Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

Abstract

The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient’s plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far.

Soluble Human Angiotensin- Converting Enzyme 2 as a Potential Therapeutic Tool for COVID-19 is Produced at High Levels In Nicotiana benthamiana Plant With Potent Anti-SARS-CoV-2 Activity

“…1998; Gleba et al, 2005;Tusé, 2011;Tusé et al, 2014Tusé et al, , 2020Walwyn et al, 2015;Nandi et al, 2016;Alam et al, 2018;McNulty et al, 2020;Shanmugaraj et al, 2020;Maharjan and Choe, 2021). Plant expression systems have several advantages over other expression systems currently in use, such as rapid and high production with the ability to accumulate grams of target protein per kilogram of biomass in less than a week (Gleba et al, 2005;Sainsbury et al, 2009;Holtz et al, 2015;Maharjan and Choe, 2021).…”

“…Therefore, the aim of this study is to lead to the production of an affordable, safe, and functional active recombinant human ACE2 using the plant transient expression system for use in the treatment of COVID-19. A plant expression system is a promising expression platform for a cost-effective, fast, and safe production of a variety of recombinant proteins, vaccines, antibodies, therapeutic proteins, and enzymes ( Conrad et al, 1998 ; Gleba et al, 2005 ; Tusé, 2011 ; Tusé et al, 2014 , 2020 ; Walwyn et al, 2015 ; Nandi et al, 2016 ; Alam et al, 2018 ; McNulty et al, 2020 ; Shanmugaraj et al, 2020 ; Maharjan and Choe, 2021 ). Plant expression systems have several advantages over other expression systems currently in use, such as rapid and high production with the ability to accumulate grams of target protein per kilogram of biomass in less than a week ( Gleba et al, 2005 ; Sainsbury et al, 2009 ; Holtz et al, 2015 ; Maharjan and Choe, 2021 ).…”

“…A plant expression system is a promising expression platform for a cost-effective, fast, and safe production of a variety of recombinant proteins, vaccines, antibodies, therapeutic proteins, and enzymes ( Conrad et al, 1998 ; Gleba et al, 2005 ; Tusé, 2011 ; Tusé et al, 2014 , 2020 ; Walwyn et al, 2015 ; Nandi et al, 2016 ; Alam et al, 2018 ; McNulty et al, 2020 ; Shanmugaraj et al, 2020 ; Maharjan and Choe, 2021 ). Plant expression systems have several advantages over other expression systems currently in use, such as rapid and high production with the ability to accumulate grams of target protein per kilogram of biomass in less than a week ( Gleba et al, 2005 ; Sainsbury et al, 2009 ; Holtz et al, 2015 ; Maharjan and Choe, 2021 ). This system has been successfully used for the production of functional active complex proteins, such as full length Pfs48/45 of Plasmodium falciparum ( Mamedov et al, 2019b ), human Furin, Factor IX ( Mamedov et al, 2019a ), glycohormone erythropoietin ( Grosse-Holz et al, 2018 ), latent transforming growth factor-beta (TGF-beta) ( Wilbers et al, 2016 ), human epidermal growth factor ( Hanittinan et al, 2020 ), PA83 of B. anthracis ( Mamedov et al, 2016 , 2017 ), HIV gp140, other viral glycoproteins ( Margolin et al, 2018 , 2020a ), and antigens against influenza, Ebola, dengue, rotavirus, and norovirus ( Mett et al, 2008 ; Landry et al, 2014 ; Rybicki, 2014 ; Pêra et al, 2015 ; Takeyama et al, 2015 ).…”

Plant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies

“…Nonetheless, researchers are working hard on plant-based COVID-19 vaccine development via glycoengineering technology and plant-based vaccines have low cost production, rapidity, scalability, and safety [202] . The pharmacological properties and stability, solubility, bioavailability, pharmacokinetics, and immunogenicity of glycosylated biotherapeutics can be determined by the glyco-biotechnological approach, which can propel scientific research to the development of the next generation of biotherapeutics and glycoengineered vaccines [203] .…”

Attacking the Intruder at the Gate: Prospects of Mucosal Anti SARS-CoV-2 Vaccines

“…The production of vaccine antigens derived from plants can become cost-effective system for the large-scale production of human therapeutic proteins [60,69]. The use of plants to produce vaccine antigens ensures that all post-translational modifications are completed in the protein of interest since plants possess the expression, folding, assembly and glycosylation machinery required to achieve the antigen's structure and biological activity.…”