Basigin is a druggable target for host-oriented antimalarial interventions
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 an...
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2016
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| Online Access: | http://hdl.handle.net/1721.1/101120 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826190688133316608 |
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| author | Zenonos, Zenon A. Dummler, Sara K. Muller-Sienerth, Nicole Chen, Jianzhu Preiser, Peter R. Rayner, Julian C. Wright, Gavin J. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Zenonos, Zenon A. Dummler, Sara K. Muller-Sienerth, Nicole Chen, Jianzhu Preiser, Peter R. Rayner, Julian C. Wright, Gavin J. |
| author_sort | Zenonos, Zenon A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:44:11Z |
| format | Article |
| id | mit-1721.1/101120 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:44:11Z |
| publishDate | 2016 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1011202022-09-30T10:53:04Z Basigin is a druggable target for host-oriented antimalarial interventions Zenonos, Zenon A. Dummler, Sara K. Muller-Sienerth, Nicole Chen, Jianzhu Preiser, Peter R. Rayner, Julian C. Wright, Gavin J. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu 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. Wellcome Trust (London, England) (Grant 098051) Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology) 2016-02-05T15:17:02Z 2016-02-05T15:17:02Z 2015-07 2015-01 Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/101120 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. https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1084/jem.20150032 Journal of Experimental Medicine Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | Zenonos, Zenon A. Dummler, Sara K. Muller-Sienerth, Nicole Chen, Jianzhu Preiser, Peter R. Rayner, Julian C. Wright, Gavin J. Basigin is a druggable target for host-oriented antimalarial interventions |
| title | Basigin is a druggable target for host-oriented antimalarial interventions |
| title_full | Basigin is a druggable target for host-oriented antimalarial interventions |
| title_fullStr | Basigin is a druggable target for host-oriented antimalarial interventions |
| title_full_unstemmed | Basigin is a druggable target for host-oriented antimalarial interventions |
| title_short | Basigin is a druggable target for host-oriented antimalarial interventions |
| title_sort | basigin is a druggable target for host oriented antimalarial interventions |
| url | http://hdl.handle.net/1721.1/101120 https://orcid.org/0000-0002-5687-6154 |
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