Multi-component and easily administrated anthrax vaccine

描述(申请人提供)：由炭疽芽孢杆菌引起的炭疽病已成为我国生物恐怖主义的主要威胁之一。在美国，人类接种以获得许可的保护性抗原(PA)为基础的疫苗--吸附炭疽疫苗(AVA)--需要进行六次免疫接种，然后每年接种一次。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以炭疽杆菌保护性抗原(PA63)、致死因子N端区(LFN，氨基酸1-254)和水肿区(EFN，氨基酸1-254)为疫苗成分，研制一种有效且易于管理的炭疽疫苗。我们的假设是，一种有效的疫苗应该由多个相关抗原组成，通过鼻腔途径输送，以提供对炭疽病的粘膜和系统免疫。将炭疽疫苗制成鼻腔喷雾剂将允许在短时间内以低成本为大量人口接种疫苗。在目前可用的粘膜免疫策略中，用复制缺陷型腺病毒递送抗原是一个很好的选择。通过该项目将构建编码PA63、LFN和EFN的重组腺病毒和表达载体。为了评价疫苗的免疫效果和提供最佳的免疫方案，将不同组合的腺病毒载体鼻腔免疫和肌肉注射表达载体的疫苗进行了比较。该项目的具体目标是： 具体目的1：研制一种重组腺病毒载体多组分炭疽疫苗。 具体目的#2：比较1号疫苗鼻腔接种与质粒表达载体肌肉注射诱导的全身和粘膜免疫。

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.