Abstract

Vaccines for human use have conventionally been developed by the production of (1) microbial pathogens in eggs or mammalian cells that are then inactivated, or (2) by the production of pathogen proteins in mammalian and insect cells that are purified for vaccine formulation, as well as, more recently, (3) by using RNA or DNA fragments from pathogens. Another approach for recombinant antigen production in the last three decades has been the use of plants as biofactories. Only have few plant-produced vaccines been evaluated in clinical trials to fight against diseases, of which COVID-19 vaccines are the most recent to be FDA approved. In silico tools have accelerated vaccine design, which, combined with transitory antigen expression in plants, has led to the testing of promising prototypes in pre-clinical and clinical trials. Therefore, this review deals with a description of immunoinformatic tools and plant genetic engineering technologies used for antigen design (virus-like particles (VLP), subunit vaccines, VLP chimeras) and the main strategies for high antigen production levels. These key topics for plant-made vaccine development are discussed and perspectives are provided.

Highlights

  • Since the initial comprehension of vaccination by Jenner and Pasteur [1], vaccines for human use have been conventionally developed by the production of (1) microbial pathogens or (2) pathogen proteins in mammalian and insect cells, which are inactivated and/or purified for final formulations, and, very recently, (3) by using RNA or DNA [2]

  • The importance of new platforms for vaccine production is due to (1) the humanized virus problem, which minimizes the efficacy of egg-produced vaccines; (2) the use of eggs in case of influenza pandemics could be selfdefeating because they commonly originate in birds, so hens could be affected and produce less eggs, and (3), the virus could be lethal in chicken embryos and antigen production could be affected [5]

  • This review describes the elemental basis of antigen in silico design, plant transformation methods, recent virus-like particles (VLPs) developments, and the most advanced vaccines produced in plant cells, highlighting the main plants used as vaccine biofactories

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Summary

Introduction

Since the initial comprehension of vaccination by Jenner and Pasteur [1], vaccines for human use have been conventionally developed by the production of (1) microbial pathogens or (2) pathogen proteins in mammalian and insect cells, which are inactivated and/or purified for final formulations, and, very recently, (3) by using RNA or DNA [2] Another approach for antigen production is the use of plants as biofactories, which was initially proposed approximately three decades ago [3]). An attractive approach is the design and production of virus-like particles (VLPs) in plants as subunit vaccines This strategy has been useful to produce plant VLPs to fight against infectious diseases even at the industrial scale [8,14]. This review describes the elemental basis of antigen in silico design, plant transformation methods, recent VLP developments, and the most advanced vaccines produced in plant cells, highlighting the main plants used as vaccine biofactories

Genetic Antigen Design for Subunit Vaccine Development
Transformation Method and Yields
Findings
Transient Nuclear Transformation
Chloroplast Transformation
Main Plants Used as Biofactories in Vaccine Production
Plant Vaccines Today and Perspectives
Conclusions
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