Human malaria in immunocompromised mice: An in vivo model to study defensemechanisms against Plasmodium falciparum

We have recently described that sustained Plasmodium falciparum growth coul d be obtained in immunodeficient mice. We now report the potential of this new mouse model by assaying the effect of the passive transfer of antibodie s (Abs) which in humans have had a well-established effect. Our results show that the total African adult hyperimmune immunoglobulin Gs (HI-IgGs) strongly reduce P. falciparum parasitemia similarly to that repo rted in humans, but only when mice are concomitantly reconstituted with hum an monocytes (HuMNs). In contrast, neither HI-IgGs nor HuMNs alone had any direct effect upon parasitemia. We assessed the in vivo effect of epitope-s pecific human Abs affinity-purified on peptides derived either from the rin g erythrocyte surface antigen (RESA) or the merozoite surface protein 3 (MS P3). The inoculation of low concentrations of anti-synthetic peptide from M SP3, but not of anti-RESA Abs, consistently suppressed P. falciparum in the presence of HuMNs. Parasitemia decrease was stronger and faster than that observed using HI-IgGs and as fast as that induced by chloroquine. Our obse rvations demonstrate that this mouse model is of great value to evaluate th e protective effect of different Abs with distinct specificity in the same animal, a step hardly accessible and therefore never performed before in hu mans.