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dc.contributor.authorReiman, Jennifer M
dc.contributor.authorKumar, Sanjai
dc.contributor.authorRodriguez, Ingrid B
dc.contributor.authorGnidehou, Sedami
dc.contributor.authorIto, Koichi
dc.contributor.authorStanisic, Danielle I
dc.contributor.authorLee, Moses
dc.contributor.authorMcPhun, Virginia
dc.contributor.authorMajam, Victoria
dc.contributor.authorWillemsen, Nicole M
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorRaja, Amber I
dc.contributor.authorDooley, Brad
dc.contributor.authorHoffman, Stephen L
dc.contributor.authorYanow, Stephanie K
dc.contributor.authorGood, Michael F
dc.date.accessioned2019-05-29T13:04:48Z
dc.date.available2019-05-29T13:04:48Z
dc.date.issued2018
dc.identifier.issn2050-0068
dc.identifier.doi10.1002/cti2.1015
dc.identifier.urihttp://hdl.handle.net/10072/379940
dc.description.abstractObjectives: Blood stage malaria parasites attenuated with seco‐cyclopropyl pyrrolo indole (CPI) analogues induce robust immunity in mice to homologous and heterologous malaria parasites and are being considered for the development of a human vaccine. However, it is not understood how attenuated parasites induce immunity. We showed that following vaccination, parasite DNA persisted in blood for several months, raising the possibility that ongoing immune stimulation may be critical. However, parasites were not seen microscopically beyond 24 h postvaccination. We aimed to provide a mechanistic understanding of immune induction. Methods: Mice were vaccinated with chemically attenuated Plasmodium chabaudi parasites. PCR and adoptive transfer studies were used to determine the presence of parasites and antigen in vivo. In other experiments, Plasmodium falciparum parasitised red blood cells were attenuated in vitro and RNA and antigen expression studied. Results: We show that blood transferred from vaccinated mice into naïve mice activates T cells and induces complete protective immunity in the recipient mice strongly suggesting that there is persistence of parasite antigen postvaccination. This is supported by the presence of parasite RNA in vaccinated mice and both RNA and antigen expression in P. falciparum cultures treated with CPI drugs in vitro. In addition, drugs that block parasite growth also prevent the induction of immunity in vaccinated mice, indicating that some growth of attenuated parasites is required for immune induction. Conclusions: Attenuated parasites persist at submicroscopic levels in the blood of mice postvaccination with the ability to activate T cells and induce ongoing protective immune responses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherJohn Wiley & Sons
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto13
dc.relation.ispartofissue4
dc.relation.ispartofjournalClinical & Translational Immunology
dc.relation.ispartofvolume7
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchcode110799
dc.titleInduction of immunity following vaccination with a chemically attenuated malaria vaccine correlates with persistent antigenic stimulation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc/4.0/
dc.description.versionPublished
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2018 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
gro.hasfulltextFull Text
gro.griffith.authorBatzloff, Michael R.
gro.griffith.authorWillemsen, Nicole M.
gro.griffith.authorGood, Michael F.
gro.griffith.authorIto, Koichi
gro.griffith.authorRodríguez Guzmán, Ingrid B.
gro.griffith.authorDooley, Brad
gro.griffith.authorRaja, Amber
gro.griffith.authorMcPhun, Virginia
gro.griffith.authorReiman, Jennifer M.
gro.griffith.authorStanisic, Danielle


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