Background: Influenza is a widely distributed infection that almost annually causes seasonal epidemics.
The current egg-based platforms for influenza vaccine production are facing a number of challenges and are
failing to satisfy the global demand in the case of pandemics due to the long production time. Recombinant vaccines
are an alternative that can be quickly produced in high quantities in standard expression systems.
Methods: Plants may become a promising biofactory for the large-scale production of recombinant proteins due
to low cost, scalability, and safety. Plant-based expression systems have been used to produce recombinant vaccines
against influenza based on two targets; the major surface antigen hemagglutinin and the transmembrane
Results: Different forms of recombinant hemagglutinin were successfully expressed in plants, and some plantproduced
vaccines based on hemagglutinin were successfully tested in clinical trials. However, these vaccines
remain strain specific, while the highly conserved extracellular domain of the M2 protein (M2e) could be used for
the development of a universal influenza vaccine. In this review, the state of the art in developing plant-produced
influenza vaccines based on M2e is presented and placed in perspective. A number of strategies to produce M2e
in an immunogenic form in plants have been reported, including its presentation on the surface of plant viruses or
virus-like particles formed by capsid proteins, linkage to bacterial flagellin, and targeting to protein bodies.
Conclusion: Some M2e-based vaccine candidates were produced at high levels (up to 1 mg/g of fresh plant tissue)
and were shown to be capable of stimulating broad-range protective immunity.