Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus.

The squirrel monkey Saimiri sciureus is one of the World Health Organization recommended experimental models of Plasmodium falciparum blood stage infection. Anti-malaria antibodies developed by this host after a drug-controlled infection play an important part in the acquired protection against the P. falciparum blood stages. Furthermore, the use of two anti-Saimiri immunoglobulin (Ig) monoclonal antibodies (mAb) has permitted the differentiation between protective (mAb 3A2/G6) and non-protective (mAb 3E4/H8) antibodies, as shown by transfer experiments to recipient monkeys infected with blood stage parasites. In the present study we have established that protection conferred by the 3A2/G6+ protective Ig preparation is strictly associated with an in vitro opsonic activity. Such an opsonic activity is not detectable in the 3E4/H8+ non-protective Ig population. In addition, results indicate that the 3E4/H8+ non-protective Ig population competes with protective opsonic 3A2/G6+ Ig antibodies when co-incubated with parasitized red blood cells. Thus, it follows that protection can be directly correlated to the quantitative and qualitative fluctuation of the two Ig populations. When challenged with 1 x 10(8) P. falciparum-infected Saimiri red blood cells parasitemia occurred in 5 out of 12 Saimiri who were lacking detectable 3A2/G6+ opsonic antibodies in their sera. By employing antibodies against the human Fc receptor for IgG (Fc gamma R) in an in vitro phagocytic assay, we have been able to show that the principal receptor is Fc gamma RIII. Finally, we also show that in contrast to the situation in man, this receptor is present on circulating monocytes. These findings could lead to a different strategy in designing malaria vaccine candidates and also allow the possibility of predicting the outcome of immunization trials in Saimiri monkeys.