1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization

  1. Wiebke Nahrendorf
  2. Philip J Spence
  3. Irene Tumwine
  4. Prisca Lévy
  5. William Jarra
  6. Robert W Sauerwein
  7. Jean Langhorne  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. MRC National Institute for Medical Research, United Kingdom
  3. Radboud University Medical Center, Netherlands
Research Article
  • Cited 16
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Cite this article as: eLife 2015;4:e05165 doi: 10.7554/eLife.05165

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.

Article and author information

Author details

  1. Wiebke Nahrendorf

    Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Philip J Spence

    Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Irene Tumwine

    Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Prisca Lévy

    Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. William Jarra

    Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Robert W Sauerwein

    Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Jean Langhorne

    Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom
    For correspondence
    jlangho@nimr.mrc.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

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

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: October 14, 2014
  2. Accepted: February 23, 2015
  3. Accepted Manuscript published: February 25, 2015 (version 1)
  4. 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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