Advances and challenges in the development and production of effective plant-based influenza vaccines

Abstract

Influenza infections continue to present a major threat to public health. Traditional modes of influenza vaccine manufacturing are failing to satisfy the global demand because of limited scalability and long production timelines. In contrast, subunit vaccines (SUVs) can be produced in heterologous expression systems in shorter times and at higher quantities. Plants are emerging as a promising platform for SUV production due to time efficiency, scalability, lack of harbored mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modifications. So far, several organizations have utilized plant-based transient expression systems to produce SUVs against influenza, including vaccines based on virus-like particles. Plant-produced influenza SUV candidates have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, the authors review ongoing efforts and challenges to producing influenza SUV candidates in plants and discuss the likelihood of bringing these products to the market.

Keywords:

• clinical development
• influenza
• plant expression system
• subunit vaccine
• transient expression
• virus-like particle

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Influenza infection presents a major public health issue. Due to frequent antigenic mutations and rapid spread of influenza viruses, influenza infections cause both annual epidemics and occasional pandemics.

• Currently licensed influenza vaccines are based on inactivated or live attenuated influenza viruses manufactured using embryonated hens’ eggs. Traditional manufacturing of influenza vaccines has limited scalability and long production times and does not satisfy global demand.

• SUVs are based on a pathogen’s antigen that can be produced in a heterologous expression system in a relatively short period of time and at high quantities and purities.

• Recombinant SUV production systems based on mammalian or insect cells have recently been developed as alternative to traditional egg-based influenza vaccine manufacturing; however, each system has limitations associated with cost, scalability and product safety.

• Plants are a promising SUV production platform due to their cost–effectiveness, scalability, lack of harbored mammalian pathogens and possession of eukaryotic protein post-translational modification machinery. Furthermore, a transient expression strategy allows for rapid production of SUVs in genetically unmodified plants under cGMP, with appropriate facilities already in place.

• Several influenza SUV candidates have been produced in plants and a few have advanced to clinical trials, demonstrating safety and immunogenicity in humans.

• Progression of plant-based influenza SUV candidates to the market will depend on demonstrating of their safety and efficacy in more advanced clinical trials, gaining the regulatory acceptance and their market competitiveness.

Notes