title: Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection.
abstract: The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccine has not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. Here, we test chemically attenuated Plasmodium yoelii 17X and demonstrate significant protection following homologous and heterologous blood-stage challenge. Protection against blood-stage infection persisted for at least 9 months. Activation of both CD4(+) and CD8(+) T cells was shown after vaccination; however, in vivo studies demonstrated a pivotal role for both CD4(+) T cells and B cells since the absence of either cell type led to loss of vaccine-induced protection. In spite of significant activation of circulating CD8(+) T cells, liver-stage immunity was not evident. Neither did vaccine-induced CD8(+) T cells contribute to blood-stage protection; rather, these cells contributed to pathogenesis, since all vaccinated mice depleted of both CD4(+) and CD8(+) T cells survived a challenge infection. This study provides critical insight into whole-parasite vaccine-induced immunity and strong support for testing whole-parasite vaccines in humans.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Amber I
authors.initials: AI
authors.lastname: Raja
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Reiman
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Penny
authors.initials: P
authors.lastname: Groves
authors.affiliation: Sanaria, Inc., Rockville, Maryland, USA.
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Virginia
authors.initials: V
authors.lastname: McPhun
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Cockburn
authors.affiliation: Sanaria, Inc., Rockville, Maryland, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia michael.good@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D007114:Immunization; D007156:Immunologic Memory; D008018:Life Cycle Stages; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated