ANTHRAX VACCINE RESEARCH PROGRAM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。炭疽芽孢杆菌是一种有包囊的孢子形成细菌，是炭疽病的病原体。根据感染途径和诊断时间以及适当的抗生素治疗，炭疽可能在90%以上的感染人群中致命。疾病和死亡的发生是由于细菌分泌两种外毒素的能力。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。这种微生物的孢子形成能力保证了它在不适宜生存的条件下的长期生存。炭疽病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。一种被批准的针对炭疽的保护性疫苗已经被开发出来，使用的是来自细菌培养物的无细胞培养物上清液被吸附到氢氧化铝上，并被称为吸附炭疽疫苗，或AVA。这种疫苗目前正以六针一组的形式向武装部队成员提供。免疫个体产生高滴度的IgG亚类抗体，特别是对三种毒素组分具有中和活性的IgG 1。然而，已经发现，相当数量的疫苗接种者经历不良副作用，包括局部水肿和硬结，其可以被分类为严重、中度或轻度。在某些情况下，报告了全身反应。尽管该疫苗已被许可使用一段时间，自1990年以来已接种了150多万剂，但除了疫苗接种者对外毒素产生保护性体液免疫应答之外，对疫苗的人体免疫应答知之甚少。该方案的一个组成部分已开发为包括三组11只恒河猴。每组将在几个时间点（0、4周和6个月）接种不同浓度的获批炭疽疫苗（炭疽疫苗吸附AVA）。该接种途径和频率与当前人AVA系列建议不同。本研究将不进行炭疽菌攻毒。这项提议的目的是详细分析免疫系统的细胞成分，这些细胞成分参与人类和非人类灵长类动物对炭疽的保护性免疫的发展。资金来源：NIH

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