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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Raja AI,Cai Y,Reiman JM,Groves P,Chakravarty S,McPhun V,Doolan DL,Cockburn I,Hoffman SL,Stanisic DI,Good MF

doi

10.1128/IAI.00157-16

subject

Has Abstract

pub_date

2016-07-21 00:00:00

pages

2274-2288

issue

8

eissn

0019-9567

issn

1098-5522

pii

IAI.00157-16

journal_volume

84

pub_type

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