可持续长达2个月，随着半衰期为2-3天，尽管如此，dhfr-ts（-）不能在易感和免疫缺陷（nu / nu）BALB / c小鼠中引起疾病​​。补充胸苷可部分恢复动物的传染性。由静脉注射，皮下注射或肠衣接种。在进入小鼠体内的途径后，dhfr-ts（-）可能引起对强毒大肠埃希氏菌随后攻击的实质性抵抗。因此，利什曼原虫携带营养缺陷型基因敲除可以安全并诱导保护性免疫。潜在地，dhfr-ts（-）可以用作递送与其他疾病相关的免疫原的平台。 [参考：42]

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