Multi-component and easily administrated anthrax vaccine

描述（由申请人提供）：炭疽，这是由孢子形成细菌炭疽杆菌引起的，已成为我国主要的生物恐怖主义威胁之一。在美国，使用许可的基于保护性抗原（PA）的疫苗（吸附炭疽疫苗（AVA））的人类疫苗接种需要六次免疫接种，然后每年加强一次。这突出表明需要开发新的、改进的炭疽疫苗。本研究的长期目标是利用B开发一种有效且易于管理的炭疽疫苗。炭疽保护性抗原（PA 63）、致死因子（LFn，氨基酸1-254）和水肿因子（EFn，氨基酸1-254）的N-末端结构域作为疫苗组分。我们的假设是，一个有效的疫苗应该由多种相关抗原通过鼻内途径提供，以提供粘膜和全身免疫炭疽。将炭疽疫苗制成鼻喷雾剂将使大规模人口在短时间内以低成本获得免疫。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。本项目将构建编码PA 63、LFn和EFn的重组腺病毒和质粒表达载体。为了评价疫苗的效力并提供最佳的疫苗接种方案，将比较用腺病毒载体的不同组合进行的鼻内免疫与通过肌内注射用质粒表达载体进行的免疫。 该项目的具体目标是： 具体目标#1：开发针对炭疽的重组腺病毒载体多组分疫苗。 具体目标#2：比较#1中开发的疫苗通过鼻内接种与质粒表达载体通过肌内注射引发的全身和粘膜免疫。

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.