Advances in influenza virus-like particles bioprocesses

ABSTRACT

Introduction: Influenza Virus-like Particles (VLPs) are one of the most promising vaccine strategies to complement traditional egg-based processes and contribute to shortening the response time when facing future pandemics. Research programs have taken advantage of the potential of this approach to produce influenza VLPs on a variety of cellular platforms, reaching the industrial level of development and recent commercialization.

Area covered: This review aims to give an overview of available strategies for influenza-VLP production and their respective stages of development, from small-scale preclinical studies to large-scale industrial processes. Recent trends and fulfillments in purification schemes of influenza VLP were also reviewed with regards to quality and potency requirements that go along with influenza vaccine manufacturing.

Expert opinion: In the next five years, it is expected that there will be licensing of new influenza vaccine products based on VLP strategy. Few VLP upstream processes are mature enough and close to fully complement or seriously concurrence the ovoculture process. Nevertheless, many improvements have yet to be achieved in downstream processes. In the next few years, research efforts in this field are expected to provide purification strategies and tools to achieve higher recovery yields and improve the cost-effectiveness of VLP processes.

KEYWORDS:

• Influenza Virus-like Particles
• Recombinant vaccine
• Upstream Process (USP)
• Downstream Process (DSP)

Declaration of interest

L. Durous acknowledges the Auvergne Rhône-Alpes Region for his PhD grant (ARC 1 Santé). 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

A reviewer has disclosed that they are both a Professor at McGill University and also that they serve as the Medical Officers for Medicago Inc., a late-phase pre-commercial company that produces VLP influenza vaccines in plants.

Article highlights

• Description of cellular platforms and techniques used for influenza-VLP production, from small-scale preclinical studies to large-scale industrial processes.

• Comparative analysis of influenza protein expression strategies based on evaluation of 70 published studies, highlighting the widespread utilization of Baculovirus-Insect cell system in both academic and industrial studies.

• Overview of purification schemes showing the implementation of scalable membrane- and chromatography-based processes.

• Limitation of large-scale process development due to the availability of specific quantification methods for influenza VLPs.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by European Comission - FP7-PEOPLE-2013-IIF - Marie Curie Action: "International Incoming Fellowships" Program - Project FLU-MAL VLP grant agreement ID: 624939.