Pneumocystis carinii is a classic opportunistic pathogen which produces a fatal pneumonia in patients with a variety of immunocompromising conditions, especially AIDS and cancer. Research in hte past few years shows that P. carinii pneumonia (PCP) can be prevented in a mouse model of disease by immunization with whole organisms. The hypothesis of this proposal is that PCP is a vaccine preventable disease. The availability of a mouse model of PCP whereby we can manipulate and study the immune response to P. carinii will allow us to more precisely define the host-parasite interactions involved in protection against PCP. The goal of this proposal is to identify those antigens which: 1) serve as the target for immune mediated clearance of P. carinii; and 2) are shared by human P. carinii. To achieve this goal, we propose to complete the follwoing specific aims:
Aim 1 : To produce and analyze monoclonal antibodies (Mab) to biologically relevant antigens of P. carinii;
Aim 2 : Toclone and characterize the cDNA encoding selected antigens identified by the Mab we isolate;
Aim 3 : To compare passive and active immunization utilizing monoclonal antibodies and antigens identified as being potentially important in the immune response to P. carinii with immunization using whole P. carinii;
and Aim 4 : To bridge the gap between our understanding of animal and human P.carinii by identifying conserved regions of mouse and human P. carinii antigens which can be used to generate data and develop reagents more directly relevant to human P. carinii. Information resulting from these experiments will serve to define the feasibility of using an immunologic approach to the control of PCP in immunocompromised humans.
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