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dc.contributor.authorTan, Aimee
dc.contributor.authorAtack, John M
dc.contributor.authorJennings, Michael P
dc.contributor.authorSeib, Kate L
dc.date.accessioned2019-02-04T01:30:29Z
dc.date.available2019-02-04T01:30:29Z
dc.date.issued2016
dc.identifier.issn1664-3224
dc.identifier.doi10.3389/fimmu.2016.00586
dc.identifier.urihttp://hdl.handle.net/10072/101094
dc.description.abstractInfectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression), are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase-variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFrontiers Research Foundation
dc.relation.ispartofpagefrom586-1
dc.relation.ispartofpageto586-9
dc.relation.ispartofissue586
dc.relation.ispartofjournalFrontiers in Immunology
dc.relation.ispartofvolume7
dc.subject.fieldofresearchInfectious agents
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchcode310702
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3105
dc.titleThe Capricious Nature of Bacterial Pathogens: Phasevarions and vaccine Development
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2016 Tan, Atack, Jennings and Seib. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
gro.hasfulltextFull Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorSeib, Kate
gro.griffith.authorAtack, John M.


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