Plant-based Biomanufacturing for Vaccine and Drug Development

Plant-based biomanufacturing is emerging as a promising alternative in biopharmaceutical production, providing distinct advantages in biosafety, rapid scalability, and cost efficiency. Unlike mammalian cell systems, plant bioreactors eliminate the risk of human pathogen contamination and can be cultivated under simple, low-cost conditions using light, water, and basic nutrients. Compared to prokaryotic systems, plant bioreactors maintain essential post-translational modifications, with certain plant-derived glycosylation patterns even exhibiting intrinsic adjuvant properties. The development of highly efficient transient expression systems, particularly those mediated by Agrobacterium tumefaciens, has further accelerated the use of plant-based production. These systems enable recombinant protein expression within days instead of months, making them especially suitable for rapid response to emerging infectious diseases or other public health emergencies. Plant hosts provide significant flexibility, encompassing a wide range of species from model organisms, such as tobacco and Arabidopsis to crops, such as rice and maize. Furthermore, diverse cultivation formats are available, including whole plants, hairy roots, callus cultures, and suspension cell systems. This dual diversity in both species and cultivation approaches provides customizable solutions tailored to different product types and production scales. Several commercial and clinical-stage products reveal the practical viability of plant molecular farming. Notable examples include the tobacco-derived virus-like particle (VLP) coronavirus of 2019 (COVID-19) vaccine, a carrot cell-based recombinant enzyme for the treatment of Gaucher disease, and rice endosperm-produced recombinant human serum albumin. These cases show the applicability of plant systems across multiple therapeutic categories, from prophylactic vaccines to replacement enzymes and plasma protein substitutes. Despite these advances, several technical and regulatory difficulties persist. Protein expression levels in plants are often limited by large cell sizes and low cell densities per culture volume. Correct folding and assembly of complex proteins remain challenging, and downstream purification is complicated by the release of host cell proteins and secondary metabolites during extraction, a process that can account for up to 90% of total production costs. Immunogenic plant-specific glycans may require glycoengineering to minimize undesired immune responses. Moreover, achieving batch-to-batch consistency and addressing environmental biosafety concerns, such as pollen pollution in field-grown crops, are critical for industrial scale-up. Finally, the absence of globally harmonized regulatory pathways further complicates market entry and commercial adoption. Looking ahead, the advancement of plant-based bioproduction should focus on multiple interrelated objectives. Expression yields could be improved through refined vector design, optimized expression cassettes, and strategic co-expression of molecular chaperones. Downstream processing may be simplified by adopting secretion-based strategies, self-aggregating fusion tags, and more efficient purification workflows. The development of genetically uniform and highly dispersible suspension cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)-mediated editing will further support scalable manufacturing. Concurrently, establishing plant-specific good manufacturing practice guidelines is essential to ensure consistent product quality and safety. By integrating innovations in synthetic biology, process engineering, and regulatory frameworks, plant-based systems are positioned to mature into a reliable and adaptable production platform, thereby contributing to a more resilient and diversified supply chain for biologics, vaccines, and high-value plant metabolites.