Challenges in the development of egg-independent vaccines for influenza

ABSTRACT

Introduction: Current influenza vaccines are mainly produced from viruses propagated in eggs, an established process developed over 70 years. However, this technology presents some drawbacks and other platforms are under development or have been already developed in order to replace or to be used alongside the old one.

Area covered: The present review provides an overview of influenza vaccine production, starting from egg-based technology, to cell-derived vaccines, until the novel platforms/technologies for the production of influenza vaccines such as DNA-based vaccines, virus-like particles and plant-based technology.

Expert opinion: The ideal method of production should have certain characteristics such as great flexibility and scalability, the viruses should be representative of the circulating strains, process should be standardized and controlled, and it should be possible to start production as soon as the sequence of the new influenza strain is available. However, it is important not to underestimate the fact that some parts of the vaccine production process have been established for egg-based vaccines. Thus, changes in vaccine production methods are not merely ‘technical changes’; rather, they involve various aspects that slow down the authorization of new influenza vaccines and make the complete replacement of egg-based production unlikely in the near future.

KEYWORDS:

• Cell culture platform
• DNA-based vaccine
• egg-based technology
• influenza vaccines
• plant-based technology
• virus like particles

Article Highlights

• The influenza vaccine virus selection and development is a result of a complex process and intense collaborations among the World Health Organization, vaccine manufacturers, regulatory agencies and global public health laboratories.

• Most of the current influenza vaccines are still produced and/or isolated in eggs, an established process that presents some drawbacks and critical issues such as adaptations acquired by influenza viruses, dependence on the availability of eggs and long time-frame.

• The cell-culture platform has many advantages over egg production and three cell lines have been extensively studied and applied to influenza vaccine production: MDCK, Vero and PERC.C6.

• In recent decades, several novel platforms and technologies have been developed in order to overcome the drawbacks of egg-based vaccine production and eventually to replace this old-fashioned method. Some of the platforms/technologies that seem to be very promising are: DNA-based vaccines, virus-like-particles and plant-based approach.

• Regulatory changes could be necessary and some parts of the production process have been established for egg-based vaccines and may not be optimal for other types of vaccines; thus, a general revision of the process is required.

• The ideal method of production should have certain characteristics: great flexibility and scalability; the viruses should be representative of the circulating strains; production should be cheap and safe, and yield large quantities at the same time. Process should be standardized and controlled, and it should be possible to start production as soon as the sequence of the new influenza strain is available.

• A perfect platform does not exist and the choice should be made by balancing advantages and disadvantages from different points of view.

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.