P. carinii is an important pathogen in immnunocompromised hosts, including AIDS patients. We have utilized an animal model for establishing P. carinii infections in rats which have immunocompromised with dexamethasone. These animals exhibit a strong antibody production to a number of P. carinii proteins, most significantly to a major surface glycoprotein (MSG) of 120,000 MW. Several laboratories, including ours, have isolated cDNA clones coding for MSG. These clones code for a family of related but unique variants of MS(3. Comparison of the deduced amino acid sequences derived from these clones show that the variants contain conserved regions of high similarity and other regions of little similarity. We have recently demonstrated that several variants of MSG aide expressed in an infected animal, and that this expression pattern varied with time and location, suggesting that P. carinii may utilize a shift in MSG expression to evade the host response. It remains unclear, however, if the cellular or humoral response is directed at any of the regions which exhibit sequence conservation among the variants. This information would be of value in assessing the potential of using peptides as vaccines. A peptide epitope library was constructed using the deduced amino acid sequence of a full length MSG (GP3). Peptides of 15 amino acids in length were synthesized to span the entire 1066 amino acids of GP3. The peptides overlapped ten amino acids at their carboxy-termini. Using sera from immunocompromised rats, three peptides were consistently positive in ELISA. These peptides (two near the amino terminus and one near the carboxy terminus) were not ELISA positive using sera obtained.from these rats before they became infected. We are currently """"""""fine tuning"""""""" these peptides to determine the epitope more precisely. We will also obtain sera from rats at different locations to determine if the pattern of humoral response varies.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000099-03
Application #
3752162
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code