首页> 美国卫生研究院文献>Vaccines >Deletion of Two Genes in Burkholderia pseudomallei MSHR668 That Target Essential Amino Acids Protect Acutely Infected BALB/c Mice and Promote Long Term Survival
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Deletion of Two Genes in Burkholderia pseudomallei MSHR668 That Target Essential Amino Acids Protect Acutely Infected BALB/c Mice and Promote Long Term Survival

机译:靶向必需氨基酸的假伯克霍尔德氏菌MSHR668中的两个基因的缺失可保护急性感染的BALB / c小鼠并促进长期存活

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摘要

Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen . It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine against melioidosis. In this study, multiple MSHR668 deletion mutants were evaluated as live attenuated vaccines in the sensitive BALB/c mouse model of melioidosis. The most efficacious vaccines after an intraperitoneal challenge with 50-fold over the 50% median lethal dose (MLD ) with K96243 were 668 Δ and 668 Δ . Both vaccines completely protected mice in the acute phase of infection and showed significant protection (50% survivors) during the chronic phase of infection. The spleens of the survivors that were examined were sterile. Splenocytes from mice vaccinated with 668 Δ and 668 Δ expressed higher amounts of IFN-γ after stimulation with antigens than splenocytes from mice vaccinated with less protective candidates. Finally, we demonstrate that 668 Δ is nonlethal in immunocompromised NOD/SCID mice. Our results show that 668 Δ and 668 Δ provide protective cell-mediated immune responses in the acute phase of infection and promote long term survival in the sensitive BALB/c mouse model of melioidosis.
机译:拟鼻病是一种由兼性细胞内病原体引起的疾病。它本质上对许多抗生素具有抗性,宿主风险因素在感染易感性中起主要作用。当前,没有针对类鼻疽的人或动物疫苗。在这项研究中,多个MSHR668缺失突变体被评估为类li病的敏感BALB / c小鼠模型中的减毒活疫苗。腹膜内攻击后,K96243的50%中值致死剂量(MLD)的50倍以上,最有效的疫苗为668Δ和668Δ。两种疫苗均在感染的急性期完全保护了小鼠,并在感染的慢性期表现出了显着的保护作用(50%存活者)。检查的幸存者的脾脏是无菌的。抗原刺激后,接种了668Δ和668Δ的小鼠的脾细胞表达的IFN-γ量高于接种了较少保护性候选物的小鼠的脾细胞。最后,我们证明了668Δ在免疫受损的NOD / SCID小鼠中非致死性。我们的结果表明,在急性感染期668Δ和668Δ可提供保护性的细胞介导的免疫反应,并能在敏感的类腮腺BALB / c小鼠模型中促进长期存活。

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