Abstract
The recent COVID-19 pandemic has highlighted the value of technologies that allow a fast setup and production of biopharmaceuticals in emergency situations. The plant factory system can provide a fast response to epidemics/pandemics. Thanks to their scalability and genome plasticity, plants represent advantageous platforms to produce vaccines. Plant systems imply less complicated production processes and quality controls with respect to mammalian and bacterial cells. The expression of vaccines in plants is based on transient or stable transformation systems and the recent progresses in genome editing techniques, based on the CRISPR/Cas method, allow the manipulation of DNA in an efficient, fast, and easy way by introducing specific modifications in specific sites of a genome. Nonetheless, CRISPR/Cas is far away from being fully exploited for vaccine expression in plants. In this review, an overview of the potential conjugation of the renewed vaccine technologies (i.e., virus-like particles—VLPs, and industrialization of the production process) with genome editing to produce vaccines in plants is reported, illustrating the potential advantages in the standardization of the plant platforms, with the overtaking of constancy of large-scale production challenges, facilitating regulatory requirements and expediting the release and commercialization of the vaccine products of genome edited plants.
Highlights
The advances in molecular biology techniques, together with the reverse vaccinology applications, have led to the development of recombinant subunit vaccines, which, unlike attenuated pathogens, are based on antigenic epitopes or sugar/protein/protein complexes [1,2].For decades, recombinant protein vaccines have been produced at industrial scale in systems based on bacterial, insect, mammalian, and yeast cells that, useful, require high costs and efficient equipment for large-scale fermentation and purification
Plant-based human vaccines and monoclonals are not approved for the market yet, several vaccine candidates against bacteria, fungi, or viruses have been successfully produced in various plant systems and tested in preclinical models, for immunogenicity and safety, or under clinical trials, for safety and efficacy [4,5,6]
This review provides an overview of the most renewed techniques of vaccine development in plants and the synergism resulting from the conjugation of these technologies with genome editing methods based on CRISPR/Cas
Summary
The advances in molecular biology techniques, together with the reverse vaccinology applications, have led to the development of recombinant subunit vaccines, which, unlike attenuated pathogens, are based on antigenic epitopes or sugar/protein/protein complexes [1,2]. In 2001, the US Defense Advanced Research Projects Agency sponsored the Blue Angel Project aimed at addressing the insufficient capability of providing vaccines against pandemics caused by new pathogens/strains and intentional biothreats Within this project, a high containment, self-sufficient plant-based pharmaceutical production facility, able to manufacture 10 million doses of an H1N1 influenza vaccine in a single month, was created [7]. The recent progresses in genome modification have brought the development of the targeted genome editing based on the CRISPR (Cluster Regularly Interspersed Short Palindromic Repeats)-Cas technique that allows an efficient and fast introduction of specific targeted mutations/deletions/insertions in specific sites of a genome [12,13] This method has been successfully applied to plant genetic engineering, expediting the release of genome edited plants [14]. The potential innovations in the standardization of the plant platforms are illustrated together with the overtaking of constancy of large-scale production challenges, expediting the release and commercialization of the vaccine products from genome edited plants
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