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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, G S
dc.contributor.authorMargarit, Immaculada Y R
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorWalker, Mark J
dc.date.accessioned2012-12-12T13:45:51Z
dc.date.available2012-12-12T13:45:51Z
dc.date.issued2012-10
dc.identifier.citationConserved anchorless surface proteins as group A streptococcal vaccine candidates. 2012, 90 (10):1197-207 J. Mol. Med.en_GB
dc.identifier.issn1432-1440
dc.identifier.pmid22527883
dc.identifier.doi10.1007/s00109-012-0897-9
dc.identifier.urihttp://hdl.handle.net/10033/256296
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.language.isoenen
dc.rightsArchived with thanks to Journal of molecular medicine (Berlin, Germany)en_GB
dc.titleConserved anchorless surface proteins as group A streptococcal vaccine candidates.en
dc.typeArticleen
dc.contributor.departmentSchool of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.en_GB
dc.identifier.journalJournal of molecular medicine (Berlin, Germany)en_GB
refterms.dateFOA2018-06-12T22:06:40Z
html.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.


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