Conserved anchorless surface proteins as group A streptococcal vaccine candidates

Henningham, A; Chiarot, E; Gillen, CM; Cole, JN; Rohde, M; Fulde, M; Ramachandran, V; Cork, AJ; Hartas, J; Magor, G; Djordjevic, SP; Cordwell, SJ; Kobe, B; Sriprakash, KS; Nizet, V; Chhatwal, GS; Margarit, IYR; Batzloff, MR; Walker, MJ

Conserved anchorless surface proteins as group A streptococcal vaccine candidates

Henningham, A Chiarot, E Gillen, CM Cole, JN Rohde, M Fulde, M Ramachandran, V Cork, AJ Hartas, J Magor, G Djordjevic, SP

Cordwell, SJ Kobe, B Sriprakash, KS Nizet, V Chhatwal, GS Margarit, IYR Batzloff, MR Walker, MJ

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Publication Type:: Journal Article
Citation:: Journal of Molecular Medicine, 2012, 90 (10), pp. 1197 - 1207
Issue Date:: 2012-10-01

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Field	Value	Language
dc.contributor.author	Henningham, A	en_US
dc.contributor.author	Chiarot, E	en_US
dc.contributor.author	Gillen, CM	en_US
dc.contributor.author	Cole, JN	en_US
dc.contributor.author	Rohde, M	en_US
dc.contributor.author	Fulde, M	en_US
dc.contributor.author	Ramachandran, V	en_US
dc.contributor.author	Cork, AJ	en_US
dc.contributor.author	Hartas, J	en_US
dc.contributor.author	Magor, G	en_US
dc.contributor.author	Djordjevic, SP https://orcid.org/0000-0001-9301-5372	en_US
dc.contributor.author	Cordwell, SJ	en_US
dc.contributor.author	Kobe, B	en_US
dc.contributor.author	Sriprakash, KS	en_US
dc.contributor.author	Nizet, V	en_US
dc.contributor.author	Chhatwal, GS	en_US
dc.contributor.author	Margarit, IYR	en_US
dc.contributor.author	Batzloff, MR	en_US
dc.contributor.author	Walker, MJ	en_US
dc.date.available	2012-03-26	en_US
dc.date.issued	2012-10-01	en_US
dc.identifier.citation	Journal of Molecular Medicine, 2012, 90 (10), pp. 1197 - 1207	en_US
dc.identifier.issn	0946-2716	en_US
dc.identifier.uri	http://hdl.handle.net/10453/22051
dc.description.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 crossreactive 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. © Springer-Verlag 2012.	en_US
dc.relation.ispartof	Journal of Molecular Medicine	en_US
dc.relation.isbasedon	10.1007/s00109-012-0897-9	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Cell Wall	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Rabbits	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Streptococcus pyogenes	en_US
dc.subject.mesh	Streptococcal Infections	en_US
dc.subject.mesh	Hydrolases	en_US
dc.subject.mesh	Peptidylprolyl Isomerase	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Proteome	en_US
dc.subject.mesh	Recombinant Proteins	en_US
dc.subject.mesh	Immune Sera	en_US
dc.subject.mesh	Streptococcal Vaccines	en_US
dc.subject.mesh	Microscopy, Immunoelectron	en_US
dc.subject.mesh	Vaccination	en_US
dc.subject.mesh	Immunity, Active	en_US
dc.subject.mesh	Adolescent	en_US
dc.subject.mesh	Child	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Young Adult	en_US
dc.title	Conserved anchorless surface proteins as group A streptococcal vaccine candidates	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	90	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	90	en_US

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 crossreactive 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. © Springer-Verlag 2012.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/22051