Virus-like particles (VLPs) are elegant functional architectures formed by the self-assembly of viral structural proteins. VLPs have been developed as vaccines against hepatitis B and cervical cancer, and have recently been shown in animal studies to provide protection against both seasonal and avian influenza following intranasal administration. This new class of vaccines offers unprecedented immunoprotection, inherent safety, and a simple route of administration. To realize the full potential of VLP technology as an efficient and responsive vaccine platform, this project exploits the parallel advancements in recombinant technology, analytical techniques and colloidal science to facilitate the swift and economical delivery of candidate VLP vaccines from laboratory to clinical trials, and ultimately into commercial production. Three areas of VLP production are specifically targeted in this work, i.e., VLP subunit production, particle characterisation and assembly. The major research outcomes in this work are: (i) establishment of a simple and economical VLP subunit production method which eliminates inefficient and complicated purification procedures necessitated by the current in vivo production methods; (ii) development of a high-resolution and high-throughput analytical method for rapid and reliable quality control check of VLP products; and (iii) establishment of the foundation to predict optimal VLP self-assembly conditions through molecular thermodynamics. These research outcomes collectively enhance the quantitative knowledge base in VLP assembly and may ultimately enable the development of a mechanistic and descriptive modelling approach to optimize VLP production. From a fundamental perspective, this work introduces the first experimental technique to measure protein interactions of viral subunits undergoing rapid, irreversible assembly reaction. Such information, when correlated with molecular details and assembly conditions may provide unique insights into the molecular switches responsible for viral assembly, unveiling the fundamental mechanism underpinning viral self-assembly.
| Identifer | oai:union.ndltd.org:ADTP/279130 |
| Creators | Yap Chuan |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
Page generated in 0.0019 seconds