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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 炭疽芽孢杆菌是一种包膜孢子形成细菌，是炭疽病的病原体。根据感染途径、诊断时间和适当的抗生素治疗，炭疽可能对 90% 以上的感染人群致命。 由于细菌分泌两种外毒素的能力而导致疾病和死亡。 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。 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。 使用吸收到氢氧化铝上的细菌培养物的无细胞培养物上清液开发了一种经批准的炭疽保护性疫苗，称为吸附炭疽疫苗（AVA）。 目前，该疫苗正在为武装部队成员注射六次系列疫苗。 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具有中和活性的 IgG1。 然而，已发现相当多的疫苗接种者经历不良副作用，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，已有全身反应的报道。 尽管该疫苗已获得使用许可已有一段时间，并且自 1990 年以来已接种了超过 150 万剂疫苗，但除了对疫苗中的外毒素产生保护性体液免疫反应这一事实外，人们对该疫苗的人体免疫反应知之甚少。接种疫苗者。 该协议的一个组成部分已开发为包括三组，每组十一只恒河猴。 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与当前人类 AVA 系列建议不同。本研究不会进行炭疽攻击。该提案的目的是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。