title: Protection against malaria by immunization with non-attenuated sporozoites under single-dose piperaquine-tetraphosphate chemoprophylaxis.
abstract: Experimental whole-parasite immunization through concurrent administration of infectious Plasmodium sporozoites with drugs that prevent pathogenic blood-stage infection represents the current benchmark in malaria vaccine development. Key questions concerning translation remain, including the requirement for single-dose drug regimens that can reliably prevent breakthrough infections. We assessed the feasibility and efficacy of immunization with single-dose piperaquine chemoprophylaxis and concurrent sporozoite administration (PPQ-CPS) in the murine P. berghei ANKA/C57BL/6 infection model. We demonstrate that PPQ-CPS is protective with an efficacy comparable to previous findings using whole-parasite immunization under chloroquine chemoprophylaxis. PPQ-CPS immunization resulted in an expansion of intrahepatic and intrasplenic effector memory CD8(+) T cells. In summary, PPQ-CPS appears to be a safe and efficacious immunization regimen in the rodent malaria model and may thus become an important improvement regarding the translation of whole-parasite immunization toward a human malaria vaccine.
authors.affiliation: Department of Infectious Diseases, Parasitology Unit, University Hospital, Heidelberg, Germany; Center for Childhood and Adolescent Medicine, General Pediatrics, University Hospital, Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg, Germany. Electronic address: Johannes.Pfeil@med.uni-heidelberg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Pfeil
authors.affiliation: Department of Infectious Diseases, Parasitology Unit, University Hospital, Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg, Germany.
authors.forename: Katharina Jutta
authors.initials: KJ
authors.lastname: Sepp
authors.affiliation: Department of Infectious Diseases, Parasitology Unit, University Hospital, Heidelberg, Germany; MalVa GmbH, Heidelberg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Heiss
authors.affiliation: German Cancer Research Center (DKFZ), Department of Molecular Immunology (D050), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.affiliation: Department of Infectious Diseases, Parasitology Unit, University Hospital, Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mueller
authors.affiliation: German Center for Infection Research (DZIF), Tübingen, Germany; Institute for Tropical Medicine, University of Tübingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018890:Chemoprevention; D002738:Chloroquine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei; D011804:Quinolines / Q000627:therapeutic use*; D013154:Spleen / Q000276:immunology; D034101:Sporozoites / Q000276:immunology*; D010879:Piperazines
chemical_list: D002738:Chloroquine; D017780:Malaria Vaccines; D011804:Quinolines; C034759:piperaquine; D010879:Piperazines
keywords: Malaria; Malaria vaccination; Piperaquine; Piperaquine-tetraphosphate; Plasmodium; Whole-sporozoite immunization