Developing a production process for influenza VLPs: a comparison between HEK 293SF and Sf9 production platforms

Christine M Thompson,Emma Petiot,Amine A Kamen,Olivier Henry,Marc G Aucoin

doi:10.1186/1753-6561-7-s6-p22

Christine M Thompson, Emma Petiot + Show 3 more

Open Access

https://doi.org/10.1186/1753-6561-7-s6-p22

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Abstract

Background Influenza virus-like particle (VLP) vaccines are one of the most promising approaches to respond to the constant threat of the emergence of pandemic strains, as they possess the potential for higher production capabilities compared to traditional vaccines made in egg-based technology. VLPs are particles produced in cell culture utilizing recombinant protein technology composed of viral antigens that are able to elicit an immune response but lack viral genetic material. Thus far, influenza VLPs have been produced in mammalian, insect and plant based platforms [1], with production in insect cells being the most explored. Baculovirus with mammalian promoters (Bacmam) have been shown to efficiently transduce mammalian cells and further express genes but are unable to replicate, efficiently repressing baculovirus (BV) production that leads to contamination downstream [2]. Influenza VLP production was performed in HEK 293SF cells using the Bacmam gene delivery system. The proposed system was assessed for its ability to produce influenza VLPs composed of Hemagglutinin (HA), Neuraminidase (NA) and Matrix Protein (M1) and compared to VLPs produced in Sf9 cells through the lens of bioprocessing.

Highlights

Influenza virus-like particle (VLP) vaccines are one of the most promising approaches to respond to the constant threat of the emergence of pandemic strains, as they possess the potential for higher production capabilities compared to traditional vaccines made in egg-based technology
It was found that VLPs were associated with the cell pellet after harvest in relatively the same amount as released into the supernatant in the form of unreleased VLPs from Negative Staining Electron Microscopy (NSEM) and HA assay analysis
Sf9 cells produced more uniformly shaped VLPs that were spherical in shape, around 100 nm in size and were found to be mainly in the supernatant, not associated with the cell pellet

Summary

Introduction

Influenza virus-like particle (VLP) vaccines are one of the most promising approaches to respond to the constant threat of the emergence of pandemic strains, as they possess the potential for higher production capabilities compared to traditional vaccines made in egg-based technology. * Correspondence: amine.kamen@cnrc-nrc.gc.ca 1Human Health Therapeutics, Vaccine Program, NRC, Montréal, Québec, H4P 2R2, Canada Full list of author information is available at the end of the article Results It was found that VLPs from the HEK 293SF system were present in the culture supernatant in a heterogeneous mixture in terms of particle shape and size.

Results

Conclusion