Yersinia Outer-Membrane-Vesicle Vaccines Against Pneumonic Plague

鼠疫耶尔森氏菌外膜囊泡疫苗

• 批准号: 10555332
• 负责人: Wei Sun
• 金额: $ 70.69万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-25 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555332
• 关键词: Accidents; Acellular Vaccines; Adjuvant; African Green Monkey; Animals; Antibody Response; Antigen-Presenting Cells; Antigens; Attenuated Vaccines; B-Lymphocytes; Bacillus; Bacteria; Biological; Biological Warfare; Case Study; Characteristics; Classification; County; Cytosol; DNA; Disease; Dose; Drug Metabolic Detoxication; Economic Development; Epidemic; Etiology; FDA approved; Genetic; Genetic Polymorphism; Genetic Variation; Glycerophospholipids; Gram-Negative Bacteria; Grant; Human; Immune; Immune response; Immunity; Immunization; Infection; Inflammatory Response; Inhalation; Left; Licensing; Lipids; Lipopolysaccharides; Lung; Macaca fascicularis; Mass Vaccinations; Mediating; Membrane; Modification; Multi-Drug Resistance; Mus; National Security; Natural Source; Neisseria; Orphan Drugs; Pasteurella pseudotuberculosis; Phase III Clinical Trials; Plague; Plague Vaccine; Pneumonic Plague; Proteins; RNA; Rattus; Recording of previous events; Rodent; Role; Route; Safety; Shapes; Source; Subunit Vaccines; Symptoms; T cell response; T-Lymphocyte; Vaccination; Vaccines; Variant; Vesicle; Virulent; Western World; World Health Organization; Yersinia; Yersinia pestis; Zoonoses; adaptive immune response; aerosolized; bioweapon; immunogenic; immunogenicity; improved; mortality; nanosized; nanovesicle; pathogen; periplasm; prevent; protective efficacy; respiratory; response; success; transmission process; vaccine access; vaccine candidate; vaccine development; vesicular release; weapons

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.

总结 鼠疫耶尔森氏菌是鼠疫的病原体，在几次流行病中造成高死亡率 在人类历史上。鼠疫已被世界卫生组织列为重新出现的疾病 由于全世界每年有数千例报告的病例， 多药耐药Y.近年来出现鼠疫菌株。鼠疫杆菌已经被用作生物制剂， 这是人类历史上最有记录的生物武器，也是恐怖分子最有可能使用的生物威胁之一。 目前，在西方世界没有获得许可的鼠疫疫苗。分离到强毒F1阴性Y. 自然来源的鼠疫菌和耶尔森氏菌中lcrV多态性的存在可能导致耶尔森氏菌的致病性。鼠疫 逃避LcrV和F1抗原诱导的保护性免疫的变体。因此，疫苗仅基于 对LcrV和F1抗原的免疫不足以保证对人类鼠疫的长期防御。为了 为了克服LcrV和F1抗原组成的亚单位疫苗的缺点，我们建议使用Y. 假结核（Yptb）OMV作为鼠疫无细胞疫苗的研究：（1）构建Yptb菌株， 稳健地产生携带Y的阵列的高免疫原性自佐剂OMV。鼠疫保护性抗原; (2)评价啮齿类动物（小鼠和大鼠）中OMV的保护性免疫。(3)仔细解读 耶尔森氏菌OMV诱导的免疫保护作用为鼠疫疫苗的合理研制提供基础 发展最后，该项目的成功将为人类提供高效、安全的鼠疫疫苗， 人类