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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. (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). pp. 147-156. ISSN 0378-5173. (doi:10.1016/j.ijpharm.2017.03.001) (KAR id:78842)

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https://dx.doi.org/10.1016/j.ijpharm.2017.03.001

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.

Item Type: Article
DOI/Identification number: 10.1016/j.ijpharm.2017.03.001
Uncontrolled keywords: Gastrointestinal fluids, Gastrointestinal stability, HBcAg, Oral delivery, Proteins, VLPs, chymotrypsin, elastase, hepatitis B core antigen, pancreatin, pepsin A, sucrose, trypsin, epitope, hepatitis B surface antigen, virus like particle vaccine, acidification, agar gel electrophoresis, antigen expression, antigen purification, Article, carboxy terminal sequence, controlled study, drug stability, enzyme activity, ex vivo study, human, immunoreactivity, in vitro study, intestine fluid, mouse, Nicotiana benthamiana, nonhuman, pH, polyacrylamide gel electrophoresis, priority journal, stomach juice, sucrose gradient, transmission electron microscopy, ultracentrifugation, virus like agent, Western blotting, animal, body fluid, chemistry, drug stability, intestine, metabolism, oral drug administration, pig, plant, stomach, tobacco, Administration, Oral, Animals, Body Fluids, Drug Stability, Epitopes, Hepatitis B Surface Antigens, Intestines, Plants, Stomach, Sus scrofa, Swine, Tobacco, Vaccines, Virus-Like Particle, Medway School of Pharmacy
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Susan Barker
Date Deposited: 26 Nov 2019 16:28 UTC
Last Modified: 16 Jan 2020 12:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/78842 (The current URI for this page, for reference purposes)
Barker, Susan A.: https://orcid.org/0000-0003-4880-0253
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