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.

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