Increasing efficacy of an Adenovirus vaccine targeting Clostridium difficile usin

描述（由申请人提供）：艰难梭菌是发展中国家最具问题的细菌病原体之一，在美国每年有超过30万例病例。C.预计在未来两年内，艰难梭菌感染率将上升40%，相关医疗费用将达到数十亿美元。由于抗生素治疗常促进C.因此，需要更有效的策略来治疗这些感染。在这里，我们建议开发一个创新的下一代腺病毒（Ad）为基础的疫苗靶向C。两个PI实验室开发的技术难以结合。基于非复制型Ad的疫苗提供了独特的、强大的疫苗递送平台，因为编码所需抗原的基因直接从重组Ad载体表达。我们的初步结果开发了表达C.艰难梭菌TA毒素已显示出作为疫苗候选者的前景。然而，作为一种治疗剂来快速减轻感染C.艰难梭菌，需要产生快速的体液应答。可以实现这一点的一种机制是将免疫刺激性佐剂分子包含在疫苗中。在这里，我们提出了一种新的方法来提高之前构建的C的功效。艰难梭菌Ad疫苗通过包含佐剂（为了保护知识产权，排除了具体细节）。这些实验可能会导致一种新的C疫苗的开发。很难此外，我们的结果将是概念验证，这种佐剂的掺入可以增加基于病毒和DNA的疫苗预防传染病和其他疾病，如癌症的功效。

DESCRIPTION (provided by applicant): Clostridium difficile is one of the most problematic bacterial pathogens in developing countries with over 300,000 cases in the US annually. Cases of C. difficile are predicted to rise 40% over the next two years with billions of dollars of associated medical expenses. As antibiotic therapy often promotes colonization of C. difficile, more effective strategies to treat these infections are needed. Here, we propose to develop an innovative next generation Adenovirus (Ad) based vaccine targeting C. difficile combining technologies developed in the two PI's laboratories. Nonreplicating Ad based vaccines offer a unique, powerful vaccine delivery platform as genes encoding a desired antigen are directly expressed from the recombinant Ad vector. Our preliminary results developed a base Ad vaccine expressing a non-toxic portion of the C. difficile TA toxin that has shown promise as a vaccine candidate. However, to function as a therapeutic to rapidly reduce symptoms of individuals infected with C. difficile, generation of a rapid humoral response is required. One mechanism by which this can be achieved is the inclusion of an immunostimulatory adjuvant molecule into the vaccine. Here, we propose a novel approach to increase the efficacy of the previously constructed C. difficile Ad vaccine by inclusion of an adjuvant (specific details are excluded for protection of intellectual property). These experiments may lead to the development of a new vaccine for C. difficile. Additionally, our results will be proof-of-concept incorporation of this adjuvant can increase the efficacy of viral and DNA based vaccines to prevent infectious disease and other diseases, such as cancer.