Increasing efficacy of an Adenovirus vaccine targeting Clostridium difficile usin

描述(申请人提供)：艰难梭菌是发展中国家最有问题的细菌病原体之一，每年在美国有超过30万例病例。艰难梭菌的病例预计将在未来两年增加40%，相关的医疗费用将达到数十亿美元。由于抗生素治疗经常促进艰难梭菌的定植，因此需要更有效的策略来治疗这些感染。在这里，我们建议开发一种创新的针对艰难梭菌的下代腺病毒(Ad)疫苗，结合PI的两个实验室开发的技术。非复制型Ad疫苗提供了一个独特的、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载体中表达出来。我们的初步结果开发了一种基础Ad疫苗，它表达艰难梭菌TA毒素的无毒部分，已显示出作为疫苗候选的前景。然而，要发挥治疗作用，迅速减轻艰难梭菌感染者的症状，就需要产生快速的体液反应。实现这一目标的一种机制是在疫苗中加入免疫刺激佐剂分子。在这里，我们提出了一种新的方法，通过加入佐剂来提高先前构建的艰难梭菌Ad疫苗的效力(出于知识产权保护的考虑，具体细节被排除在外)。这些实验可能会导致艰难梭菌新疫苗的开发。此外，我们的结果将是概念验证，加入这种佐剂可以提高病毒和DNA疫苗预防传染病和其他疾病(如癌症)的效力。

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.