title: Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice.
abstract: Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4+ T cells, IFN-gamma, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell responses against malaria as well as antigen availability for vaccine manufacture.
authors.affiliation: Molecular Immunology Laboratory and Australian Centre for Vaccine Development, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pinzon-Charry
authors.forename: Virginia
authors.initials: V
authors.lastname: McPhun
authors.forename: Vivian
authors.initials: V
authors.lastname: Kienzle
authors.forename: Chakrit
authors.initials: C
authors.lastname: Hirunpetcharat
authors.forename: Christian
authors.initials: C
authors.lastname: Engwerda
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D007376:Interleukin-2; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; D015164:Vaccines, Inactivated; D007371:Interferon-gamma