Immunization with recombinant Pneumocystis carinii p55 antigen provides partial protection against infection: characterization of epitope recognitionassociated with immunization

Many therapeutic options exist for the treatment of Pneumocystis carinii pn eumonia, a common fungal opportunistic pulmonary pathogen, but treatment is often complicated by side effects and toxicity and, more recently, markers of drug resistance have been described. The development of immunotherapeti c modalities such as active immunization or passive immunotherapy may play an increasing important role in the prevention and treatment of infection. Passive immunotherapy with polyclonal anti-P. carinii reagents, such as ser um or T cells, and monospecific reagents reactive with the major surface gl ycoprotein (MSG or gpA), such as monoclonal antibodies or MSG primed T cell s, reduce the severity or eradicate infection. Active immunization with who le P. carinii, P. carinii extracts or MSG has afforded partial protection a gainst the subsequent development of P. carinii pneumonia in some animal mo dels. Identification of additional antigens with protective benefits will a id in the development of vaccines or other reagents. The p55 antigen of rat -derived P; carinii is well recognized by animals following natural exposur e to the organism. This 414 amino acid residue antigen found within the cel l wall of P, carinii contains 7 repeats of a glutamic acid-rich motif in th e carboxyl portion of the molecule. Both humoral and cellular immune respon ses reactive with this repeated domain are present following natural infect ion while, the amino terminal portion of the molecule is immunologically si lent. In this study, immunization with recombinant p55 elicited significant humoral and cellular immune responses which persisted during 10 weeks of i mmunosupression in corticosteroid treated rats; rp55 immunization resulted in a significant reduction in organism burden, improved histological. score , lower lung weight to body weight ratio (a marker of infection or lung inf lammation) and improved survival (P < 0.01). Greater protection was afforde d by immunization with a peptide containing amino acid residues 1-200, than by the entire rp55 molecule. Epitope recognition by serum from animals imm unized with rp55 differed from that of naturally exposed animals with oligo clonal responses to residues 22-92 and residues 196-218. This study demonst rates that protection against P. carinii can be afforded by immunization wi th antigen preparations other than whole extracts of P. carinii or the majo r surface antigen, MSG. This antigen moiety will likely be most useful as a vaccine candidate in combination with other immunogens which provide simil ar partial protection. (C) 2000 Editions scientifiques et medicales Elsevie r SAS.