An understanding of the relationship between malarial parasites and their hosts will ultimately aid in developing vaccine strategies. Malarial parasites release heat-stable soluble antigens into the sera of human infected with Plasmodium falciparum. The immunologic role of these antigens is unclear. We recently described a heat-stable antigen (Py117) that circulates in the sera of mice during Plasmodium yoelii infection and an immunologically-related, crossreactive protein (Pf93) that circulates in the sera of humans with P. falciparum malaria. Preliminary data suggest that soluble Py117 and an Ag of merozoites share common epitopes. This has led us to hypothesize that Py117 may provide a protective mechanism for the parasite by "tying-up antibodies before they reach important receptor molecules on the surface of merozoites. We also hypothesize that the secreted antigen is poorly immunogenic thereby increasing the probability of high levels of circulating antigen. These hypotheses will be tested using the P. yoelii-mouse model system. Experiments proposed include evaluating the antigenic relationship between the secreted and merozoite- associated forms of the antigen, determining if enhancing the immune response to Py117 by immunization or removal of immunoresponsiveness to Py117 by neonatal tolerance will alter the course of malaria infection, determining if the antibody response to Py117 is H-2 restricted and comparing the kinetics of antigenemia, anti-Py117 Ab production and possible formation of immune complexes in strains of mice that differ in susceptibility to malaria. Basic information gained from the mouse model should aid in our understanding of the human situation.

R22AI026153

1988-12-01

1991-11-30