title: Chemical attenuation of Plasmodium berghei sporozoites induces sterile immunity in mice.
abstract: Radiation and genetic attenuation of Plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits Plasmodium falciparum growth in vitro. Here we show that treatment of Plasmodium berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective liver stage vaccine for malaria.
authors.affiliation: Institute of Parasitology and Centre for Host-Parasite Interactions, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Quebec H9X3V9, Canada.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Purcell
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Yanow
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
authors.forename: Terry W
authors.initials: TW
authors.lastname: Spithill
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005260:Female; D022781:Hepatocytes / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000517:prevention & control; D010962:Plasmodium berghei / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D016052:Protozoan Vaccines / Q000276:immunology*; D034101:Sporozoites / Q000187:drug effects* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000981:Antiprotozoal Agents; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated