Live attenuated Yersinia as vaccines against pneumonic plague

描述（由申请人提供）：鼠疫耶尔森菌是鼠疫的病原体，在人类历史上的几次流行中造成了高死亡率。据报道，全世界每年有数千例鼠疫病例，并且出现了对多种药物具有耐药性的鼠疫杆菌菌株。鼠疫已被世界卫生组织（who）列为再发疾病，鼠疫杆菌因其极强的毒性被认为是潜在的生物武器。尽管有这种需求，但目前在美国还没有获得许可的鼠疫疫苗。基于这些考虑，我们将构建高度减毒的鼠疫杆菌和假结核杆菌菌株，对其进行修饰，以表达高于正常水平的选定的鼠疫杆菌保护性抗原，作为疫苗使用。我们的研究将侧重于评估这些菌株对高剂量肺和皮下鼠疫杆菌的攻击的功效。携带鼠疫杆菌抗原（LcrV和/或F1）的假结核杆菌减毒疫苗菌株和选定的鼠疫杆菌疫苗菌株将被评估为口服疫苗，以应对肺炎和淋巴腺感染途径的高剂量鼠疫杆菌攻击。

DESCRIPTION (provided by applicant): Yersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. There are several thousand reported cases of the disease worldwide annually and an emergence of Y. pestis strains resistant to multiple drugs. Plague has been classified as a re-emerging disease by the World Health Organization and Y. pestis is considered a potential bioweapon owing to its extreme virulence. Despite a need, there are no licensed plague vaccines available in the United States currently. Because of these considerations, we will construct highly attenuated Y. pestis and Y. pseudotuberculosis strains modified to express selected Y. pestis protective antigens at higher than normal levels for use as vaccines. Our studies will focus on evaluating the efficacy of these strains against a high-dose pneumonic and subcutaneous Y. pestis challenge. Attenuated Y. pseudotuberculosis vaccine strains vectoring Y. pestis antigens (LcrV and/or F1) and selected Y. pestis vaccine strains will be evaluated as oral vaccines against high-dose Y. pestis challenges by both pneumonic and bubonic routes of infection. PUBLIC HEALTH RELEVANCE: Y. pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. There are no licensed plague vaccines available in the United States currently. We will explore using live attenuated Yersinia synthesizing high levels of selected Y. pestis antigens as a vaccine against bubonic and pneumonic plague. These studies will provide us with live attenuated Yersinia vaccine candidates suitable for use in humans and as a zoonotic vaccine suitable for use in rodent baits.