Basigin is a druggable target for host-oriented antimalarial interventions
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Zenonos-2015-Basigin is a druggable.pdf
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Author(s)
Zenonos, Zenon A.
Dummler, Sara K.
Muller-Sienerth, Nicole
Chen, Jianzhu
Preiser, Peter R.
Rayner, Julian C.
Wright, Gavin J.
Date Issued
July 2015
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Zenonos, Z. A., S. K. Dummler, N. Muller-Sienerth, J. Chen, P. R. Preiser, J. C. Rayner, and G. J. Wright. “Basigin Is a Druggable Target for Host-Oriented Antimalarial Interventions.” Journal of Experimental Medicine 212, no. 8 (July 20, 2015): 1145–1151.
Version
Final published version
Abstract
Plasmodium falciparum is the parasite responsible for the most lethal form of malaria, an infectious disease that causes a large proportion of childhood deaths and poses a significant barrier to socioeconomic development in many countries. Although antimalarial drugs exist, the repeated emergence and spread of drug-resistant parasites limit their useful lifespan. An alternative strategy that could limit the evolution of drug-resistant parasites is to target host factors that are essential and universally required for parasite growth. Host-targeted therapeutics have been successfully applied in other infectious diseases but have never been attempted for malaria. Here, we report the development of a recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1 inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established P. falciparum blood-stage infection with no overt toxicity in an in vivo infection model. Collectively, our data demonstrate that antibodies or other therapeutics targeting host basigin could be an effective treatment for patients infected with multi-drug resistant P. falciparum.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1084/jem.20150032
