The importance of human FcyRI in mediating protection to malaria
McIntosh, Richard S., Shi, Jianguo, Jennings, Richard M., Chappel, Jonathan C., de Koning-Ward, Tania, Smith, Tim, Green, Judith, van Egmond, Marjolein, Leusen, Jeanette H. W., Lazarou, Maria, van de Winkel, Jan, Jones, Tarran S., Crabb, Brendan S., Holder, Anthony A. and Pleass, Richard J. 2007, The importance of human FcyRI in mediating protection to malaria, PLoS pathogens, vol. 3, no. 5, pp. 647-658.
The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria. We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults. Although these novel reagents bind with strong affinity to malaria parasites, it remains unclear if in vitro assays are predictive of functional immunity in humans, due to the lack of suitable animal models permissive for P. falciparum. A potentially useful solution described herein allows the antimalarial efficacy of human antibodies to be determined using rodent malaria parasites transgenic for P. falciparum antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured animals of an otherwise lethal malaria infection, and protection was crucially dependent on human FcγRI. This important finding documents the capacity of FcγRI to mediate potent antimalaria immunity and supports the development of FcγRI-directed therapy for human malaria.
Field of Research
110803 Medical Parasitology
Socio Economic Objective
970111 Expanding Knowledge in the Medical and Health Sciences
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