Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization
- University of Edinburgh, United Kingdom
- MRC National Institute for Medical Research, United Kingdom
- Radboud University Medical Center, Netherlands
- Cited 16
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Abstract
Protection against malaria in humans can be achieved by repeated exposure to infected mosquito bites during prophylactic chloroquine treatment (chemoprophylaxis and sporozoites (CPS)). We established a new mouse model of CPS immunization to investigate the stage and strain-specificity of malaria immunity. Immunization with Plasmodium chabaudi by mosquito bite under chloroquine cover does not generate pre-erythrocytic immunity, which is acquired only after immunization with high sporozoite doses. Instead, CPS immunization by bite elicits long-lived protection against blood-stage parasites. Blood-stage immunity is effective against a virulent, genetically distinct strain of P. chabaudi. Importantly, if exposure to blood-stage parasitemia is extended, blood-stage parasites induce cross-stage immunity targeting pre-erythrocytic stages. We therefore show that CPS immunization can induce robust, long-lived heterologous blood-stage immunity, in addition to protection against pre-erythrocytic parasites following high dose sporozoite immunization. Cross-stage immunity elicited by blood-stage parasites may further enhance efficacy of this immunization regimen.
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Ethics
Animal experimentation: All experiments were performed in accordance with UK Home Office regulations (PPL 80/2358) and approved by the ethical review panel at the MRC National Institute for Medical Research.
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Publication history
- Received: October 14, 2014
- Accepted: February 23, 2015
- Accepted Manuscript published: February 25, 2015 (version 1)
- Version of Record published: March 24, 2015 (version 2)
Copyright
© 2015, Nahrendorf et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Immunology and Inflammation
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- Immunology and Inflammation
