ANTHRAX VACCINE RESEARCH PROGRAM

炭疽疫苗研究计划

• 批准号: 7562520
• 负责人: ROBERT S MITTLER
• 金额: $ 3.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562520
• 关键词: Adverse effects; Adverse event; Aluminum Hydroxide; Anthrax Vaccines; Anthrax disease; Antibiotic Therapy; Antibodies; Antigens; Bacillus anthracis; Bacteria; Bioterrorism; Breathing; Cells; Computer Retrieval of Information on Scientific Projects Database; Condition; Development; Diagnosis; Disease; Dose; Edema; Encapsulated; Exotoxins; Frequencies; Funding; Grant; Human; IgG1; Immune response; Immune system; Immunity; Immunoglobulin G; Individual; Induration; Infection; Injection of therapeutic agent; Institution; Licensing; Localized; Macaca mulatta; Nature; Numbers; Organism; Population; Protocols documentation; Reaction; Recommendation; Reporting; Reproduction spores; Research; Research Personnel; Resources; Route; Series; Source; Time; Toxin; United States National Institutes of Health; Upper arm; Vaccinated; Vaccination; Vaccine Research; Vaccines; Week; anthrax lethal factor; edema factor; member; nonhuman primate; programs

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 炭疽芽孢杆菌，一种封装的形成孢子的细菌是炭疽病的病因。根据感染途径和诊断时间和适当的抗生素治疗，在超过90％的感染人群中，炭疽可能是致命的。 疾病和死亡是由于细菌分泌两种外毒素的能力而导致的。 这些二元毒素由保护性抗原和致命因子或保护性抗原和水肿因子组成。 这种生物体的孢子形成能力确保其在荒凉的条件下长期生存。 炭疽病在吸入孢子后引起致命感染使其成为生物恐怖主义的理想武器。 使用了吸收到氢氧化铝上的细菌培养物中的无细胞培养上清液，已开发出批准的针对炭疽的保护性疫苗，并称为吸附的炭疽疫苗或AVA。 目前，该疫苗作为六次注射量的武装部队成员。 免疫个体产生高滴度的IgG亚类抗体，特别是对三种毒素成分的活性中和活性的IgG1。 但是，已经发现，大量疫苗会经历不利的副作用，包括局部水肿和沉淀，这些疫苗可能被归类为严重，中度或轻度性质。 在某些情况下，已经报道了系统性反应。 尽管该疫苗已被许可使用了一段时间，并且自1990年以来已经给予了超过150万剂的剂量，但对人类对疫苗的免疫反应却很少，除了这样的事实，即保护性的体液免疫反应对疫苗中的exotoxins促进了exotoxins。 该协议的一个组成部分已开发出包括三组十一只恒河猴。 每组将在几个时间点（0、4周零6个月）的几个时间点接种不同浓度的批准的炭疽疫苗（炭疽疫苗吸附AVA）的疫苗接种。疫苗接种的管理路线和频率与当前的人类AVA系列建议不同。这项研究将不进行炭疽挑战。该提案的目的是详细分析免疫系统的细胞成分，这些细胞成分参与了对人类和非人类灵长类动物炭疽病的保护性免疫的发展。