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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。炭疽芽孢杆菌是一种被包裹的孢子形成细菌，是炭疽的病原体。根据感染途径、诊断时间和适当的抗生素治疗，炭疽热在90%以上的感染人群中可能是致命的。细菌分泌两种外毒素的能力会导致疾病和死亡。这些二元毒素由保护性抗原和致死性因子，或保护性抗原和水肿因子组成。这种生物的孢子形成能力保证了它在恶劣条件下的长期生存。炭疽，在吸入其孢子后引起致命感染，使其成为生物恐怖主义的理想武器。一种经批准的针对炭疽的保护性疫苗是利用从细菌培养物中吸收到氢氧化铝上的无细胞培养上清液开发出来的，这种疫苗被称为吸附炭疽疫苗（AVA）。这种疫苗目前正在给武装部队成员注射，分六次注射。免疫个体产生高滴度的IgG亚类抗体，特别是IgG1，对三种毒素成分具有中和活性。然而，已发现相当数量的疫苗接种者出现不良副作用，包括局部水肿和硬结，其性质可分为严重、中度或轻度。在某些情况下，有全身反应的报道。尽管该疫苗获得使用许可已有一段时间，自1990年以来已接种了150多万剂疫苗，但除了对接种者体内的外毒素产生保护性体液免疫反应外，对该疫苗的人体免疫反应知之甚少。该方案的一个组成部分包括三组11只恒河猴。每组将在几个时间点（0、4周和6个月）接种不同浓度的经批准的炭疽疫苗（炭疽疫苗吸附AVA）。这种给药途径和疫苗接种频率不同于目前人类AVA系列的建议。本研究不进行炭疽挑战。本提案的目的是详细分析参与人类和非人类灵长类动物对炭疽产生保护性免疫的免疫系统的细胞成分。资金来源：nih