The Importance of Human FcγRI in Mediating Protection to Malaria

PLoS Pathogens

Jeanette H. W Leusen¹  Marjolein van Egmond²  Jonathan C Chappel²  Richard M Jennings²  Brendan S Crabb³  Tarran S Jones⁴  Maria Lazarou⁴  Richard S McIntosh⁵  Judith Green⁵  Jianguo Shi⁵  Jan van de Winkel⁵  Anthony A Holder⁶  Tania F de Koning-Ward⁶  Richard J Pleass⁷  Tim Smith⁷ 

[1] Department of Molecular Cell Biology and Immunology, VU Medical Centre, Amsterdam, Netherlands;Division of Parasitology, National Institute for Medical Research, Medical Research Council, London, United Kingdom;Genmab, Utrecht, Netherlands;Immunotherapy Laboratory, Department of Immunology, University Medical Centre Utrecht, Utrecht, Netherlands;Institute of Genetics, Queen's Medical Centre, University of Nottingham, United Kingdom;Medical Research Council Technology, London, United Kingdom;Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

关键词: Plasmodium;    Malaria;    Antibodies;    Genetically modified animals;    Enzyme-linked immunoassays;    Parasitic diseases;    Mouse models;    Merozoites;   

DOI  :  10.1371/journal.ppat.0030072

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY