dc.contributor.author | Stanisic, Danielle I | |
dc.contributor.author | Fink, James | |
dc.contributor.author | Mayer, Johanna | |
dc.contributor.author | Coghill, Sarah | |
dc.contributor.author | Gore, Letitia | |
dc.contributor.author | Liu, Xue Q | |
dc.contributor.author | El-Deeb, Ibrahim | |
dc.contributor.author | Rodriguez, Ingrid B | |
dc.contributor.author | Powell, Jessica | |
dc.contributor.author | Willemsen, Nicole M | |
dc.contributor.author | De, Sai Lata | |
dc.contributor.author | Ho, Mei-Fong | |
dc.contributor.author | Hoffman, Stephen L | |
dc.contributor.author | Gerrard, John | |
dc.contributor.author | Good, Michael F | |
dc.date.accessioned | 2019-06-09T01:35:58Z | |
dc.date.available | 2019-06-09T01:35:58Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1741-7015 | |
dc.identifier.doi | 10.1186/s12916-018-1173-9 | |
dc.identifier.uri | http://hdl.handle.net/10072/383706 | |
dc.description.abstract | Background:
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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.relation.ispartofjournal | BMC MEDICINE | |
dc.relation.ispartofvolume | 16 | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearch | Health sciences | |
dc.subject.fieldofresearchcode | 32 | |
dc.subject.fieldofresearchcode | 42 | |
dc.title | Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naive volunteers: a pilot study | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://creativecommons.org/licenses/by/4.0/ | |
dc.description.version | Version 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. | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Stanisic, Danielle | |
gro.griffith.author | Good, Michael F. | |
gro.griffith.author | El-Deeb, Ibrahim Mustafa | |