Group A Streptococcal Peptides expressed in HBsAg-S VLPs as a vaccine candidate

Piper, Stephanie J. (2014) Group A Streptococcal Peptides expressed in HBsAg-S VLPs as a vaccine candidate. Honours thesis, University of Southern Queensland. (Unpublished)

[img]
Preview
Text
Piper_BSci(Hons)_2014.pdf

Download (1291Kb) | Preview

Abstract

Streptococcus pyogenes, or Group A Streptococcus (GAS) is responsible for significant patient morbidity and mortality in the developing world and within the Australian Indigenous population. GAS is responsible for a variety of diseases such as invasive necrotizing fasciitis and toxic shock syndrome, as well as non-invasive diseases, such as pharyngitis, impetigo, scarlet fever and otitis media. However, GAS sequelae such as rheumatic fever and rheumatic heart disease are responsible for the highest morbidity. The 30-valent vaccine candidate currently
in trials is inappropriately specialised to serotypes present in areas with low GAS incidence, such as the United States.

The difficulty in creation of a suitable vaccine lies in part with the variety of GAS virulence factors. The M protein is a highly abundant, multifunctional immunogenic surface protein which confers resistance to phagocytes and complement mediated protection. As sections of the M
protein is highly conserved, it has been the focus of vaccination research. Furthermore, protein fragments J8 and J14 within the M protein have given encouraging results within a mouse model.

Virus-like particle (VLP) technology offers a promising alternative to existing vaccination delivery systems. VLPs are able to induce both cell mediated and humoral immune responses. In this study, the use of a chimeric hepatitis B surface antigen VLP expressing M
protein epitopes p145, J8 and J14 for use as a dual vaccine against Hepatitis B virus (HBV) and GAS is investigated. Specifically, PCR generated DNA sequences of J8, J14 and p145 from the M protein of GAS have been cloned into the highly immunogenic ‘a’ determinant region of the HBsAg-S VLP and transformed into human embryonic kidney (HEK293T) cells. Expressed recombinant HBsAg-S-GAS-m protein constructs were assayed by ELISA to confirm presentation of GAS epitopes. ELISA results showing high titres were obtained for VLP:p145 but low titres were obtained for VLP:J8 and VLP:J14. Further sequencing of plasmid constructs, protein expression and antigenic screening of proteins is required before the study can progress to proof-of-concept murine challenge models.


Statistics for USQ ePrint 27162
Statistics for this ePrint Item
Item Type: Thesis (Non-Research) (Honours)
Item Status: Live Archive
Additional Information: Bachelor of Science (Honours) thesis.
Faculty / Department / School: Current - Faculty of Health, Engineering and Sciences - School of Agricultural, Computational and Environmental Sciences
Supervisors: Kotiw, Mike; Seymour, Lisa
Date Deposited: 23 Apr 2015 05:52
Last Modified: 23 Apr 2015 05:52
Uncontrolled Keywords: Streptococcus pyogenes; Group A Streptococcus; vaccine candidate; HBsAg-S VLP
Fields of Research : 11 Medical and Health Sciences > 1107 Immunology > 110702 Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
11 Medical and Health Sciences > 1108 Medical Microbiology > 110804 Medical Virology
URI: http://eprints.usq.edu.au/id/eprint/27162

Actions (login required)

View Item Archive Repository Staff Only