dc.contributor.advisor |
Squire, C |
en |
dc.contributor.advisor |
Young, P |
en |
dc.contributor.author |
Saxby, Irene |
en |
dc.date.accessioned |
2020-03-26T02:36:47Z |
en |
dc.date.issued |
2020 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/50160 |
en |
dc.description |
Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Group A Streptococcus (GAS) infections can result in a multitude of health problems ranging from systemic invasive infections such as necrotising fasciitis to immune-mediated diseases, including acute rheumatic fever (ARF) and rheumatic heart disease (RHD). These health issues disproportionately affect people with lower socioeconomic status due to the effects of poverty and consequently are found at higher levels among Maori and Pasifika. Globally, the disease burden of GAS is high with over 34 million cases of RHD each year resulting in over 345,000 deaths. The development of a GAS vaccine, however, has long been impeded by high strain diversity as well as concerns they could trigger the very diseases a vaccine aims to reduce. The objective of this project was to develop a novel self-assembling GAS vaccine based on a protein scaffold which “glues” antigens together. Under specific conditions, these scaffold proteins ligate to each other via ester bond crosslinking to form a covalently linked stalk like structure. The antigens selected for display radiate from this trunk like the branches of a tree, such that we have named the designed vaccine “TreeVax”. TreeVax is a multivalent vaccine comprised of highly immunogenic pilin proteins from GAS. The bacterial pili are formed from the polymerisation of multiple copies of pilin proteins, referred to as T-antigens. These T-antigens elicit no known immune cross-reactivity with host tissues, and because they are present in multiple copies elicit a strong immune response. However, because of the high strain diversity and antigenic drift, an immunogenic response against a T-antigen from one strain is not necessarily protective against another. This is why a multivalent vaccine is needed to protect against the many circulating strains of GAS. We selected six T-antigens for our trial vaccine, T1, T5, T11, T12, T18.1 and T28.1, which include three of the most common strains found in NZ. Each of the selected T-antigens was expressed as a fusion protein with a self-assembling protein scaffold domain. When mixed, these fusion proteins spontaneously ligated together via the formation of ester bond cross-links between the “glue” domains, in a specific order and geometric arrangement to form an assembly that displays one copy of each T-antigen. As an extension of this in vitro work, an expression system was developed whereby the assembly of these larger vaccine structures takes place within the E. coli expression host. This in vivo expression, or auto-assembly of vaccine components has the potential to greatly simplify the production of multi-valent vaccines that are both economically viable and highly efficacious. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA |
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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 |
Restricted Item. Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
en |
dc.title |
A Scaffold Based Vaccine for Group A Streptococcus |
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dc.type |
Thesis |
en |
thesis.degree.discipline |
Biological Sciences |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.elements-id |
796991 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.record-created-at-source-date |
2020-03-26 |
en |
dc.identifier.wikidata |
Q112953711 |
|