INDUCTION OF OPSONIZING ANTIBODIES AFTER INJECTION OF RECOMBINANT PLASMODIUM-FALCIPARUM VACCINE CANDIDATE ANTIGENS IN PREIMMUNE SAIMIRI-SCIUREUS MONKEYS

We have previously shown that Plasmodium falciparum recombinant antige ns PfEB200, R23, and Pfi72 inhibit opsonization of infected erythrocyt es by hyperimmune Saimiri sera, indicating that they contain target ep itopes involved in the phagocytosis of infected erythrocytes. We have investigated in this study the immune response of Saimiri monkeys with previous experience of malaria infections (preimmune monkeys) after i njection of these recombinant antigens, administered alone or simultan eously. The humoral response to the recombinant antigens was monitored by radioimmunoassay, and the response to P. falciparum blood stages w as assayed by immunofluorescence. The relative proportion of protectiv e versus nonprotective immunoglobulin subtypes was investigated by usi ng 3A2/G6 and 3E4/H8 monoclonal antibodies, and the capacity of the an tisera to promote in vitro phagocytosis of infected erythrocytes was e valuated. The antigens evoked in most cases a secondary-type antibody response, resulting in important increases in antigen-specific antibod y titers and concomitantly in anti-P. falciparum titers. The ratio of 3A2/G6 to 3E4/H8 immunoglobulin subtypes varied with the immunogen use d. Opsonizing antibodies were boosted in several animals, the most pro mising combination being the mixture of PfEB200 and R23 that induced l ong-lasting production in five of five animals. The detectable opsoniz ing activity appearing after immunization of the animals was antigen s pecific, as it was lost after adsorption of the recombinant antigens. The challenge of the animals with blood stage parasites confirmed prev ious findings showing a correlation between the presence of detectable opsonizing antibodies in serum and protection.