ANTHRAX VACCINE RESEARCH PROGRAM

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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.