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首页> 外文期刊>Infection and immunity >A recombinant minigene vaccine containing a nonameric cytotoxic-T-lymphocyte epitope confers limited protection against Listeria monocytogenes infection.
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A recombinant minigene vaccine containing a nonameric cytotoxic-T-lymphocyte epitope confers limited protection against Listeria monocytogenes infection.

机译：含有小分子细胞毒性T淋巴细胞表位的重组小基因疫苗可针对单核细胞增生李斯特菌感染提供有限的保护。

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We have previously shown that vaccines expressing virus-derived cytotoxic-T-lymphocyte (CTL) epitopes as short minigenes can confer effective protection against virus challenges, and here we extend these studies to the bacterium Listeria monocytogenes. Host defense against this important human pathogen appears largely T cell mediated, and a nonamer CTL epitope from the listeriolysin O (LLO) protein has been identified in BALB/c mice. We have synthesized this nonamer as a minigene, expressed it in a recombinant vaccinia virus (VV-list), and used this to immunize mice. Memory CTLs cultured from VV-list-immunized mice specifically lyse target cells pulsed with a nonamer peptide identified at LLO amino acid residues 91 to 99. Four weeks postimmunization, mice were challenged with L. monocytogenes. By day 6 following challenge with a sublethal dose of L. monocytogenes, mice immunized with VV-list showed a approximately 2,000- to 6,000-fold reduction in bacteria CFU in the spleen and liver. At this time point, with control mice, bacterial were readily detectable by Gram stain of the liver but were undetectable in the VV-list-immunized animals. Additionally, when a normally lethal dose of bacteria was given, death was delayed in VV-list-immunized animals. This study has demonstrated that a single immunization with a recombinant vaccinia virus bearing only nine amino acids from a bacterial pathogen can induce specific CTLs able to confer partial protection against bacterial challenge.
机译：以前我们已经表明，将疫苗衍生的细胞毒性T淋巴细胞（CTL）表位表达为短小基因的疫苗可以有效抵抗病毒攻击，在这里，我们将这些研究扩展到单核细胞增生李斯特菌。针对这种重要的人类病原体的宿主防御似乎主要由T细胞介导，并且已经在BALB / c小鼠中鉴定了来自李斯特菌溶血素O（LLO）蛋白的九聚体CTL表位。我们已经合成了该九聚体作为小基因，在重组牛痘病毒（VV-list）中表达了它，并用它来免疫小鼠。从经VV列表免疫的小鼠中培养的记忆CTL特异性裂解了用在LLO氨基酸残基91至99处鉴定出的九聚肽脉冲的靶细胞。免疫后四周，用单核细胞增生李斯特菌攻击小鼠。在亚致死剂量的单核细胞增生李斯特氏菌攻击后第6天，用VV-list免疫的小鼠在脾脏和肝脏中的细菌CFU减少了约2,000至6,000倍。此时，对于对照小鼠，细菌易于通过肝的革兰氏染色检测到，但在经VV列表免疫的动物中则无法检测到。另外，当给予正常致死剂量的细菌时，在VV列表免疫的动物中死亡延迟。这项研究表明，用仅携带来自细菌病原体的9个氨基酸的重组牛痘病毒进行的单次免疫可以诱导特定的CTL，这些CTL能够部分保护细菌免受攻击。

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