| Subpatent infection with nucleoside transporter 1-deficient Plasmodium blood stage parasites confers sterile protection against lethal malaria in mice. | |
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MedLine Citation:
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PMID: 20088947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Repeated immunizations with whole Plasmodium blood stage parasites and concomitant drug cure of infection confer protective immunity against parasite challenge in mice, monkeys and humans. Moreover, it was recently shown that infections with genetically modified rodent malaria blood stage parasites conferred sterile protection against lethal blood stage challenge. However, in these models vaccination resulted in high parasitemias and, in consequence, carries risk of vaccine-induced pathology and death. Herein, we generated a novel, completely blood stage-attenuated P. yoelii rodent malaria strain by targeted deletion of parasite nucleoside transporter 1 (NT1). Immunization of inbred and outbred mouse strains with a single low dose of Pynt1(-) blood stages did not induce any patent infections and conferred complete sterile protection against lethal heterologous blood stage and sporozoite challenges. Partial protection was observed against lethal challenges with another parasite species, P. berghei. Importantly, subcutaneous immunization with Pynt1(-) conferred sterile protection against lethal blood stage challenges. We show that cellular and humoral immune responses are both essential for sterile protection. The study demonstrates that genetic manipulation provides a platform for the designed, complete attenuation of malaria parasite blood stages and suggests testing the safety and efficacy of P. falciparum NT1 knockout strains in humans. |
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Authors:
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Ahmed S I Aly; Megan J Downie; Choukri Ben Mamoun; Stefan H I Kappe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-20 |
Journal Detail:
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Title: Cellular microbiology Volume: 12 ISSN: 1462-5822 ISO Abbreviation: Cell. Microbiol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-05 Completed Date: 2010-09-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883691 Medline TA: Cell Microbiol Country: England |
Other Details:
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Languages: eng Pagination: 930-8 Citation Subset: IM |
Affiliation:
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Seattle Biomedical Research Institute, Seattle, WA 98109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Female Malaria / immunology*, parasitology* Malaria Vaccines / genetics, immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Nucleoside Transport Proteins / genetics* Plasmodium / genetics, immunology* Plasmodium yoelii / genetics, immunology Protozoan Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Malaria Vaccines; 0/Nucleoside Transport Proteins; 0/Protozoan Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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