Monoclonal Antibodies for the Study of P. carinii

描述（由申请人提供）：这个正在进行的研究项目的长期目标是利用单克隆抗体（mab）生产技术作为更好地了解卡氏疟原虫宿主-寄生虫相互作用的工具。我们对利用被动和主动免疫疗法预防或治疗卡氏杆菌肺炎（Pcp）特别感兴趣。在上一次拨款期间，我们展示了我们生产的一种单抗对Pcp具有显著的保护作用。此外，我们已经能够使用该单抗鉴定抗体识别的“保护性”表位，以及鉴定含有该感兴趣表位的两种卡氏疟原虫抗原（A12和KEX1）。根据我们迄今为止的进展，我们为这个项目提出了两个最重要的目标。我们的第一个目标是表征和利用这种保护性抗原-抗体相互作用，以开发预防Pcp的主动和被动免疫。我们的第二个目标是确定使用特异性抗体的被动免疫治疗对主动Pcp预后的影响，特别强调抗体对Pcp期间肺损伤免疫发病机制的影响。为实现这两个目标，我们提出以下具体目标：

DESCRIPTION (provided by applicant): This ongoing research project has had as its long-term goal utilizing the technology of monoclonal antibody (mab) production as a tool to better understand P. carinii host-parasite interactions. We are particularly interested in utilizing passive and active immunotherapy to prevent or treat P. carinii pneumonia (Pcp). During the last grant period we showed that one of the mab that we produced conferred significant protection against Pcp. Furthermore, we have been able to use that mab to identify the "protective" epitope recognized by the antibody as well as identifying two P. carinii antigens (A12 and KEX1) which contain this epitope of interest. Based on our progress to date, we propose two overriding goals for this project. Our first goal is to characterize and exploit this protective antigen-antibody interaction for the purpose of developing active and passive immunization for the prevention of Pcp. Our second goal is to define the effect of passive immunotherapy, with specific antibody, on the outcome of active Pcp with particular emphasis on the effect of antibody on the immunopathogenesis of lung injury during Pcp. To achieve these two goals we propose the following specific aims: 1) We will clone and characterize the complete cDNA of the gene encoding the A12 polypeptide and determine whether the A12 antigen is localized to the surface of P. carinii. 2) We will define the immunogenicity and efficacy of active immunization with recombinant antigens containing the epitopes recognized by mab 4F11. 3) We will examine the effect of passive antibody administration on established Pcp. Specifically, we will define the effect of passive antibody therapy on immune-mediated lung injury observed during Pcp. We will also determine the microbiologic effect of combining passive antibody therapy with conventional antimicrobial therapy.