Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/130894
Type: Thesis
Title: Hepatitis B core (HBc) virus like particle (VLP) as a platform for innovation of chimeric adjuvant-free VLP vaccines targeting oncoviruses
Author: Zhang, Bingyang
Issue Date: 2021
School/Discipline: School of Chemical Engineering and Advanced Materials
Abstract: Immunotherapy is an advanced technology for treatment of oncoviruses leading cancers. However, lack of effective and safe vaccines against the oncoviruses has limited the development. This thesis aims to apply Hepatitis B core (HBc) virus like particle (VLP) as a platform for innovation of chimeric adjuvant-free VLP vaccines targeting oncoviruses. Two chimeric HBc VLP-based vaccines presenting Epstein–Barr virus nuclear antigen 1 (EBNA1) epitope (short and non-structural epitope) and Hepatitis C virus (HCV) core epitope (long and structural epitope) were successfully expressed and purified in the Escherichia coli (E. coli) expression system with high production yields, 62.1 mg/g and 40.3 mg/g of wet cell weight, respectively. To further understand and evaluate the influence of insertion of different epitopes to HBc VLP, the stability of chimeric HBc VLP vaccines under different stresses were analysed in comparison with non-chimeric HBc VLP. Computational protein modelling was employed to assist the understanding of the possible cause for the differences. Results indicate that the stability of chimeric HBc VLP vaccines was related to the hydrophobicity of chimeric HBc monomers. The stability of chimeric HBc VLP decreased with the decrease of hydrophobicity of its monomer. This finding would help and improve the efficiency in the development and design of chimeric HBc VLP-based vaccines. In the immunogenicity evaluation, both adjuvant-free EBNA1-HBc VLP and HCV core-HBc VLP induced strong epitope-specific immune response in mice compared with other reported vaccine candidates of EBV and HCV. The achieved immune responses of adjuvant-free EBNA1-HBc VLP and HCV core-HBc VLP groups were comparable to the groups with aluminium adjuvant. No side effect and death of mice were detected during the examination. This confirms that adjuvant-free HBc VLP can present either short non-structured epitope or long structured epitope and can induce strong epitope-specific immune response with low safety risks. Chimeric EBNA1-HBc VLP tended to elicit predominated humoral immune response, while chimeric HCV core-HBc VLP induced predominated cellular immune response. This indicates that the nature of antigens presented by HBc VLP has an impact on the immune response performance, which should be considered in the design of chimeric HBc VLP vaccines in the future. The thesis also found that the addition of aluminium adjuvant would improve the humoral immune response while supressing the cellular immune response of chimeric HBc VLP vaccines. EBNA1-HBc VLP was less affected by the adjuvant on the immune response tendency compared with HCV core-HBc VLP. At last, long-term immunogenicity of two chimeric HBc VLPs were examined by evaluated the epitope specific memory T cells. Both HCV core-HBc VLP and EBAN1-HBc VLP showed good potential for long-term protection. With all above findings, chimeric adjuvant-free HBc VLP-based vaccine is promising to present different types of oncoviruses epitopes with high epitope-specific immune response and low risks. More epitopes targeting different oncoviruses could be presented by chimeric adjuvant-free HBc VLP platform for cancer treatment, and further computational protein modelling is helpful in the design and investigation of these novel chimeric HBc VLP-based vaccines.
Advisor: Bi, Jingxiu
Jiao, Yan
Su, Zhigou
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering and Advanced Materials, 2021
Keywords: Hepatitis B cor
virus like particle
protein purification
protein characterization
adjuvant-free
molecular dynamic simulation
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
Appears in Collections:Research Theses

Files in This Item:
File Description SizeFormat 
Zhang2021_PhD.pdf5.48 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.