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Early Plasma Cells as a Source of Anthrax-Neutralizing Antibodies

Early Plasma Cells as a Source of Anthrax-Neutralizing Antibodies
早期浆细胞作为炭疽中和抗体的来源
批准号:
7696156
负责人:
Patrick Christopher Wilson
金额:
$34.6万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-01 至 2014-08-31

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项目成果

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中文摘要
翻译
炭疽芽孢杆菌是高致病性的,因为它的孢子形式稳定,可以抵抗治疗
英文摘要
The bacterium Bacillus anthracis is highly pathogenic because of its stable spore form that resists treatment with antibiotics, its antiphagocytic capsule, and its production of potent toxins. Thus it has been studied as agent of biological warfare for some 60 years and is an extremely effective terrorist weapon. We have recently developed a novel strategy to rapidly produce fully human monoclonal antibodies after immunization and propose to use this technique to develop therapeutic antibodies against anthrax. These antibodies are derived recombinantly from expression of the immunoglobulin variable region genes of early antibodysecreting cells that arise in a massive, transient burst 7 days after immunization. This technology represents a substantial advance in monoclonal antibody production from humans and provides an opportunity to rapidly develop antibody therapies. We have now used this strategy to produce a limited number of antibodies from recipients of the anthrax vaccine. In collaboration with our U19 team we used serological studies to identify several key peptide epitopes that effectively neutralize anthrax toxin activity. The central goal of this Technology Component is to isolate the monoclonal antibodies that target these epitopes. These antibodies will be valuable as research and diagnostic reagents to assess protective immunity, and could ultimately be developed for safe passive immunization or for treatment of anthrax infection. In addition, analyses of monoclonal antibody reactivity may identify protective antibody specificities that are not dominant in the polyclonal response, or that only arise against non-peptide, structural epitopes. Although a vaccine against anthrax exists and is in limited use, primarily for vaccination of military personnel, its effectiveness is at best only "good". It requires multiple and continued boosts to provide protection, and our U19 group has determined that serum from only half of those immunized can neutralize anthrax toxicity. Thus a second goal of this component is to characterize the induction of long-term B cell immunity (memory) to gain insight into why the vaccine is relatively ineffective in inducing protective immunity.
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Exploring the mechanistic basis for altered peripheral B cell selection in SLE
  • 批准号:
    8732775
  • 项目类别:
  • 资助金额:
    $30.81万
  • 财政年份:
    2014
  • 负责人:
    Patrick Christopher Wilson
  • 依托单位:
Monoclonal Antibody Technology Core
Monoclonal Antibody Technology Core
COBRE: OK MED RES FOUND: P2: REGULATION OF ANTIBODY PRODUCTION TO A AUTOANTIGEN
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