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.

概括 鼠疫的病因学因素耶尔西尼亚·佩斯蒂斯（Yersinia Pestis）已导致几种流行病的高死亡率 在整个人类历史上。瘟疫已被世界卫生归类为一种重新出现的疾病 组织每年有数千例报告该病的病例，并且 近年来发生了抗多药Y.鼠疫菌株。瘟疫已被用作生物学 武器记录在人类历史上，是恐怖分子使用的最可能使用的生物学威胁之一。 目前，西方世界没有持牌瘟疫疫苗。分离有毒的F1阴性Y。 耶尔森氏菌中的天然来源和LCRV多态性的存在可能导致鼠疫 LCRV和F1抗原引起的保护性免疫的变体。因此，疫苗仅基于 在LCRV和F1时，抗原不足以保证对人类瘟疫的长期防御。为了 克服由LCRV和F1抗原组成的亚基疫苗的缺点，我们建议使用Y。 假结核（YPTB）OMV作为针对鼠疫的细胞疫苗：（1）构造YPTB菌株 稳健地产生高度免疫原性的自我辅助OMV，携带一系列鼠疫霉菌保护性抗原； （2）评估OMV在啮齿动物（小鼠和大鼠）中的保护性免疫。 （3）仔细的破译机制 Yersinia OMV引起的免疫保护提供了理性瘟疫疫苗的基础知识 发展。最后，该项目的成功将为 人类。