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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AARR-C (02))
Program Officer
Duncan, Rory A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
Schools of Dentistry
United States
Zip Code
Cromwell, Elizabeth A; Stoddard, Steven T; Barker, Christopher M et al. (2017) The relationship between entomological indicators of Aedes aegypti abundance and dengue virus infection. PLoS Negl Trop Dis 11:e0005429
Tesini, Brenda L; Wright, Terry W; Malone, Jane E et al. (2017) Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii. Infect Immun 85:
Wells, Jesse; Haidaris, Constantine G; Wright, Terry W et al. (2006) Complement and Fc function are required for optimal antibody prophylaxis against Pneumocystis carinii pneumonia. Infect Immun 74:390-3
Wells, Jesse; Haidaris, Constantine G; Wright, Terry W et al. (2006) Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen. Infect Immun 74:2446-8
Gigliotti, Francis (2005) Pneumocystis carinii: has the name really been changed? Clin Infect Dis 41:1752-5
Gigliotti, Francis; Wright, Terry W (2005) Immunopathogenesis of Pneumocystis carinii pneumonia. Expert Rev Mol Med 7:1-16
Wells, Jesse; Gigliotti, Francis; Simpson-Haidaris, Patricia J et al. (2004) Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to Streptococcus pneumoniae surface antigen PspA. Infect Immun 72:1548-56
Empey, Kerry M; Hollifield, Melissa; Schuer, Kevin et al. (2004) Passive immunization of neonatal mice against Pneumocystis carinii f. sp. muris enhances control of infection without stimulating inflammation. Infect Immun 72:6211-20
Gigliotti, F; Harmsen, A G; Wright, T W (2003) Characterization of transmission of Pneumocystis carinii f. sp. muris through immunocompetent BALB/c mice. Infect Immun 71:3852-6
Koval, Christine E; Gigliotti, Francis; Nevins, Diana et al. (2002) Immune reconstitution syndrome after successful treatment of Pneumocystis carinii pneumonia in a man with human immunodeficiency virus type 1 infection. Clin Infect Dis 35:491-3

Showing the most recent 10 out of 41 publications