Yersinia Outer-Membrane-Vesicle Vaccines Against Pneumonic Plague

鼠疫耶尔森氏菌外膜囊泡疫苗

• 批准号: 10673295
• 负责人: Wei Sun
• 金额: $ 25.41万
• 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/10673295
• 关键词: Acellular Vaccines; Adjuvant; African Green Monkey; Animals; Antibody Response; Antigen-Presenting Cells; Antigens; Attenuated Vaccines; B-Lymphocytes; Bacillus; Bacteria; Biological; Biological Warfare; Case Study; Centers for Disease Control and Prevention (U.S.); Characteristics; County; Cytosol; DNA; Disease; Dose; 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; Lipids; Lipopolysaccharides; Lung; Macaca fascicularis; Mass Vaccinations; Mediating; Membrane; Modification; Multi-Drug Resistance; Mus; National Security; 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; base; 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 鼠疫耶尔森氏菌是鼠疫的病原体，在多种流行病中造成高死亡率 贯穿人类历史。鼠疫已被世界卫生组织列为重新出现的疾病 组织，因为全世界每年有数千起该疾病的报告病例， 近年来出现了多重耐药鼠疫杆菌菌株。鼠疫杆菌已被用作生物制剂 人类历史上有记录的武器，是恐怖分子最有可能使用的生物威胁之一。 目前，西方世界还没有获得许可的鼠疫疫苗。分离有毒力的 F1 阴性 Y。 天然来源的鼠疫菌株以及耶尔森氏菌中 lcrV 多态性的存在可能导致鼠疫耶尔森氏菌 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 LcrV 和 F1 抗原不足以保证人类对鼠疫的长期防御。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。 假结核病 (Yptb) OMV 作为抗鼠疫的无细胞疫苗：(1) 构建 Yptb 菌株，其 稳健地产生携带一系列鼠疫耶尔森氏菌保护性抗原的高免疫原性自我辅助 OMV； (2)评价啮齿动物(小鼠和大鼠)中OMV的保护性免疫。 （三）认真解读机制 耶尔森氏菌OMV诱导的免疫保护为合理鼠疫疫苗提供基础 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。