Recent studies have shown that P. carinii (Pc) pneumonia (PCP) can be prevented by immunization with whole organisms in an immunosuppressed mouse model of disease. This raises the interesting possibility of trying to use this strategy to prevent disease in “at-risk” humans. However, because Pc cannot be cultured, immunization with whole organisms is not feasible. Therefore, we have undertaken studies to more precisely define the protective immune response to Pc with the hope of identifying the antigens responsible for confirming protection after immunization with whole organisms. Passive immunization with either monoclonal antibodies or sensitized lymphocytes have suggested that Pc gpA may be one such antigen. To directly assess the role of gpA in eliciting a protective immune response, we immunized mice with gpA, either in the form of nitrocellulose antigen bearing particles, or administered with the adjuvant Quil-A. Control animals received either immunization with whole organisms or with BSA. A gpA-specific response induced by either form of isolated gpA was equivalent to or exceeded that measured in the animals immunized with whole Pc. Immunization with gpA in the form of nitrocellulose antigen bearing particles induced a Th2-like antibody response, while Quil-A produced a mixed Th1/Th2-like antibody response. Table

Table 1 Characterization of the antibody response to Pc gpA
Full size table

Despite a strong antibody response to isolated gpA, the immunized mice were not protected. 28 of 37 (75%) of gpA-immunized mice developed PCP compared to only 3 of 12 (20%) whole Pc-immunized mice (p<0.001). These data do not support gpA as a significant target in the protective immune response to Pc and suggest that further studies are needed to define critical protective antigens of Pc.