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  • Title: Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection.
    Author: Raja AI, Cai Y, Reiman JM, Groves P, Chakravarty S, McPhun V, Doolan DL, Cockburn I, Hoffman SL, Stanisic DI, Good MF.
    Journal: Infect Immun; 2016 Aug; 84(8):2274-2288. PubMed ID: 27245410.
    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.
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