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dc.contributor.authorLee, Jason W
dc.contributor.authorParlane, Natalie A
dc.contributor.authorRehm, Bernd HA
dc.contributor.authorBuddle, Bryce M
dc.contributor.authorHeiser, Axel
dc.date.accessioned2018-02-16T01:00:26Z
dc.date.available2018-02-16T01:00:26Z
dc.date.issued2017
dc.identifier.issn0099-2240
dc.identifier.doi10.1128/AEM.02289-16
dc.identifier.urihttp://hdl.handle.net/10072/342849
dc.description.abstractTuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads that were produced in both Escherichia coli and Lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities, which we hypothesized to have the potential to induce immunity. In this study, we aimed to develop PHA beads produced in mycobacteria (mycobacterial PHA biobeads [MBB]) and test their potential as a TB vaccine in a mouse model. As a model organism, nonpathogenic Mycobacterium smegmatis was engineered to produce MBB or MBB with immobilized mycobacterial antigens Ag85A and ESAT-6 on their surface (A:E-MBB). Three key enzymes involved in the poly(3-hydroxybutyric acid) pathway, namely, β-ketothiolase (PhaA), acetoacetyl-coenzyme A reductase (PhaB), and PHA synthase (PhaC), were engineered into E. coli-Mycobacterium shuttle plasmids and expressed in trans. Immobilization of specific antigens to the surface of the MBB was achieved by creating a fusion with the PHA synthase which remains covalently attached to the polyester core, resulting in PHA biobeads displaying covalently immobilized antigens. MBB, A:E-MBB, and an M. smegmatis vector control (MVC) were used in a mouse immunology trial, with comparison to phosphate-buffered saline (PBS)-vaccinated and Mycobacterium bovis BCG-vaccinated groups. We successfully produced MBB and A:E-MBB and used them as vaccines to induce a cellular immune response to mycobacterial antigens.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrome02289-16-1
dc.relation.ispartofpagetoe02289-16-15
dc.relation.ispartofissue5
dc.relation.ispartofjournalApplied and Environmental Microbiology
dc.relation.ispartofvolume83
dc.subject.fieldofresearchApplied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies)
dc.subject.fieldofresearchcode320402
dc.titleEngineering mycobacteria for the production of self-assembling biopolyesters displaying mycobacterial antigens for use as a tuberculosis vaccine
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© 2017 Lee et al. This is an open-access article 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 the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorRehm, Bernd


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