Plant‐made dengue virus‐like particles produced by co‐expression of structural and non‐structural proteins induce a humoral immune response in mice

Ponndorf, Daniel; Meshcheriakova, Yulia; Thuenemann, Eva C.; Dobon Alonso, Albor; Overman, Ross; Holton, Nicholas; Dowall, Stuart; Kennedy, Emma; Stocks, Martin; Lomonossoff, George P.; Peyret, Hadrien

Abstract

Dengue virus (DENV) is an emerging threat causing an estimated 390 million infections per year. Dengvaxia, the only licensed vaccine, may not be adequately safe in young and seronegative patients; hence, development of a safer, more effective vaccine is of great public health interest. Virus-like particles (VLPs) are a safe and very efficient vaccine strategy, and DENV VLPs have been produced in various expression systems. Here, we describe the production of DENV VLPs in Nicotiana benthamiana using transient expression. The co-expression of DENV structural proteins (SP) and a truncated version of the non-structural proteins (NSPs), lacking NS5 that contains the RNA-dependent RNA polymerase, led to the assembly of DENV VLPs in plants. These VLPs were comparable in appearance and size to VLPs produced in mammalian cells. Contrary to data from other expression systems, expression of the protein complex prM-E was not successful, and strategies used in other expression systems to improve the VLP yield did not result in increased yields in plants but, rather, increased purification difficulties. Immunogenicity assays in BALB/c mice revealed that plant-made DENV1-SP + NSP VLPs led to a higher antibody response in mice compared with DENV-E domain III displayed inside bluetongue virus core-like particles and a DENV-E domain III subunit. These results are consistent with the idea that VLPs could be the optimal approach to creating candidate vaccines against enveloped viruses.

Citation

Ponndorf, D., Meshcheriakova, Y., Thuenemann, E. C., Dobon Alonso, A., Overman, R., Holton, N., Dowall, S., Kennedy, E., Stocks, M., Lomonossoff, G. P., & Peyret, H. (2021). Plant‐made dengue virus‐like particles produced by co‐expression of structural and non‐structural proteins induce a humoral immune response in mice. Plant Biotechnology Journal, 19(4), 745-756. https://doi.org/10.1111/pbi.13501

• Journal Article Type: Article
• Acceptance Date: Oct 20, 2020
• Online Publication Date: Nov 22, 2020
• Publication Date: 2021-04
• Deposit Date: Mar 5, 2025
• Publicly Available Date: Mar 5, 2025
• Journal: Plant Biotechnology Journal
• Print ISSN: 1467-7644
• Electronic ISSN: 1467-7652
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 4
• Pages: 745-756
• DOI: https://doi.org/10.1111/pbi.13501
• Public URL: https://nottingham-repository.worktribe.com/output/34350767
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/pbi.13501