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dc.contributor.authorGood, Michael F
dc.contributor.authorReiman, Jennifer M
dc.contributor.authorRodriguez, I Bibiana
dc.contributor.authorIto, Koichi
dc.contributor.authorYanow, Stephanie K
dc.contributor.authorEl-Deeb, Ibrahim M
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorStanisic, Danielle I
dc.contributor.authorEngwerda, Christian
dc.contributor.authorSpithill, Terry
dc.contributor.authorHoffman, Stephen L
dc.contributor.authorLee, Moses
dc.contributor.authorMcPhun, Virginia
dc.date.accessioned2017-05-03T12:53:56Z
dc.date.available2017-05-03T12:53:56Z
dc.date.issued2013
dc.date.modified2014-01-30T22:37:17Z
dc.identifier.issn0021-9738
dc.identifier.doi10.1172/JCI66634
dc.identifier.urihttp://hdl.handle.net/10072/56258
dc.description.abstractVaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with seco-cyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4+ T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1840388 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Clinical Investigation
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom3353
dc.relation.ispartofpageto3362
dc.relation.ispartofissue8
dc.relation.ispartofjournalJournal of Clinical Investigation
dc.relation.ispartofvolume123
dc.rights.retentionY
dc.subject.fieldofresearchInfectious agents
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchCellular immunology
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchcode310702
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320404
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode42
dc.titleCross-species malaria immunity induced by chemically attenuated parasites
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2013 American Society for Clinical Investigation (ASCI). The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorGood, Michael F.
gro.griffith.authorEl-Deeb, Ibrahim Mustafa
gro.griffith.authorStanisic, Danielle


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