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首页> 外文期刊>Clinical and vaccine immunology: CVI >Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague
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Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

机译：用鼠疫耶尔森氏菌CO92的活检三联突变体对小鼠进行肌内免疫诱导鲁棒的体液和细胞介导的免疫，从而完全保护动物免受肺炎鼠疫的侵害

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Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 106 CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD50) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but with a much diminished virulence potential.
机译：先前，我们显示了鼠疫耶尔森菌CO92的Δ lpp Δ msbB Δ ail 三重突变体，其中缺失了编码Braun脂蛋白（Lpp）的基因肺鼠疫的小鼠模型中，酰基转移酶（MsbB）和附着侵袭位点（Ail）均无毒。在这项研究中，我们通过不同的疫苗接种途径进一步评估了Δ lpp Δ msbB Δ ail 三重突变体及其衍生物的免疫原性。通过皮下（s.c.）或肌内（i.m.）途径以两次剂量（2×10 6 CFU /剂量）的上述三重突变体对小鼠进行免疫，动物的存活率为100％。随后接受70至92 50％致死剂量（LD 50 ）野生型（WT）菌株CO92的肺炎攻击，当免疫接种后，所有小鼠均存活。路线。由于Ail具有毒力和免疫原性，因此创建了一个不具有毒力特性的Ail突变体，并且基因修饰的 ail 替换了其染色体上的天然 ail 基因Δ lpp Δ msbB 双突变体，创建一个Δ lpp Δ msbB :: ailL2 疫苗株。当由i.m给药时，这种新产生的突变体与Δ lpp Δ msbB Δ ail 三重突变体相似地减毒。并为动物提供了100％的保护，使其免受随后的肺炎攻击。不仅上述两个突变体从最初的i.m迅速清除。在没有组织病理学损伤的动物中注射部位，被免疫的小鼠在免疫期间或随后暴露于WT CO92后没有表现出任何疾病症状。这两个突变体触发了基于Th1和Th2的平衡抗体反应以及细胞介导的免疫。接种小鼠的T细胞（Th17细胞的细胞因子）中白细胞介素17（IL-17）的大量增加，进一步增强了它们的疫苗潜力。因此，Δ lpp Δ msbB Δ ail 和Δ lpp Δ msbB ： ： ailL2 突变体是鼠疫的极好的候选疫苗，后一种突变体仍保留Ail的免疫原性，但毒力潜力大大降低。

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