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Plant-expressed hepatitis B core antigen virus-like particles : characterization and investigation of their stability in simulated and pig gastro-intestinal fluids

Berardi, Alberto; Lomonossoff, George P.; Evans, David J.; Barker, Susan A.

Authors

Alberto Berardi

George P. Lomonossoff

David J. Evans

Susan A. Barker



Abstract

Virus-like particles (VLPs) are potential oral vaccine candidates, as their highly compact structure may allow them to withstand the harsh conditions of the gastro-intestinal (GI) environment. Hepatitis B core antigen (HBcAg) is an immunogenic protein that assembles into 30 or 34 nm diameter VLPs. Here, the stabilities of both the HBcAg polypeptide itself and the three-dimensional structure of the VLPs upon exposure to in vitro and ex vivo simulated gastric and intestinal fluids were investigated. Plant-expressed HBcAg VLPs were efficiently purified by sucrose density gradient and characterized. The purified VLPs did not show major chemical or physical instability upon exposure to the low pH conditions typically found in the stomach; however, they completely agglomerated upon acidification and subsequent pH neutralization. The HBcAg polypeptide was highly digested upon exposure to pepsin in simulated gastric fluids. HBcAg appeared more stable in both simulated and ex vivo intestinal fluids, where despite a partial digestion of the HBcAg polypeptide, the VLPs maintained their most immunogenic epitopes and their particulate conformation. These results suggest that HBcAg VLPs are likely to be unstable in gastric fluids, yet if the gastric instability could be bypassed, they could maintain their particulate structure and immunogenicity in intestinal fluids.

Citation

Berardi, A., Lomonossoff, G. P., Evans, D. J., & Barker, S. A. (2017). Plant-expressed hepatitis B core antigen virus-like particles : characterization and investigation of their stability in simulated and pig gastro-intestinal fluids. International Journal of Pharmaceutics, 522(1-2), 147-156. doi:10.1016/j.ijpharm.2017.03.001

Journal Article Type Article
Acceptance Date Mar 1, 2017
Online Publication Date Mar 2, 2017
Publication Date Apr 30, 2017
Deposit Date Mar 1, 2017
Publicly Available Date Mar 12, 2018
Journal International journal of pharmaceutics
Print ISSN 0378-5173
Electronic ISSN 1873-3476
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 522
Issue 1-2
Pages 147-156
DOI https://doi.org/10.1016/j.ijpharm.2017.03.001
Keywords Hepatitis B; HBcAg; VLPs; Oral delivery; Proteins; Gastrointestinal fluids; Gastrointestinal stability
Public URL https://hull-repository.worktribe.com/output/449075
Publisher URL http://www.sciencedirect.com/science/article/pii/S0378517317301680
Copyright Statement ©2018, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Additional Information Authors' accepted manuscript of article published in: International journal of pharmaceutics, 2017, v.522.

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