Synthetic biology design to display an 18kDa rotavirus large antigen on a modular virus-like particle

Author(s)
Lua, Linda H L
Fan, Yuanyuan
Chang, Cindy
Connors, Natalie K
Middelberg, Anton P J
Publication Date
2015-11-04
Abstract
<p>Virus-like particles are an established class of commercial vaccine possessing excellent function and proven stability. Exciting developments made possible by modern tools of synthetic biology has stimulated emergence of modular VLPs, whereby parts of one pathogen are by design integrated into a less harmful VLP which has preferential physical and manufacturing character. This strategy allows the immunologically protective parts of a pathogen to be displayed on the most-suitable VLP. However, the field of modular VLP design is immature, and robust design principles are yet to emerge, particularly for larger antigenic structures. Here we use a combination of molecular dynamic simulation and experiment to reveal two key design principles for VLPs. First, the linkers connecting the integrated antigenic module with the VLP-forming protein must be well designed to ensure structural separation and independence. Second, the number of antigenic domains on the VLP surface must be sufficiently below the maximum such that a “steric barrier” to VLP formation cannot exist. This second principle leads to designs whereby co-expression of modular protein with unmodified VLP-forming protein can titrate down the amount of antigen on the surface of the VLP, to the point where assembly can proceed. In this work we elucidate these principles by displaying the 18.1 kDa VP8* domain from rotavirus on the murine polyomavirus VLP, and show functional presentation of the antigenic structure.</p>
Citation
Vaccine, 33(44), p. 5937-5944
ISSN
1873-2518
0264-410X
Pubmed ID
26387437
Link
Publisher
Elsevier Ltd
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Title
Synthetic biology design to display an 18kDa rotavirus large antigen on a modular virus-like particle
Type of document
Journal Article
Entity Type
Publication

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