CHIMPANZEES AND SUPPORTING MODELS IN THE STUDY OF MALARIA PREERYTHROCYTIC STAGES

Chimpanzees are being used in the study of immune response to Plasmodi um falciparum malaria pre-erythrocytic stages (MPES). Responses induce d by immunisation with recombinant/synthetic antigens and by irradiate d sporozoites are being evaluated in a model system that phylogenetica lly close close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees the in-depth study o f immunological mechanisms at work in MPES-induced protection are disc ussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged wi th large numbers of sporozoites, followed by surgical liver-wedge rese ction, in order to generate infected liver tissue for histological and immunological studies. As a complementary model SCID mice carrying li ve, transplanted human and primate hepatocytes have been inoculated wi th sporozoites and infection of transplanted cells has been monitored by histological and immunological methods, In ongoing experiments chim panzees are being immunised with MPES-derived lipopeptides that have b een shown to overcome MHC restriction in mice, and with irradiated spo rozoites.