Diverse mix of Human MoAbs to treat Anthrax exposure

描述（由申请人提供）：本申请的长期目标（I期和II期）是开发一种基于人单克隆抗体的制剂，用于治疗炭疽芽孢杆菌（炭疽）暴露或预防使用。这种制剂很可能由多种不同的单克隆抗体组成。这样的准备将填补可用于治疗这种生物战威胁的试剂库中的一个重大空白。

DESCRIPTION (provided by the applicant): The long-term goal of this proposal (phase I and II) is the development of a human monoclonal antibody-based preparation for use in treating B. anthracis (anthrax) exposure or for use prophylactically. This preparation would most likely be composed of multiple, different monoclonal antibodies. Such a preparation would fill a significant void in the arsenal of reagents available to treat this biowarfare threat. Phase I specific aims are: 1) Evaluate the human antibody response of peripheral blood leukocytes from AVA vaccinated donors in the human lymphocyte engrafted SCID mouse (hu-PBL-SCID system). Immunogens will include a) recombinant Protective Antigen (PA), b) the active fragment of PA, c) Lethal Factor (LF), and (optionally) d) the Lethal Toxin formed from PA+LF. Antigen specific serum human antibodies will be detected by 'ELISA, and neutralizing antibody levels will be measured using the murine macrophage cell line RAW. 2) Evaluate Lethal Toxin treatment as an in vivo approach to select mice making neutralizing antibodies. 3) Generate, from selected animals, an initial series of human monoclonal antibodies specific for PA, and possibly LF. These will be characterized for neutralizing activity, and using BIACORE, affinity and epitope grouping. The main goal of the phase II proposal will be the configuration of at least one combination of human monoclonals which could be evaluated in vivo for the ability to protect and/or rescue from B. anthracis challenge. The phase II SBIR program may require the generation of a larger panel of antibodies, based on the success of phase I.