Modular engineering of a microbially-produced viral capsomere vaccine for influenza

Wibowo, Nani, Chuan, Yap P., Lua, Linda H. L. and Middelberg, Anton P. J. (2012) Modular engineering of a microbially-produced viral capsomere vaccine for influenza. Chemical Engineering Science, 103 12-20. doi:10.1016/j.ces.2012.04.001

Author Wibowo, Nani
Chuan, Yap P.
Lua, Linda H. L.
Middelberg, Anton P. J.
Title Modular engineering of a microbially-produced viral capsomere vaccine for influenza
Journal name Chemical Engineering Science   Check publisher's open access policy
ISSN 0009-2509
Publication date 2012-04-06
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.ces.2012.04.001
Volume 103
Start page 12
End page 20
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Pergamon
Collection year 2013
Language eng
Abstract Faster and cheaper vaccine manufacture based on modern technologies is increasingly needed to effectively mitigate the burden of disease caused by highly contagious and mutagenic pathogens, such as influenza viruses. This study describes an approach to synthetically engineer a new influenza vaccine system by antigenic modularization of a carrier viral capsomere, coupled with microbial processing of the sub-unit vaccine. This approach leads to a system optimized with respect to both biological and process criteria. Murine polyomavirus VP1 protein, which self assembles into a pentameric sub-unit capsomere of a virus-like particle (VLP), was engineered to inhibit VLP assembly and to allow modular insertion of influenza M2e antigen at multiple sites within the protein. The yield, solubility, and immunogenicity of the resulting modular capsomeres could be optimized by varying the module insertion site and the number of M2e modules per site. This study demonstrated, for the first time, an innovative strategy of inserting multiple antigenic modules, up to 45 M2e modules, in a single capsomere. Modularization of M2e antigen was shown to improve its immunogenicity by more than an order of magnitude over that attained by immunization with an equivalent mass of non-modularized M2e peptide. Vaccination of mice using modular capsomeres induced high antigen-specific antibody levels suggestive of protective efficacy. This modular vaccine design approach, inspired by synthetic biology approaches to new system development, is conducive to technologies rapidly adaptable to pathogenic variations.
Keyword Synthetic biology
Virus-like particle
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online: 6 April 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Created: Mon, 15 Apr 2013, 13:06:20 EST by Julie Osborne on behalf of Aust Institute for Bioengineering & Nanotechnology