Engineering viral capsomeres as a vaccine platform

Wibowo, Nani (2012). Engineering viral capsomeres as a vaccine platform PhD Thesis, Aust Institute for Bioengineering & Nanotechnology, The University of Queensland.

       
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Author Wibowo, Nani
Thesis Title Engineering viral capsomeres as a vaccine platform
School, Centre or Institute Aust Institute for Bioengineering & Nanotechnology
Institution The University of Queensland
Publication date 2012-01
Thesis type PhD Thesis
Supervisor Anton Middelberg
Linda Lua
Yap Pang Chuan
Total pages 164
Total colour pages 19
Total black and white pages 145
Language eng
Subjects 0904 Chemical Engineering
1003 Industrial Biotechnology
Formatted abstract
Influenza is a highly infectious respiratory disease caused by viruses from the family of Orthomyxoviridae. Vaccination against influenza remains a global challenge as the influenza viruses possess high mutation rates and occasionally re-emerge with distinctive shifted and drifted antigenic characteristics that render existing vaccines ineffective. Vaccine manufacturing based on a microbial platform holds potential to quickly and cost-effectively produce efficacious vaccines to counter the new emerging viruses. This thesis demonstrates the potential of microbially-synthesised murine polyomavirus capsomeres as a vaccine platform to present M2e antigen from influenza. The capsomere comprises five copies of VP1, which self assemble into a pentameric structure upon expression in Escherichia coli. M2e fused into VP1 was therefore rendered in a highly repetitive and orderly array suitable for efficient activation of antibody response. This research addressed the question specifically in the presentation of antigen on capsomere and the adjuvant formulation required for the induction of potent antibody response. The major outcomes of this work are: (i) demonstrating the limitation in chimeric VLPs assembly as a vaccine platform presenting M2e antigen, which then led to the need of an alternative platform such as capsomeres; (ii) understanding the robustness, safety, and immunogenicity of capsomeres as a vaccine platform to present M2e antigen; (iii) establishment of multiple copies presentation of M2e antigen on capsomere; and (iv) development of highly immunogenic formulation consisting of viral capsomeres mixed with non-adsorbing silica nanoparticles. This work introduces, to the best of our knowledge, the first multiple copy presentation of antigen on viral capsomeres. Presentation of M2e antigen in this capsomere format was shown to induce a greater than ten-fold antibody titre increase compared with administration of the peptide. This work also introduces a novel adjuvant formulation where non-adsorbing silica nanoparticles were used to adjuvant chimeric capsomeres through a simple mix prior to injection. The antibody levels induced were comparable to those induced by aluminium hydroxide-adjuvanted chimeric capsomeres. These findings suggest that attachment of immunogens onto nanoparticles is not necessary to gain adjuvanting efficacy, potentially circumventing the need for complex attachment approach widely used in the literature. More importantly, the level of anti-M2e antibodies induced from nanoparticles-adjuvanted chimeric capsomeres was comparable to those induced by vaccine candidates currently in clinical trial, indicating likely protective efficacy. These outcomes show the potential of viral capsomeres as a rapid-response and low-cost vaccine platform to target influenza virus.
Keyword Vaccine
Influenza
Escherichia coli
Murine polyomavirus
Virus-like particles
Capsomeres
Adjuvant
Nanoparticles
Nanoemulsion

 
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Created: Fri, 14 Sep 2012, 10:05:50 EST by Ms Nani Wibowo on behalf of Scholarly Communication and Digitisation Service