Yersinia pseudotuberculosis-based vaccines for plague and yersiniosis

基于假结核耶尔森氏菌的鼠疫和耶尔森氏菌疫苗

• 批准号: 9471106
• 负责人: Wei Sun
• 金额: $ 44.36万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9471106
• 关键词: Acute; Adjuvant; Animals; Antigens; Attention; Attenuated; Bacterial Vaccines; Biological Warfare; Blood Circulation; Cellular Immunity; Cessation of life; Dose; Economic Burden; Enteral; Fleas; Food Safety; Health; Heterophile Antigens; Hour; Human; Humoral Immunities; Immune response; Immunity; Immunization; Immunize; Infection; Innate Immune Response; Knowledge; Legal patent; Livestock; Modernization; Mus; Needles; Onset of illness; Oral; Oral Administration; Outcome; Pasteurella pseudotuberculosis; Persons; Plague; Plague Vaccine; Pneumonic Plague; Production; Public Health; Recombinants; Recording of previous events; Risk; Rodent; Safety; Salmonella Vaccines; Supplementation; Symptoms; System; Systemic infection; United States; Vaccine Production; Vaccines; Yersinia; Yersinia enterocolitica; Yersinia pestis; Zoonoses; adaptive immune response; attenuation; base; cost; experimental study; foodborne; immunogenicity; improved; mortality; pandemic disease; pathogen; prevent; protective efficacy; vaccine candidate; vaccine development; vector; vector vaccine; weapons

PROJECT SUMMARY Yersinia pestis, the causative agent of plague, has profoundly shaped human history by causing an estimated 200 million deaths amid three major pandemics. Considered to be a re-emerging pathogen, Y. pestis remains a public health issue and is responsible for several thousand worldwide annual cases of plague. Endemic plague foci persist through zoonotic circulation among rodent reservoir hosts and flea vectors. In addition to natural flea-borne acquisition, Y. pestis has an extensive history of biological warfare manipulations and is categorized as a prime threat for modern weaponization. Pneumonic plague, the most acute and threatening manifestation, is highly contagious and easily transmitted from person-to-person through airborne droplets, resulting in a rapid onset of disease and a mortality rate approaching 100% if treatment is delayed 24 hours beyond symptom onset. Currently, no licensed plague vaccines are available in the United States. Yersiniosis refers to an enteric infection by species of the genus Yersinia. There are two subtypes responsible for yersiniosis, Yersinia enterocolitica (Ye) and Yersinia pseudotuberculosis (Yptb). Ye and Yptb are fecal-oral zoonotic pathogens which ciruclate among environmental and a broad range of animal reserviors. Through incidental food-borne exposure, humans can develop yersiniosis, potentially culminating in systemic infection and postinfectious extraintestinal sequelae. In addition to direct human health risks, yersiniosis confers a considerable food-safety economic burden and is responsible for substantial livestock production loss. However, limited attention has been devoted toward vaccine development for yersiniosis. We have previously made substantial headway in the construction of a recombinant Yptb vector vaccine candidate aimed at preventing both plague and yersiniosis. Based upon our established recombinant attenuated Salmonella vaccine platform, a Yptb-based vaccine against plague and yersiniosis will impart several key advantages including (1) needle-free oral administration, (1) low-cost vaccine production, and (3) robust induction of humoral and cellular immune responses, and (4) human and environmental bait delivery. Additionally, we strive to elicit protective immunity upon a single dose without adjuvant supplementation. We previously demonstrated that immunization with attenuated Yptb strains elicits cross-protection against Y. pestis and Ye. Furthermore, immunogenicity against Y. pestis is readily enhanced by type 3 secretion system delivering heterologous antigens. Therefore, immunization with improved live attenuated Yptb strains shall stimulate cross-protective immunity against Y. pestis causing plague, and Ye and Yptb causing yersinosis.

项目摘要 鼠疫的致病因素耶尔西尼亚·佩斯蒂斯（Yersinia Pestis 在三个主要的大流行中，估计死亡2亿。被认为是一种重新出现的病原体Y. Pestis 仍然是一个公共卫生问题，并负责全球数千名瘟疫病例。 地方性鼠疫局灶性通过啮齿动物储层和跳蚤向量之间的人畜共患病持续存在。在 Y. Pestis是自然的跳蚤收购，拥有广泛的生物战术历史 并被归类为现代武器化的主要威胁。肺鼠疫，最急性和 威胁表现形式，具有高度传染性，很容易从人与人传播到空中 液滴，导致疾病迅速发作，如果治疗延迟，则接近100％的死亡率24 超出症状发作的小时。目前，美国没有持牌瘟疫疫苗。 耶尔森病是指耶尔森氏菌种类的肠道感染。有两个亚型 负责Yersiniisois，Yersinia肠结肠炎（YE）和耶尔森氏菌（Yersinia pseudotuberculculisois）（YPTB）。是的，YPTB 是粪便的人畜共患病原体，它们在环境和广泛的动物之间 预备役。通过偶然的食物传播，人类可以发展出耶尔森病，可能在 全身感染和感染后肠外后遗症。除了直接人类健康风险外， 耶尔森病赋予了相当大的食品安全经济负担，并负责实质性的牲畜 生产损失。然而，有限的关注已投入疫苗开发耶尔塞症。 我们以前在建造重组YPTB载体疫苗方面取得了长足的进展 旨在防止瘟疫和耶尔塞症的候选人。基于我们既定的重组 衰减的沙门氏菌疫苗平台，一种基于YPTB的疫苗针对鼠疫和耶尔森病 几个关键优势，包括（1）无针头给药，（1）低成本疫苗和（3） 强大的诱导体液和细胞免疫反应，以及（4）人类和环境诱饵的递送。 此外，我们努力在不补充辅助的单剂量时引起保护性免疫。我们 先前证明，通过减弱的YPTB菌株免疫引起对Y的交叉保护。 瘟疫和你们。此外，针对Y. Pestis的免疫原性很容易通过3型分泌系统增强 提供异源抗原。因此，通过改善活衰减的YPTB菌株的免疫接种应 刺激对Y. Pestis的交叉保护免疫，导致鼠疫，YE和YPTB引起耶拉索病。