IN-VIVO VERITAS - LESSONS FROM IMMUNOGLOBULIN-TRANSFER EXPERIMENTS INMALARIA PATIENTS

In most fields of medicine, experimentation starts with studies in vit ro, moves to animal models and eventually proceeds to research on huma ns. Malaria provides a good example of the limits of this progression. The most important malarial parasite of man, Plasmodium falciparum, o nly infects man. The specificity of this relationship accounts for the many differences which exist between artificial models of falciparum malaria and natural infections. Ultimately, human infections appear to be the sole, relevant 'model' for the study of human-Plasmodium inter actions. Immunoglobulin-transfer experiments, for example, clearly ind icated that antibodies mediated the state of acquired immunity called premunition. However, further studies in vitro or in animal models led to conflicting results about how the antibodies acted. Transfer exper iments in human volunteers, appropriately coupled to in-vitro studies, seemed the only way to help solve this issue. The design of these inv estigations, with its technical and ethical aspects, is reviewed here, along with the main published and unpublished results. The identifica tion of a monocyte-mediated, antibody-dependent (ADCI) mechanism led t o a new merozoite-surface antigen (MSP-3) being identified and provide d an explanation for the long delay in the acquisition of protection. It appears that experiments in humans not only help to confirm indicat ions obtained using animal models, but can also have a truly explorato ry role, since they can both raise completely new issues and provide a nswers to them.