Evaluation and Production of a Multivalent Adenoviral Plague Vaccine

多价腺病毒鼠疫疫苗的评价和生产

• 批准号: 8690739
• 负责人: ASHOK K CHOPRA
• 金额: $ 95.1万
• 依托单位: NORWELL, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-18 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690739
• 关键词: Academia; Adenovirus Vector; Adenoviruses; Aerosols; Antibiotic Resistance; Antigens; Bacteria; Bioterrorism; Bubonic Plague; Bypass; Calcium; Categories; Centers for Disease Control and Prevention (U.S.); Clinical Research; Clinical Trials; Communicable Diseases; Computers; Data; Development; Emergency Situation; Engineering; Ensure; Evaluation; Event; Exposure to; Gene Transfer; Grant; Housing; Human; Immune response; Immunity; Immunization; Industry; Infection; Intellectual Property; Intranasal Administration; Investigational Drugs; Laboratories; Legal patent; Licensing; Macaca; Methods; Military Personnel; Modeling; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Nature; Nose; Organism; Phase; Phase I/II Trial; Plague; Plague Vaccine; Pneumonic Plague; Preparation; Production; Progress Reports; Research; Research Personnel; Route; Safety; Small Business Innovation Research Grant; Structural Protein; System; Technology; Terrorism; Testing; Vaccination; Vaccines; Veterinarians; Virulent; Yersinia pestis; aerosolized; base; biodefense; capsule; combat; emergency service responder; large scale production; meetings; mortality; mouse model; neutralizing antibody; nonhuman primate; pathogen; phase 1 study; preclinical study; programs; quality assurance; resistant strain; response; scale up; success; vaccine candidate; vector; weapons

DESCRIPTION (provided by applicant): The final objective of this Phase II SBIR is to complete preclinical studies of a trivalent adenoviral vaccine against plague in preparation for human clinical trials. The plague vaccine project was selected in response to the growing concern surrounding the organism's possible use in a terrorism event. The NIAID and CDC, in response to this threat, has classified the organism as a Category A priority organism. Currently, there are no commercially available vaccines for protection against plague in the instance of a bioterrorism event. This concern is alarming, as multi-antibiotic-resistant strains of the plague bacterium, Y. pestis, exist in nature or have been engineered. Project Aims for this Phase II SBIR will focus on the production and evaluation of a vaccine candidate featuring the low calcium response (LcrV) antigen in combination with two other protective Y. pestis antigens, namely Caf1 (F1 capsular antigen) and YscF (a type 3 secretion system (T3SS) structural protein), in an adenoviral vector system. The project will test the hypothesis that a single, intranasal administration of the adenoviral vaccine can elicit a strong protective immune response in non-human primates (NHPs) against aerosol challenge with the fully virulent Y. pestis strain CO92. Project aims will also demonstrate the large-scale production capability of the vaccine necessary for meeting stockpiling or emergency scenarios. This program will provide a valuable first line of defense by deterrence for potential terrorists in search of weapons where no vaccine or treatment option exists. Further, the development of a multivalent adenoviral vaccine is not only significant for biodefense but also for combating global infectious disease.

描述（由申请人提供）：本次SBIR II期的最终目标是完成针对鼠疫的三价腺病毒疫苗的临床前研究，为人体临床试验做准备。选择鼠疫疫苗项目是为了回应人们对鼠疫可能被用于恐怖主义事件的日益担忧。为了应对这一威胁，NIAID 和 CDC 已将该生物体列为 A 类优先生物体。目前，还没有商用疫苗可以在生物恐怖主义事件中预防鼠疫。这种担忧令人担忧，因为鼠疫细菌鼠疫耶尔森菌的多重抗生素耐药菌株存在于自然界中或已经被工程改造过。该 II 期 SBIR 的项目目标将重点是生产和评估一种候选疫苗，该疫苗具有低钙反应 (LcrV) 抗原与其他两种保护性鼠疫耶尔森抗原的组合，即 Caf1（F1 荚膜抗原）和 YscF（一种类型）。 3 分泌系统（T3SS）结构蛋白），位于腺病毒载体系统中。该项目将测试这样的假设：单次鼻内施用腺病毒疫苗可以在非人灵长类动物 (NHP) 中引发强烈的保护性免疫反应，以抵抗完全毒力的鼠疫耶尔森菌株 CO92 的气溶胶攻击。项目目标还将展示满足库存或紧急情况所需的疫苗的大规模生产能力。该计划将为在没有疫苗或治疗方案的情况下寻找武器的潜在恐怖分子提供威慑作用，提供宝贵的第一道防线。此外，多价腺病毒疫苗的开发不仅对于生物防御具有重要意义，而且对于对抗全球传染病也具有重要意义。