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.

Highlights

  • Since the first report on the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing coronavirus disease 2019 (COVID-19) in China at the end of 2019, it has spread across 220 countries and territories, infected 160 million people, and caused the deaths of 3.3 million people as of June 19, 2021 [1]

  • The immunogenicity results demonstrated that adjuvant formulations have a greater potential to improve humoral and cellular immune responses to the coronavirus virus-like particle (CoVLP) vaccine compared with non-adjuvant formulations

  • No dose-dependent effect was observed for CoVLP formulated with CpG 1018, which might be the reason for its exclusion from the phase 2/3 clinical trial

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Summary

Introduction

Since the first report on the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing coronavirus disease 2019 (COVID-19) in China at the end of 2019, it has spread across 220 countries and territories, infected 160 million people, and caused the deaths of 3.3 million people as of June 19, 2021 [1]. The transient expression system can produce a target antigen within one week after introducing an antigen-coding sequence into plants, compared to one or several years via the transgenic expression system [18] This unique feature of the transient expression system for rapid vaccine production tends to be the first and an excellent choice to produce a vaccine, especially in an emergency such as the COVID-19 pandemic. The plant-based recombinant protein production approach has been implemented for the development of vaccines, diagnostic reagents, and therapeutics for COVID-19 and has progressed into clinical trials [48,49,50,51,52,53,54,55,56,57].

Plant-Based Vaccine Production for Epidemic Response
Clinical Trial Results for CoVLP
COVID-19 Vaccines in the Preclinical Stage
Second-Generation COVID-19 Vaccines in the Preclinical Stage
Conclusions and Future Perspectives
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