Immunity Induced by Modified Adenovirus Fiber

描述(申请人提供)：这项建议旨在阐明腺病毒衣壳纤维蛋白在刺激免疫系统和为基因疫苗运送抗原方面的作用。在Ad衣壳中掺入抗原是一种利用Ad免疫原性的新策略，也是一种绕过先前存在的抗Ad免疫的方法。初步研究表明，将表位整合到Ad衣壳中最有希望的部位是纤维蛋白。总的假设是，将表位结合在Ad纤维蛋白的最佳位置可以激发强大的保护性抗表位免疫，即使在存在抗Ad免疫的情况下。纤维修饰对抗原提呈和抗Ad免疫的影响知之甚少。纤维修饰对抗原提呈和抗Ad免疫的影响知之甚少。从这些研究中获得的知识不仅将有助于发展基于Ad的疫苗，而且将有助于确定Ad纤维在Ad免疫原性中的作用机制。两个特定的目标将检验整个假设：目标1将评估模型表位在Ad纤维蛋白中的位置将影响与靶细胞的相互作用、抗原呈递和抗表位免疫反应的假设。目的2将评估一种假设，即来自两种细菌病原体的膜结合和分泌抗原的表位被结合到Ad纤维蛋白的最佳位置，在存在预先存在的抗Ad免疫的情况下可以诱导保护性免疫。来自铜绿假单胞菌外膜蛋白F和炭疽杆菌保护性抗原的表位将被插入到Ad纤维的最佳位置，并评估其诱导细胞、体液和保护性抗表位免疫反应的潜力。新的疫苗方法，如这里提出的，将与公共卫生相关。它们可以帮助开发针对没有或没有好的疫苗可用的感染的疫苗。在上个世纪，成功的疫苗对传染病的预防产生了深远的影响。

DESCRIPTION (provided by applicant): This proposal aims to elucidate the role of adenovirus (Ad) capsid fiber protein to stimulate the immune system and to deliver antigens for genetic vaccination. Incorporation of antigens into the Ad capsid is a novel and promising strategy to capitalize on the immunogenic properties of Ad and a way to circumvent preexisting anti-Ad immunity. Preliminary studies show that the most promising site for the integration of an epitope into the Ad capsid is the fiber protein. The overall hypothesis is that incorporation of epitopes in the optimal location of the Ad fiber protein can evoke potent protective anti-epitope immunity even in the presence of anti-Ad immunity. Little is known about the effect of fiber modifications on antigen presentation and anti-Ad immunity. Little is known about the effect of fiber modifications on antigen presentation and anti-Ad immunity. The knowledge gained from the proposed studies will not only be useful in the development of Ad-based vaccines, but also to identify mechanisms of the role the Ad fiber in the immunogenicity of Ad. Two specific aims will test the overall hypothesis: Aim 1 will evaluate the hypothesis that the location of a model epitope within the Ad fiber protein will influence interaction with target cells, antigen presentation and anti-epitope immune responses. Aim 2 will evaluate the hypothesis that epitopes derived from a membrane-bound and secreted antigen of two bacterial pathogens incorporated into an optimal location of the Ad fiber protein can induce protective immunity in the presence of pre-existing anti-Ad immunity. Epitopes from the Pseudomonas aeruginosa outer membrane protein F and the Bacillus anthracis protective antigen will be inserted in the optimal position of the Ad fiber, and evaluated in their potential to elicit cellular, humoral and protective anti-epitope immune responses. New methods for vaccines, as the one proposed here, will be relevant for the public health. They can aid in the development of vaccines for infections against which no or no good vaccines are available. Successful vaccines have had a profound impact on the prevention of infectious diseases over the last century.