Yersinia Outer-Membrane-Vesicle Vaccines Against Pneumonic Plague

摘要 鼠疫耶尔森氏菌是鼠疫的病原体，在几次流行中造成了高死亡率。 纵观人类历史。世界卫生组织将鼠疫列为一种新出现的疾病 由于全世界每年有数千例这种疾病的报告病例， 近年来出现了多药耐药的鼠疫耶尔森菌菌株。鼠疫杆菌已被用作一种生物 人类历史上记载的武器，是恐怖分子最有可能使用的生物威胁之一。 目前，西方世界还没有获得许可的鼠疫疫苗。毒力F1阴性Y.的分离 来自自然来源的鼠疫菌株和耶尔森氏菌中lcrV基因多态性的存在可能导致鼠疫杆菌 逃避LcrV和F1抗原诱导的保护性免疫的变异体。因此，疫苗仅基于 对LcrV和F1的抗原不足以保证对人类鼠疫的长期防御。为了 克服了由LcrV和F1抗原组成的亚单位疫苗的缺点，我们建议使用Y. 伪结核OMV作为鼠疫无细胞疫苗：(1)构建Yptb株 强健地生产携带一系列鼠疫保护性抗原的高度免疫原性自我调节的OMV； (2)评价OMVS对啮齿动物(小鼠和大鼠)的保护性免疫。(三)认真破译公司治理机制 耶尔森氏菌OMV诱导的免疫保护作用为研制合理的鼠疫疫苗奠定基础 发展。最后，该项目的成功将为以下人群提供高效安全的鼠疫疫苗 人类。

SUMMARY Yersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. Plague has been classified as a re-emerging disease by the World Health Organization since there are several thousand reported cases of the disease worldwide annually and multidrug-resistant Y. pestis strains occur in recent years. The plague bacillus has been used as a biological weapon recorded in human history and is one of the more likely biological threats to be used by terrorists. Currently, no licensed plague vaccines are available in Western world. Isolation of virulent F1-negative Y. pestis strains from natural sources and the existence of lcrV polymorphisms in Yersinia may result in Y. pestis variants that escape protective immunity induced by LcrV and F1 antigens. Therefore, vaccines solely based upon LcrV and F1 antigens is insufficient to guarantee long-term defense against plague in humans. In order to overcome the drawbacks of subunit vaccines composed of LcrV and F1 antigens, we propose to use Y. pseudotuberculosis (Yptb) OMVs as an acellular vaccine against plague: (1) Construct Yptb strains which robustly produce highly immunogenic self-adjuvanting OMVs carrying an array of Y. pestis protective antigens; (2) Evaluate protective immunity of OMVs in rodents (mouse and rat). (3) Carefully decipher mechanisms of immune protection induced by the Yersinia OMVs to provide fundamentals for rational plague vaccine development. Finally, the success of this project will provide highly effective and safe plague vaccines for humans.