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dc.contributor.authorHenningham, Anna
dc.contributor.authorChiarot, Emiliano
dc.contributor.authorGillen, Christine M
dc.contributor.authorCole, Jason N
dc.contributor.authorRohde, Manfred
dc.contributor.authorFulde, Marcus
dc.contributor.authorRamachandran, Vidiya
dc.contributor.authorCork, Amanda J
dc.contributor.authorHartas, Jon
dc.contributor.authorMagor, Graham
dc.contributor.authorDjordjevic, Steven P
dc.contributor.authorCordwell, Stuart J
dc.contributor.authorKobe, Bostjan
dc.contributor.authorSriprakash, Kabada S
dc.contributor.authorNizet, Victor
dc.contributor.authorChhatwal, GS
dc.contributor.authorMargarit, Immaculada YR
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorWalker, Mark J
dc.date.accessioned2017-05-03T12:54:00Z
dc.date.available2017-05-03T12:54:00Z
dc.date.issued2012
dc.date.modified2012-12-21T02:28:41Z
dc.identifier.issn0946-2716
dc.identifier.doi10.1007/s00109-012-0897-9
dc.identifier.urihttp://hdl.handle.net/10072/48765
dc.description.abstractStreptococcus pyogenes (group A Streptococcus (GAS)) causes ~700 million human infections each year, resulting in over 500,000 deaths. The development of a commercial GAS vaccine is hampered by the occurrence of many unique GAS serotypes, antigenic variation within the same serotype, differences in serotype geographical distribution, and the production of antibodies cross-reactive with human tissue that may lead to autoimmune disease. Several independent studies have documented a number of GAS cell wall-associated or secreted metabolic enzymes that contain neither N-terminal leader sequences nor C-terminal cell wall anchors. Here, we applied a proteomic analysis of serotype M1T1 GAS cell wall extracts for the purpose of vaccine development. This approach catalogued several anchorless proteins and identified two protective vaccine candidates, arginine deiminase and trigger factor. These surface-exposed enzymes are expressed across multiple GAS serotypes exhibiting =99% amino acid sequence identity. Vaccine safety concerns are alleviated by the observation that these vaccine candidates lack human homologs, while sera from human populations suffering repeated GAS infections and high levels of autoimmune complications do not recognize these enzymes. Our study demonstrates anchorless cell surface antigens as promising vaccine candidates for the prevention of GAS disease.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.publisher.placeGermany
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1197
dc.relation.ispartofpageto1207
dc.relation.ispartofissue10
dc.relation.ispartofjournalJournal of Molecular Medicine
dc.relation.ispartofvolume90
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchBacteriology
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode310701
dc.titleConserved anchorless surface proteins as group A streptococcal vaccine candidates
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorBatzloff, Michael R.


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