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: 8253000
• 负责人: ASHOK K CHOPRA
• 金额: $ 99.55万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253000
• 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. PUBLIC HEALTH RELEVANCE: 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. Currently there is no licensed vaccine for human use to protect against infection with plague despite the pathogen's capability to inflict widespread morbidity and mortality upon exposure to both civilians and military personnel.

描述（由申请人提供）：本II期SBIR的最终目标是完成鼠疫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应对人们对这种生物体可能用于恐怖主义事件的日益关注。NIAID和CDC针对这一威胁，已将该生物体列为A类优先生物体。目前，还没有商业上可获得的疫苗在发生生物恐怖主义事件时预防鼠疫。这种担忧是令人担忧的，因为鼠疫杆菌的多重抗生素耐药菌株，Y。鼠疫，存在于自然界或已被工程。该II期SBIR的项目目标将集中于生产和评价一种候选疫苗，其特征是低钙应答（LcrV）抗原与其他两种保护性Y。鼠疫抗原，即Caf1（F1荚膜抗原）和YscF（3型分泌系统（T3SS）结构蛋白）。该项目将检验以下假设：腺病毒疫苗的单次鼻内给药可在非人灵长类动物（NHP）中引发强保护性免疫应答，以对抗完全毒性Y的气溶胶攻击。鼠疫CO92菌株。项目目标还将展示疫苗的大规模生产能力，以满足库存或紧急情况的需要。该计划将提供一个宝贵的第一道防线，威慑潜在的恐怖分子，在没有疫苗或治疗方案的情况下寻找武器。此外，多价腺病毒疫苗的开发不仅对于生物防御而且对于对抗全球性传染病具有重要意义。 公共卫生关系：该II期SBIR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。目前，尽管鼠疫病原体能够在平民和军事人员接触后造成广泛的发病率和死亡率，但没有许可的疫苗可供人类使用，以防止感染鼠疫。