Efficient upscaling of mCuMVTT-VLPs vaccine
candidate
Manufacturability, in particular scalability and production yield, is a
critical attribute in selecting vaccines candidates to address a global
pandemic. For this reason, we focused from the beginning on a VLP-based
vaccine that can be efficiently produced in bacteria. Indeed, as the RBM
of SARS-CoV-2 is not glycosylated and has no other posttranslational
modifications, it may be an optimal candidate for a VLP-based vaccine
candidate produced in E. coli .
Continuous flow ultracentrifugation is a method used to produce
>80% of the annual global influenza vaccine inventory
which is approximately 1.5 billion doses (33), Continuous flow
ultracentrifugation is thus an ideal and an established method for
purification at large scale. To assess the potential yields of our
production process, we produced a batch of mCuMVTT-RBM
in a 2litre fermenter and purified the resultant VLPs by continuous flow
ultracentrifugation (Fig 7A). SDS PAGE analysis showed good
incorporation of RBM and EM-analysis showed well-formed particles (Fig.
7B-D). The process yield from 2L of fermentation volume was
approximately 0.5 g. This would correspond to 2.5 mio doses produced in
a single 1000-liter fermentation run. As this process is not optimized,
there is the potential to significantly improve the already impressive
yield.