Plant-Based Virus-like Particle (VLP) Vaccines Against Influenza and Hepatitis Viruses

The rapid evolution of pathogens, particularly viruses, poses a continuous threat to global public health, necessitating the development of highly scalable and cost-effective vaccine platforms. Plant-based virus-like particles (VLPs) have emerged as a transformative approach in vaccinology, leveraging the innate capacity of plant systems to produce highly immunogenic, non-infectious, and structurally authentic viral mimics. VLP-based recombinant antigens contained within the plant tissues (particularly in seeds) show better stability and can be transported and stored at ambient temperatures, without the requirement of a cold chain framework, and edible vaccines offer needle-free vaccine administration. Plant-based expression systems use natural cellular structures such as plant cell walls and seed endosperms to encase antigens, functioning as a natural shield against digestion and thermal degradation. Grain host plants are inimitably adapted for prolonged storage owing to natural seed desiccation wherein recombinant antigens accumulate within vacuoles or intracellular protein bodies segregated from active degradation. By simply cultivating more plants, vaccine production can be scaled up while transient plant expression systems speed up production within a few weeks, which is critical for quick responses to emerging new disease outbreaks. By genetic modification, plants can be used to express several antigens, facilitating the development of multi-component vaccines against many diseases at a single shot. Recently, plant-derived VLP vaccines, principally targeting influenza and hepatitis viruses, have been shown to elicit robust immune responses through the expression of their surface antigens in plants such as lettuce, potato, and tobacco (Nicotiana benthamiana). Despite their potential, significant challenges persist, including the achievement of consistent dosing, the attainment of high and reproducible expression levels, and the navigation of complex regulatory frameworks for plant-derived pharmaceuticals which remain unsolved. The current review focuses on recent developments in the production of plant-based influenza and hepatitis vaccines and explores the advantages, challenges, and application of such vaccines in combating these infections.