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

• Main Authors: Wiebke Nahrendorf, Philip J Spence, Irene Tumwine, Prisca Lévy, William Jarra, Robert W Sauerwein, Jean Langhorne
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2015-02-01
• Series: eLife
• Subjects: malaria; vaccine; protection; sporozoite; cross-stage
• Online Access: https://elifesciences.org/articles/05165

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.