Chlamydia pneumoniae vaccine candidates

描述(申请人提供)：衣原体(C.)肺炎是一种主要病原体 社区获得性上呼吸道和下呼吸道感染和肺炎。 越来越多的证据表明肺炎衣原体感染在 在发达国家动脉粥样硬化性冠心病中的作用 肺炎衣原体是一个主要的公共卫生问题。这显然值得努力 研制肺炎衣原体疫苗，用于预防或治疗肺炎 呼吸系统疾病，可能还有冠心病和动脉粥样硬化。 使用我们的新基因免疫技术，我们能够解开 病原体的基因组成为最好的候选疫苗，最近已经 在鹦鹉螺杆菌感染的小鼠模型中验证了这一点，在该模型中，我们发现了10 保护性基因也保护原始宿主动物。细读 肺炎衣原体的完整基因组序列，我们建议作为迈向 肺炎衣原体疫苗I)检测肺炎衣原体的同源物 鹦鹉热链球菌保护性基因在小鼠模型中的保护效果 肺炎肺炎呼吸道感染；ii)进行肺炎衣原体全基因组检查 寻找最佳抗原介导鸡传染性支气管炎预防性免疫 呼吸道感染；以及iii)进行实验以了解 这种免疫干预成功的机制。我们建议 具体目标如下：1)检测10株肺炎衣原体同源物 保护性鹦鹉热杆菌基因在小鼠预防性呼吸模型中的应用。 肺炎感染。2)筛选所有约1,000个肺炎衣原体基因 它们在小鼠预防模型中的保护作用。3)了解 在异种繁殖的人类群体中可能的反应光谱，解剖 肺炎衣原体介导疾病保护作用的免疫学机制 几种近交系在呼吸系统疾病模型中的疫苗候选蛋白 老鼠品系。

DESCRIPTION (Provided by Applicant): Chlamydia (C.) pneumoniae is a major agent of community-acquired upper and lower respiratory infection and pneumonia. Increasing evidence suggests that C. pneumoniae infection plays an integral role in atherosclerotic coronary heart disease in developed countries, making C. pneumoniae a major public health concern. This clearly merits an effort to develop a vaccine against C. pneumoniae for prevention or treatment of respiratory disease, and possibly coronary heart disease and atherosclerosis. Using our new genetic immunization technologies, we are able to deconvolute the genomes of pathogens into the best vaccine candidates, and have recently validated this in a mouse model of C. psittaci infection in which we found 10 protective genes that also protect the original host animal. Perusing the complete genome sequence of C. pneumoniae, we propose as first step towards a C. pneumoniae vaccine to i) examine the C. pneumoniae homologs of the protective C. psittaci genes for protective efficacy in a mouse model of C. pneumoniae respiratory infection; ii) conduct a C. pneumoniae genome-wide search for the best antigens mediating prophylactic immunity against respiratory infection; and iii) perform experiments to understand the mechanisms for the success of such immunological intervention. We propose the following specific aims: 1) Test the C. pneumoniae homologs of the 10 protective C. psittaci genes in a mouse prophylactic respiratory model of C. pneumoniae infection. 2) Screen all approximately 1,000 C. pneumoniae genes for their protective efficacy in the mouse prophylactic model. 3) To understand the spectrum of possible responses in an outbred human population, dissect the immunological mechanisms of disease protection mediated by the C. pneumoniae vaccine candidate proteins in respiratory disease models using several inbred mouse strains.