Multi-component and easily administrated anthrax vaccine

描述（由申请人提供）：炭疽是由孢子形成的细菌炭疽芽孢杆菌引起的，已经成为我国主要的生物恐怖威胁之一。在美国，获得许可的以保护性抗原（PA）为基础的疫苗，即吸附炭疽疫苗（AVA），需要进行六次免疫接种，然后每年加强一次。这强调了开发新的、改进的炭疽疫苗的必要性。本研究的长期目标是利用炭疽芽孢杆菌保护性抗原（PA63）、致死因子n端结构域（LFn，氨基酸1-254）和水肿因子（EFn，氨基酸1-254）作为疫苗组分，开发一种有效且易于给药的炭疽疫苗。我们的假设是一种有效的疫苗应该由多种相关抗原组成，通过鼻内途径递送，以提供针对炭疽的粘膜和全身免疫。将炭疽疫苗制成鼻喷雾剂将使大量人口在短时间内以较低的成本获得免疫。在目前可用的粘膜免疫策略中，用复制缺陷腺病毒递送抗原是一个很好的选择。本项目将构建重组腺病毒及编码PA63、LFn和EFn的质粒表达载体。为了评估疫苗的效果并提供最佳的疫苗接种方案，将不同腺病毒载体组合的鼻内免疫与肌内注射质粒表达载体的免疫进行比较。该项目的具体目标是：

DESCRIPTION (provided by applicant): Anthrax, which is caused by the spore-forming bacterium Bacillus anthracis, has become one of the major bioterrorism threats to our nation. Human vaccination in the USA with licensed protective antigen (PA)-based vaccine, Anthrax Vaccine Adsorbed (AVA), requires six immunizations followed by annual boosters. This underscores the need for development of new, improved anthrax vaccine. The long-term goal of this research is to develop an effective and easily administrated anthrax vaccine, using the B. anthracis protective antigen (PA63), the N-terminal domains of lethal factor (LFn, aminoacids 1-254) and edema factor (EFn, aminoacids 1-254) as vaccine components. Our hypothesis is that an effective vaccine should be composed of multiple relevant antigens delivered by an intranasal route in order to provide mucosal and systemic immunity against anthrax. Formulation of the anthrax vaccine into a nasal spray would allow a mass population to be immunized in a short period at a low cost. Among the currently available mucosal immunization strategies, antigen delivery with a replication-defective adenovirus is a good choice. Recombinant adenovirus and plasmid expression vectors encoding PA63, LFn and EFn will be constructed through this project. In order to evaluate the efficacy of the vaccine and provide an optimal vaccination protocol, intranasal immunization with different combinations of adenoviral vectors will be compared with immunization with plasmid expression vectors by intramuscular injection. The specific aims of this project are: Specific Aim #1: To develop a recombinant adenovirus-vectored multi-component vaccine against anthrax. Specific Aim #2: To compare the systemic and mucosal immunity elicited by the vaccine developed in #1 through intranasal inoculation with that elicited by plasmid expression vectors through intramuscular injection.