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.