The Journal of Experimental Medicine
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Published online 4 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1653/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1653-1660

Brief Definitive Report

Human Malaria in Immunocompromised Mice: An in Vivo Model to Study Defense Mechanisms against Plasmodium falciparum



Edgar Badella, Claude Oeuvraya, Alicia Morenoa, Soe Soea, Nico van Rooijenb, Ahmed Bouzidic, and Pierre Druilhea

a Bio-Medical Parasitology Unit, Institut Pasteur, 75015 Paris, France
b Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam 1081 BT, The Netherlands
c SEDAC-Therapeutics SA, 59000 Lille, France
Bio-Medical Parasitology Unit, Institut Pasteur 28, rue du Dr Roux, 75015 Paris, France.33-1-45-68-86-4033-1-45-68-85-78

druilhe{at}pasteur.fr

We have recently described that sustained Plasmodium falciparum growth could be obtained in immunodeficient mice. We now report the potential of this new mouse model by assaying the effect of the passive transfer of antibodies (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 reported in humans, but only when mice are concomitantly reconstituted with human monocytes (HuMNs). In contrast, neither HI-IgGs nor HuMNs alone had any direct effect upon parasitemia. We assessed the in vivo effect of epitope-specific human Abs affinity-purified on peptides derived either from the ring erythrocyte surface antigen (RESA) or the merozoite surface protein 3 (MSP3). The inoculation of low concentrations of anti-synthetic peptide from MSP3, 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 observations demonstrate that this mouse model is of great value to evaluate the protective effect of different Abs with distinct specificity in the same animal, a step hardly accessible and therefore never performed before in humans.

Key Words: mouse model • protective immunity • antibody-dependent cellular inhibition • merozoite surface protein 3 • ring erythrocyte surface antigen

© 2000 The Rockefeller University Press


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