Evaluation and Production of a Multivalent Adenoviral Plague Vaccine

描述(由申请人提供)：这一第二阶段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，为人类临床试验做准备。之所以选择鼠疫疫苗项目，是因为人们越来越担心这种微生物可能会被用于恐怖主义活动。作为对这一威胁的回应，NIAID和CDC已将该生物体列为A类优先生物体。目前，还没有在生物恐怖主义事件中预防鼠疫的商业疫苗。这一担忧令人担忧，因为鼠疫杆菌的多重抗药性菌株在自然界中存在，或者已经被改造。该项目的第二阶段SBIR将专注于在腺病毒载体系统中生产和评估以低钙应答(LcrV)抗原和另外两种保护性鼠疫杆菌抗原CAF1(F1囊膜抗原)和YscF(3型分泌系统(T3SS)结构蛋白)为特征的候选疫苗。该项目将验证腺病毒疫苗鼻内接种可以在非人类灵长类动物(NHP)中诱导强大的保护性免疫反应的假设，以抵御全毒力鼠疫菌株CO92的气溶胶攻击。AIMS项目还将展示疫苗的大规模生产能力，这是应对储存或紧急情况所必需的。这一计划将通过威慑潜在恐怖分子在没有疫苗或治疗选择的情况下寻找武器，提供一条宝贵的第一道防线。此外，多价腺病毒疫苗的开发不仅对生物防御具有重要意义，而且对抗击全球传染病也具有重要意义。 公共卫生相关性：这一第二阶段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，为人类临床试验做准备。目前，没有获得许可的人用疫苗来预防感染鼠疫，尽管这种病原体在接触平民和军事人员时有能力造成广泛的发病率和死亡率。

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.