2.50
Hdl Handle:
http://hdl.handle.net/10033/256296
Title:
Conserved anchorless surface proteins as group A streptococcal vaccine candidates.
Authors:
Henningham, Anna; Chiarot, Emiliano; Gillen, Christine M; Cole, Jason N; Rohde, Manfred; Fulde, Marcus; Ramachandran, Vidiya; Cork, Amanda J; Hartas, Jon; Magor, Graham; Djordjevic, Steven P; Cordwell, Stuart J; Kobe, Bostjan; Sriprakash, Kabada S; Nizet, Victor; Chhatwal, G S; Margarit, Immaculada Y R; Batzloff, Michael R; Walker, Mark J
Abstract:
Streptococcus 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.
Affiliation:
School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
Citation:
Conserved anchorless surface proteins as group A streptococcal vaccine candidates. 2012, 90 (10):1197-207 J. Mol. Med.
Journal:
Journal of molecular medicine (Berlin, Germany)
Issue Date:
Oct-2012
URI:
http://hdl.handle.net/10033/256296
DOI:
10.1007/s00109-012-0897-9
PubMed ID:
22527883
Type:
Article
Language:
en
ISSN:
1432-1440
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorHenningham, Annaen_GB
dc.contributor.authorChiarot, Emilianoen_GB
dc.contributor.authorGillen, Christine Men_GB
dc.contributor.authorCole, Jason Nen_GB
dc.contributor.authorRohde, Manfreden_GB
dc.contributor.authorFulde, Marcusen_GB
dc.contributor.authorRamachandran, Vidiyaen_GB
dc.contributor.authorCork, Amanda Jen_GB
dc.contributor.authorHartas, Jonen_GB
dc.contributor.authorMagor, Grahamen_GB
dc.contributor.authorDjordjevic, Steven Pen_GB
dc.contributor.authorCordwell, Stuart Jen_GB
dc.contributor.authorKobe, Bostjanen_GB
dc.contributor.authorSriprakash, Kabada Sen_GB
dc.contributor.authorNizet, Victoren_GB
dc.contributor.authorChhatwal, G Sen_GB
dc.contributor.authorMargarit, Immaculada Y Ren_GB
dc.contributor.authorBatzloff, Michael Ren_GB
dc.contributor.authorWalker, Mark Jen_GB
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.en_GB
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

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