Plant‐made dengue virus‐like particles produced by co‐expression of structural and non‐structural proteins induce a humoral immune response in mice
| Autor: | Albor Dobon Alonso, Eva C. Thuenemann, Nicholas Holton, George P. Lomonossoff, Martin Stocks, Emma Kennedy, Hadrien Peyret, Ross Overman, Yulia Meshcheriakova, Daniel Ponndorf, Stuart D. Dowall |
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| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine viruses Protein subunit Nicotiana benthamiana Dengue Vaccines Plant Science Dengue virus Antibodies Viral medicine.disease_cause complex mixtures 01 natural sciences Virus transient expression Mice Viral Proteins 03 medical and health sciences Immune system bluetongue virus CLPs Viral envelope Tobacco medicine Animals Vaccines Virus-Like Particle Research Articles Mice Inbred BALB C dengue virus biology Flavivirus Immunogenicity virus diseases biochemical phenomena metabolism and nutrition antigen display biology.organism_classification Antibodies Neutralizing Virology Immunity Humoral 030104 developmental biology Agronomy and Crop Science virus‐like particles Research Article 010606 plant biology & botany Biotechnology |
| Zdroj: | Plant Biotechnology Journal |
| ISSN: | 1467-7652 1467-7644 |
| DOI: | 10.1111/pbi.13501 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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