Plant-made vaccines against viral diseases in humans and farm animals

Abstract

Plants provide not only food and feed, but also herbal medicines and various raw materials for industry. Moreover, plants can be green factories producing high value bioproducts such as biopharmaceuticals and vaccines. Advantages of plant-based production platforms include easy scale-up, cost effectiveness, and high safety as plants are not hosts for human and animal pathogens. Plant cells perform many post-translational modifications that are present in humans and animals and can be essential for biological activity of produced recombinant proteins. Stimulated by progress in plant transformation technologies, substantial efforts have been made in both the public and the private sectors to develop plant-based vaccine production platforms. Recent promising examples include plant-made vaccines against COVID-19 and Ebola. The COVIFENZ® COVID-19 vaccine produced in Nicotiana benthamiana has been approved in Canada, and several plant-made influenza vaccines have undergone clinical trials. In this review, we discuss the status of vaccine production in plants and the state of the art in downstream processing according to good manufacturing practice (GMP). We discuss different production approaches, including stable transgenic plants and transient expression technologies, and review selected applications in the area of human and veterinary vaccines. We also highlight specific challenges associated with viral vaccine production for different target organisms, including lower vertebrates (e.g., farmed fish), and discuss future perspectives for the field.

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans

“…The plant-made COVID-19 vaccine development efforts were recently well-reviewed by Su et al ( 20 ). Many such parenteral candidate vaccines are in their early stages of application, with few commercialized for research and diagnostic purposes ( 20 ).…”

“…The plant-made COVID-19 vaccine development efforts were recently well-reviewed by Su et al ( 20 ). Many such parenteral candidate vaccines are in their early stages of application, with few commercialized for research and diagnostic purposes ( 20 ). In this study, we report the first edible COVID-19 tomato vaccine, TOMAVAC, derived by constitutively overexpressing the consensus sequence of the S1 protein of SARS-CoV-2, covering the sequence variation of SARS-CoV-2 spread in Uzbekistan ( 26 ).…”

“…There is an opportunity to develop lyophilized ( 8 , 14 ) TOMAVAC-based capsules ( 5 ) with standardized edible doses for safe delivery and enhanced immunogenicity ( 14 ), which demand future investigations with the availability of higher-generation stable transgenic tomato plants. These will help to produce sufficient standardized TOMAVAC for conducting large-scale human consumption clinical trials justifying (a) the efficiency of protection against current and emerging COVID-19 infections and (b) public perception and acceptance ( 12 , 14 ), as well as proper regulatory measures ( 20 ), which require future investigations and investments.…”

“…They also offer an opportunity for targeted folding and post-translational modifications of antigenic proteins with the desired properties ( 5 , 15 ). Several attempts have been made toward developing plant-based COVID-19 vaccines ( 5 , 16 – 20 ), and many plant-carrier-based examples exist for various infectious diseases ( 8 , 9 , 12 – 14 ). Here, we present the results of our efforts in developing transgenic tomato plants expressing the RBD subunit of the S1 protein of SARS-CoV-2 with early evidence for the immunogenicity, neutralizing activity, and safety of the first tomato-based edible vaccine (TOMAVAC) against COVID-19.…”

Challenges and Opportunities in the Process Development of Chimeric Vaccines

“…Several host plants that have been used as potential expression platforms are tobacco ( Nicotiana benthamiana , Nicotiana tabacum ), Arabidopsis thaliana , rice ( Oryza sativa ), maize ( Zea mays ), potato ( Solanum tuberosum ), tomato ( Lycopersicon esculentum ), and lettuce ( Lactuca sativa ) [ 136 ]. Recently, the tobacco expression platform was used to develop a commercially available Covifenz ® (Medicago Inc., Quebec, Canada and GlaxoSmithKline, Brentford, UK) vaccine against COVID-19 [ 137 ]. Dobrica et al [ 138 ] demonstrated the production of a novel, cost-effective chimeric antigen against the hepatitis B virus in Nicotiana benthamiana.…”