title: 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.
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Nahrendorf
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Spence
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Tumwine
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Prisca
authors.initials: P
authors.lastname: Lévy
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Jarra
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000276:immunology / Q000494:pharmacology; D018890:Chemoprevention / Q000379:methods; D002738:Chloroquine / Q000276:immunology* / Q000494:pharmacology; D009033:Culicidae / Q000276:immunology / Q000469:parasitology; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007303:Insect Vectors / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D034101:Sporozoites / Q000276:immunology*; D013997:Time Factors
chemical_list: D000962:Antimalarials; D002738:Chloroquine
keywords: cross-stage; immunology; infectious disease; malaria; microbiology; mouse; protection; sporozoites; vaccine