title: Chemically attenuated Plasmodium sporozoites induce specific immune responses, sterile immunity and cross-protection against heterologous challenge.
abstract: Vaccination with Plasmodium sporozoites attenuated by irradiation or genetic manipulation induces a protective immune response in rodent malaria models. Recently, vaccination with chemically attenuated P. berghei sporozoites (CAS) has also been shown to elicit sterile immunity in mice. Here we show that vaccination with CAS of P. yoelii also protects against homologous infection and that a P. berghei CAS vaccine cross protects against heterologous challenge with P. yoelii sporozoites. Vaccination with P. yoelii or P. berghei CAS induced parasite-specific antibodies and IFN-gamma-producing CD8(+) T cells at levels not significantly different from radiation-attenuated sporozoites. Our findings provide an initial characterization of the immune response generated by CAS vaccination and suggest that this attenuation process could be used in the production of an effective cross-protective liver stage vaccine for malaria.
authors.affiliation: McGill University, Institute of Parasitology and Centre for Host-Parasite Interactions, Sainte-Anne-de-Bellevue, QC, Canada.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Purcell
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Wong
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; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007211:Indoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D034101:Sporozoites / Q000187:drug effects / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007211:Indoles; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated; C527858:centanamycin; D007371:Interferon-gamma