ANTHRAX VACCINE RESEARCH PROGRAM

炭疽疫苗研究计划

• 批准号: 7349155
• 负责人: ROBERT S MITTLER
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349155
• 关键词: anthrax vaccines; antigens; culture; edema; human; immune response; infection; spores; toxin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bacillus anthracis, an encapsulated spore-forming bacterium is the causative agent of anthrax. Depending upon the route of infection and the time of diagnosis and proper antibiotic treatment, anthrax may be fatal in greater than 90% of the infected population. Disease and fatality occur as a result of the bacterium¿s ability to secrete two exotoxins. These binary toxins are composed of Protective Antigen and Lethal Factor, or Protective Antigen and Edema Factor. The spore-forming capacity of this organism assures its long-tem survival under inhospitable conditions. Anthrax, in causing lethal infection following the inhalation of its spores makes it an ideal weapon for bioterrorism. An approved protective vaccine against anthrax has been developed using cell-free culture supernatants from bacterial cultures absorbed onto aluminum hydroxide and termed Anthrax Vaccine Adsorbed, or AVA. This vaccine is currently being given to members of the armed forces as a series of six injections. Immunized individuals produce high titers of IgG subclass antibodies, in particular, IgG1 that have neutralizing activity against the three toxin components. However, it has been found that a significant number of vaccinees experience adverse side effects including localized edema and induration that may be classified as severe, moderate or mild in nature. In some cases systemic reactions have been reported. Despite the fact that the vaccine has been licensed for use for some time and over 1.5 million doses have been given since 1990 very little is known about the human immune response to the vaccine beyond the fact that a protective humoral immune response develops to the exotoxins in vaccinees. A component of this protocol has been developed to include three groups of eleven rhesus monkeys. Each group will be vaccinated with different concentrations of the approved anthrax vaccine (anthrax vaccine adsorbed AVA) at several time points (0, 4 weeks and 6 months). This administration route and frequency of vaccination differs from the current human AVA series recommendations. No anthrax challenge will be performed for this study. The intent of this proposal is to analyze in detail the cellular components of the immune system that participate in the development of protective immunity to anthrax in humans and non-human primates. FUNDING SOURCE: NIH

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。列出的是该中心，它不一定是炭疽杆菌的机构，一种封装的孢子形成细菌是炭疽病的病原体，具体取决于感染途径和炭疽杆菌。在诊断和适当的抗生素治疗后，超过 90% 的感染人群可能因炭疽病而死亡。其能够分泌两种外毒素。这些二元毒素由保护性抗原和致死因子或保护性抗原和水肿因子组成。该生物体的孢子形成能力确保了其在恶劣条件下的长期生存，从而导致致命感染。吸入其孢子后，它成为生物恐怖主义的理想武器，利用细菌的无细胞培养物上清液开发出一种经批准的炭疽保护性疫苗。吸附在氢氧化铝上的培养物被称为吸附炭疽疫苗（Anthrax Vaccine Adsorbed，AVA）。目前，该疫苗通过六次注射的方式向武装部队成员注射，产生高滴度的 IgG 亚类抗体，特别是具有中和作用的 IgG1。然而，已发现大量疫苗会出现不良副作用，包括局部水肿和硬结，这些副作用可分为严重、中度或轻度。尽管该疫苗已获准使用一段时间，并且自 1990 年以来已接种超过 150 万剂，但在某些情况下，人们对疫苗的免疫反应知之甚少。该方案的一个组成部分是对接种者体内的外毒素产生保护性体液免疫反应，其中包括三组，每组 11 只恒河猴，每组将接种不同浓度的经批准的炭疽疫苗（炭疽疫苗）。吸附 AVA）在几个时间点（0、4 周和 6 个月）这种接种途径和疫苗接种频率与当前的人类 AVA 系列建议不同。详细分析参与人类和非人类灵长类动物炭疽保护性免疫发展的免疫系统的细胞成分。