Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization

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

Wiebke Nahrendorf

Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom

Competing interests
The authors declare that no competing interests exist.
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.
Irene Tumwine

Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Prisca Lévy

Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
William Jarra

Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Robert W Sauerwein

Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands

Competing interests
The authors declare that no competing interests exist.
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

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

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.