Immunity Induced by Modified Adenovirus Fiber

描述（由申请方提供）：本提案旨在阐明腺病毒（Ad）衣壳纤维蛋白在刺激免疫系统和递送抗原用于基因疫苗接种中的作用。将抗原并入到Ad衣壳中是利用Ad的免疫原性的新颖且有前景的策略，并且是规避预先存在的抗Ad免疫的方式。初步研究表明，将表位整合到Ad衣壳中最有希望的位点是纤维蛋白。总的假设是，在Ad纤维蛋白的最佳位置掺入表位可以引起有效的保护性抗表位免疫，即使在抗Ad免疫的存在下。纤维修饰对抗原呈递和抗Ad免疫的影响知之甚少。纤维修饰对抗原呈递和抗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开发基于Ad的疫苗，而且还将有助于确定Ad纤维在Ad免疫原性中的作用机制。两个具体目标将测试总体假设：目标1将评估Ad纤维蛋白内模型表位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应答的假设。目的2将评估的假设，来自两种细菌病原体的膜结合和分泌的抗原的表位纳入Ad纤维蛋白的最佳位置，可以诱导保护性免疫的存在下，预先存在的抗Ad免疫。将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插入Ad纤维的最佳位置，并评估其引发细胞、体液和保护性抗表位免疫应答的潜力。这里提出的疫苗新方法将与公共卫生有关。它们可以帮助开发针对没有或没有良好疫苗的感染的疫苗。成功的疫苗对上个世纪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.