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.
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