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dc.contributor.authorStanisic, Danielle I
dc.contributor.authorFink, James
dc.contributor.authorMayer, Johanna
dc.contributor.authorCoghill, Sarah
dc.contributor.authorGore, Letitia
dc.contributor.authorLiu, Xue Q
dc.contributor.authorEl-Deeb, Ibrahim
dc.contributor.authorRodriguez, Ingrid B
dc.contributor.authorPowell, Jessica
dc.contributor.authorWillemsen, Nicole M
dc.contributor.authorDe, Sai Lata
dc.contributor.authorHo, Mei-Fong
dc.contributor.authorHoffman, Stephen L
dc.contributor.authorGerrard, John
dc.contributor.authorGood, Michael F
dc.date.accessioned2019-06-09T01:35:58Z
dc.date.available2019-06-09T01:35:58Z
dc.date.issued2018
dc.identifier.issn1741-7015
dc.identifier.doi10.1186/s12916-018-1173-9
dc.identifier.urihttp://hdl.handle.net/10072/383706
dc.description.abstractBackground: The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria. Methods: In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A. Results: We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected. Conclusions: This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofjournalBMC MEDICINE
dc.relation.ispartofvolume16
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode42
dc.titleVaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naive volunteers: a pilot study
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.rights.copyright© The Author(s). 2018 Open Access This article is 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 you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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gro.griffith.authorStanisic, Danielle
gro.griffith.authorGood, Michael F.
gro.griffith.authorEl-Deeb, Ibrahim Mustafa


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