Development and characterization of a plant-derived rotavirus-like particle vaccine

• Published in: Vaccine Vol. 39; no. 35; pp. 4979 - 4987
• Main Authors: Kurokawa, Natsuki, Lavoie, Pierre-Olivier, D'Aoust, Marc-André, Couture, Manon M.-J., Dargis, Michèle, Trépanier, Sonia, Hoshino, Shigeki, Koike, Tomohiro, Arai, Masaaki, Tsutsui, Naohisa
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.08.2021; Elsevier Limited
• Subjects: adjuvants; Agrobacterium radiobacter; Agrobacterium tumefaciens; Allergy and Immunology; Aluminum; Aluminum hydroxide; Animal model; Animal models; Antibodies; antibody formation; Antibody response; biomass; Chlorophyll; Chromatography; Cloning; Enzymes; Genes; genotype; Genotype & phenotype; Genotypes; Hepatitis B; Immune system; Immunogenicity; Infections; Influenza; Intestinal obstruction; Intussusception; live vaccines; Low income groups; Mortality; Nicotiana benthamiana; Plants; Plasmids; Proteins; Rabbits; risk; Rotavirus; Structural proteins; Toxicity; toxicology; Transmission electron microscopy; Ultrafiltration; Vaccine; Vaccines; Vectors (Biology); Virus-like particle; Virus-like particles; Viruses; Canada; Agrobacterium tumefaciens; Animal model; Virus-like particle; Nicotiana benthamiana; Vaccine; Rotavirus
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2021.07.039

•Rotavirus is the leading cause of diarrheal death in infants and young children.•Rotavirus-like particle (Ro-VLP) was produced in plant-agrobacterium vector system.•Ro-VLP of a human G1 strain composed of viral protein (VP) 7, VP6 and VP2.•G1 Ro-VLP elicited a robust homotypic immune response in rats.•G1 Ro-VLP did not show any significant toxicity in rabbits. Virus-like particles (VLPs) are unable to replicate in the recipient but stimulate the immune system through recognition of repetitive subunits. Parenterally delivered rotavirus-VLP (Ro-VLP) vaccine could have the potential to overcome the weaknesses of licensed oral live-attenuated rotavirus vaccines, namely, low efficacy in low-income and high mortality settings and a potential risk of intussusception. A monovalent Ro-VLP composed of viral protein (VP) 7, VP6 and VP2 of G1 genotype specificity was produced in Nicotiana benthamiana using Agrobacterium tumefaciens infiltration-based transient recombinant expression system. Plants expressing recombinant G1 Ro-VLP were harvested, then the resultant biomass was processed through a series of clarification and purification steps including standard extraction, filtration, ultrafiltration and chromatography. The purified G1 Ro-VLP was subsequently examined for its immunogenicity and toxicological profile using animal models. G1 Ro-VLP had a purity of ≥90% and was structurally similar to triple-layered rotavirus particles as determined by cryogenic transmission electron microscopy. Two doses of aluminum hydroxide-adjuvanted G1 Ro-VLP (1 μg, 5 μg or 30 μg), administered intramuscularly, elicited a robust homotypic neutralizing antibody response in rats. Also, rabbits administered G1 Ro-VLP (10 μg or 30 μg) four times intramuscularly with aluminum hydroxide adjuvant did not show any significant toxicity. Plant-derived Ro-VLP composed of VP7, VP6 and VP2 structural proteins would be a plausible alternative to live-attenuated oral rotavirus vaccines currently distributed worldwide.