Live attenuated Yersinia as vaccines against pneumonic plague

描述（由申请人提供）：鼠疫耶尔森氏菌是鼠疫的病原体，在人类历史上的几次流行病中导致高死亡率。全世界每年有数千例该病的报道，Y。对多种药物有抗药性的鼠疫菌株。鼠疫已被世界卫生组织和Y.鼠疫因其极强的毒性而被认为是一种潜在的生物武器。尽管有需求，但目前美国没有获得许可的鼠疫疫苗。由于这些考虑，我们将构建高度减毒的Y。鼠疫菌和Y.假结核菌株被修饰以表达选择的Y.鼠疫保护性抗原高于正常水平，用作疫苗。我们的研究将集中于评估这些菌株对高剂量肺炎和皮下接种的Y。鼠疫挑战减毒的假结核病疫苗株介导Y.鼠疫抗原（LcrV和/或F1）和选择的Y.鼠疫疫苗株将作为针对高剂量Y.鼠疫通过肺炎和腺鼠疫两种途径感染。

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.