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Analytical technologies for influenza virus-like particle candidate vaccines: challenges and emerging approaches

Christine M Thompson12, Emma Petiot1, Alexandre Lennaertz12, Olivier Henry2 and Amine A Kamen12*

Author Affiliations

1 National Research Council Canada, Vaccine Program – Human Health therapeutics Portfolio, 6100 Royalmount Avenue, Montreal, Québec H4P 2R2, Canada

2 École Polytechnique de Montréal, C.P. 6079, succ. Centre-ville, Montréal, Québec H3C 3A7, Canada

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Virology Journal 2013, 10:141  doi:10.1186/1743-422X-10-141

Published: 4 May 2013


Influenza virus-like particle vaccines are one of the most promising ways to respond to the threat of future influenza pandemics. VLPs are composed of viral antigens but lack nucleic acids making them non-infectious which limit the risk of recombination with wild-type strains. By taking advantage of the advancements in cell culture technologies, the process from strain identification to manufacturing has the potential to be completed rapidly and easily at large scales. After closely reviewing the current research done on influenza VLPs, it is evident that the development of quantification methods has been consistently overlooked. VLP quantification at all stages of the production process has been left to rely on current influenza quantification methods (i.e. Hemagglutination assay (HA), Single Radial Immunodiffusion assay (SRID), NA enzymatic activity assays, Western blot, Electron Microscopy). These are analytical methods developed decades ago for influenza virions and final bulk influenza vaccines. Although these methods are time-consuming and cumbersome they have been sufficient for the characterization of final purified material. Nevertheless, these analytical methods are impractical for in-line process monitoring because VLP concentration in crude samples generally falls out of the range of detection for these methods. This consequently impedes the development of robust influenza-VLP production and purification processes. Thus, development of functional process analytical techniques, applicable at every stage during production, that are compatible with different production platforms is in great need to assess, optimize and exploit the full potential of novel manufacturing platforms.

Influenza virus-like particles (VLPs); Quantification; Process Analytical Technologies; Total particles; Vaccines