Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection.

Autor:	Raja AI; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Cai Y; John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia., Reiman JM; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Groves P; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Chakravarty S; Sanaria, Inc., Rockville, Maryland, USA., McPhun V; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Doolan DL; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Cockburn I; John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia., Hoffman SL; Sanaria, Inc., Rockville, Maryland, USA., Stanisic DI; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Good MF; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia michael.good@griffith.edu.au.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2016 Jul 21; Vol. 84 (8), pp. 2274-2288. Date of Electronic Publication: 2016 Jul 21 (Print Publication: 2016).
DOI:	10.1128/IAI.00157-16
Abstrakt:	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. (Copyright © 2016 Raja et al.)
Databáze:	MEDLINE
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