Evaluation and Production of a Multivalent Adenoviral Plague Vaccine

描述（由申请人提供）：该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回应人们对这种生物可能被用于恐怖主义事件的日益关注。为了应对这一威胁，NIAID和CDC已将该生物列为a类优先生物。目前，市面上还没有在发生生物恐怖主义事件时预防鼠疫的疫苗。这一担忧令人担忧，因为鼠疫杆菌鼠疫杆菌具有多重抗生素耐药性的菌株存在于自然界或已被改造。该II期SBIR将专注于生产和评估一种候选疫苗，该疫苗具有低钙反应（LcrV）抗原与另外两种具有保护性的鼠疫菌抗原，即Caf1 （F1荚膜抗原）和YscF（3型分泌系统（T3SS）结构蛋白），在腺病毒载体系统中联合使用。该项目将测试一种假设，即单次鼻内给药腺病毒疫苗可以在非人灵长类动物（NHPs）中引起强烈的保护性免疫反应，以抵御具有完全毒力的鼠疫杆菌菌株CO92的气溶胶攻击。项目目标还将展示疫苗的大规模生产能力，以满足储存或紧急情况的需要。这一项目将为寻找武器的潜在恐怖分子提供宝贵的第一道防线，防止他们在没有疫苗或治疗方案的情况下获得武器。此外，多价腺病毒疫苗的开发不仅对生物防御，而且对对抗全球性传染病具有重要意义。

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.