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dc.contributor.authorRaja, Amber I
dc.contributor.authorCai, Yeping
dc.contributor.authorReiman, Jennifer M
dc.contributor.authorGroves, Penny
dc.contributor.authorChakravarty, Sumana
dc.contributor.authorMcPhun, Virginia
dc.contributor.authorDoolan, Denise L
dc.contributor.authorCockburn, Ian
dc.contributor.authorHoffman, Stephen L
dc.contributor.authorStanisic, Danielle I
dc.contributor.authorGood, Michael F
dc.date.accessioned2018-07-16T04:51:35Z
dc.date.available2018-07-16T04:51:35Z
dc.date.issued2016
dc.identifier.issn0019-9567
dc.identifier.doi10.1128/IAI.00157-16
dc.identifier.urihttp://hdl.handle.net/10072/142909
dc.description.abstractThe 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrom2274
dc.relation.ispartofpageto2288
dc.relation.ispartofissue8
dc.relation.ispartofjournalInfection and Immunity
dc.relation.ispartofvolume84
dc.subject.fieldofresearchBiological Sciences not elsewhere classified
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchAgricultural and Veterinary Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode069999
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode07
dc.subject.fieldofresearchcode11
dc.titleChemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2016 Raja et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorGood, Michael F.
gro.griffith.authorRaja, Amber
gro.griffith.authorMcPhun, Virginia
gro.griffith.authorReiman, Jennifer M.
gro.griffith.authorStanisic, Danielle


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