Journal article
Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes
J Healer, W Wong, JK Thompson, W He, RW Birkinshaw, K Miura, CA Long, V Soroka, TMM Søgaard, T Jørgensen, WA de Jongh, C Weir, E Svahn, PE Czabotar, WH Tham, I Mueller, PN Barlow, AF Cowman
Cellular Microbiology | WILEY | Published : 2019
DOI: 10.1111/cmi.13030
Abstract
An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF-7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C-terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a co..
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Awarded by United States Agency for International Development
Funding Acknowledgements
We thank Lin Chen for production of the CyRPA protein and Roma Galloway for assistance with protein production, the Victorian Red Cross Blood Bank for supply of blood and Simon Draper (Oxford University) for kindly supplying the anti-PfRh5 monoclonal antibody. Experimental data presented here were made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The research was supported by a National Health and Medical Research Council of Australia (NHMRC; GNT637406, GNT1020040, GNT1092789, GNT1117288, GNT1011453, GNT1057960). W. W. was supported through an Early Career Fellowship (1053801) from the NHMRC, and A. F. C. was an international scholar of the Howard Hughes Medical Institute (55007645). W. H. T. is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z). The GIA analysis performed at NIAID was supported in part by the Intramural Research Program of NIAID, NIH. We thank PATH/Malaria Vaccine Initiative and USAID for direct support.