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The importance of human FcyRI in mediating protection to malaria

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journal contribution
posted on 2007-01-01, 00:00 authored by R McIntosh, J Shi, R Jennings, J Chappel, Tania De Koning-WardTania De Koning-Ward, T Smith, J Green, M van Egmond, J Leusen, M Lazarou, J van de Winkel, T Jones, B Crabb, A Holder, R Pleass
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.

History

Journal

PLoS pathogens

Volume

3

Pagination

647 - 658

Location

San Francisco, CA

Open access

  • Yes

ISSN

1553-7366

eISSN

1553-7374

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal; C Journal article

Copyright notice

2007, Public Library of Science