dc.contributor.author |
Moreland, Nicole |
en |
dc.contributor.author |
Raynes, Jeremy |
en |
dc.contributor.author |
Hughes, Jacelyn |
en |
dc.contributor.author |
Proft, Thomas |
en |
dc.contributor.author |
Baker, Edward |
en |
dc.contributor.author |
Young, Paul |
en |
dc.date.accessioned |
2019-10-01T03:11:56Z |
en |
dc.date.issued |
2019-06 |
en |
dc.identifier.issn |
0019-9567 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/48205 |
en |
dc.description.abstract |
Group A Streptococcus (GAS) (Streptococcus pyogenes) is an important human pathogen associated with significant global morbidity and mortality for which there is no safe and efficacious vaccine. The T antigen, a protein that polymerizes to form the backbone of the GAS pilus structure, is a potential vaccine candidate. Previous surveys of the tee gene, which encodes the T antigen, have identified 21 different tee types and subtypes such that any T antigen-based vaccine must be multivalent and carefully designed to provide broad strain coverage. In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The existence of shared epitopes between T antigens, combined with the remarkably conserved structure and high level of surface sequence divergence, has important implications for the design of multivalent T antigen-based vaccines. |
en |
dc.format.medium |
Electronic-Print |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Infection and immunity |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Animals |
en |
dc.subject |
Rabbits |
en |
dc.subject |
Humans |
en |
dc.subject |
Streptococcus pyogenes |
en |
dc.subject |
Streptococcal Infections |
en |
dc.subject |
Streptococcal Vaccines |
en |
dc.subject |
Antibodies, Bacterial |
en |
dc.subject |
Antigens, Bacterial |
en |
dc.subject |
Cross Reactions |
en |
dc.title |
Group A Streptococcus T Antigens Have a Highly Conserved Structure Concealed under a Heterogeneous Surface That Has Implications for Vaccine Design. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1128/IAI.00205-19 |
en |
pubs.issue |
6 |
en |
pubs.volume |
87 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
773483 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1098-5522 |
en |
pubs.record-created-at-source-date |
2019-04-03 |
en |
pubs.dimensions-id |
30936156 |
en |