Immunity Induced by Modified Adenovirus Fiber

修饰腺病毒纤维诱导免疫

基本信息

批准号：
8079111
负责人：
Stefan Worgall
金额：
$ 40.38万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-15 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8079111
关键词：
Address Adenovirus Vector Adenovirus hexon capsid protein Adenoviruses Adjuvant Antibodies Antibody Formation Antigen Presentation Antigen-Presenting Cells Antigens Avidity B-Lymphocytes Bacterial Toxins Binding Capsid Capsid Proteins Cells Cellular Immunity Code Communicable Diseases Data Dendritic Cells Development Epitopes Fiber Genes Goals Haplotypes Hemagglutinin Immune response Immune system Immunity Immunization In Vitro Infection Influenza Hemagglutinin Knowledge Ligands Location Membrane Membrane Proteins Methods Modeling Modification Mouse Strains Mus OprF protein Peptides Play Positioning Attribute Prevention Property Proteins Pseudomonas aeruginosa Public Health Respiratory System Respiratory tract structure Role Site T-Lymphocyte Testing Tropism Vaccines adenovirus penton protein adenovirus receptor anthrax protective factor base clinically relevant genetic vaccine immunogenic immunogenicity in vivo neutralizing antibody novel novel strategies pathogen response soluble fiber tool trafficking vaccine development vector

项目摘要

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.

描述（由申请人提供）：该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用于基因疫苗接种的抗原方面的作用。将抗原掺入 Ad 衣壳是一种新颖且有前途的策略，可以利用 Ad 的免疫原性特性，也是规避预先存在的抗 Ad 免疫的一种方法。初步研究表明，最有希望将表位整合到Ad衣壳中的位点是纤维蛋白。总体假设是，即使在存在抗 Ad 免疫的情况下，在 Ad 纤维蛋白的最佳位置掺入表位也可以激发有效的保护性抗表位免疫。关于纤维修饰对抗原呈递和抗 Ad 免疫的影响知之甚少。关于纤维修饰对抗原呈递和抗 Ad 免疫的影响知之甚少。从拟议研究中获得的知识不仅可用于开发基于 Ad 的疫苗，还可以确定 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反应的假设。目标 2 将评估以下假设：源自两种细菌病原体的膜结合和分泌抗原的表位并入 Ad 纤维蛋白的最佳位置，可以在存在预先存在的抗 Ad 免疫的情况下诱导保护性免疫。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 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反应的潜力。正如这里提出的那样，疫苗的新方法将与公共卫生相关。它们可以帮助开发针对没有或没有好的疫苗的感染的疫苗。成功的疫苗对上个世纪的传染病预防产生了深远的影响。