Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria

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dc.contributor.authorBijker, Else M
dc.contributor.authorNganou-Makamdop, Krystelle
dc.contributor.authorvan Gemert, Geert-Jan
dc.contributor.authorZavala, Fidel
dc.contributor.authorCockburn, Ian
dc.contributor.authorSauerwein, Robert W
dc.date.accessioned2015-07-15T05:02:30Z
dc.date.available2015-07-15T05:02:30Z
dc.date.issued2015-03-26
dc.date.updated2015-12-08T11:00:48Z
dc.description.abstractBACKGROUND Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. METHODS A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8(+) T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. RESULTS When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8(+) T cells or CS protein-specific CD8(+) T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. CONCLUSIONS This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.
dc.description.sponsorshipEMB was supported by Top Institute Pharma (grant T4-102) and KN was supported by the NWO Mozaiek (grant no. 017.005.011).en_AU
dc.format10 pages
dc.identifier.issn1475-2875en_AU
dc.identifier.urihttp://hdl.handle.net/1885/14316
dc.publisherBioMed Central
dc.rights© 2015 Bijker et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.
dc.sourceMalaria Journal
dc.subjectChloroquine
dc.subjectSporozoite immunization
dc.subjectP. berghei
dc.subjectT cells
dc.subjectImmunity
dc.subjectProtection
dc.titleStudying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria
dc.typeJournal article
dcterms.dateAccepted2015-02-20
local.bibliographicCitation.issue1en_AU
local.bibliographicCitation.lastpage10
local.bibliographicCitation.startpage130en_AU
local.contributor.affiliationCockburn, I., John Curtin School of Medical Research, Australian National Universityen_AU
local.contributor.authoremailian.cockburn@anu.edu.auen_AU
local.contributor.authoruidu5289297en_AU
local.identifier.absfor110704 - Cellular Immunology
local.identifier.ariespublicationu9505948xPUB157
local.identifier.citationvolume14en_AU
local.identifier.doi10.1186/s12936-015-0626-2en_AU
local.identifier.essn1475-2875en_AU
local.identifier.scopusID2-s2.0-84926453425
local.identifier.uidSubmittedByu1005913en_AU
local.publisher.urlhttp://www.biomedcentral.com/en_AU
local.type.statusPublished Versionen_AU

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