Messenger RNA-based vaccine production has become a major industry focus, thanks to the success of jabs developed during the pandemic. However, under normal circumstances, DNA-based manufacturing may be the better option.
Researchers at the Aristotle University of Thessaloniki (AUTH) in Greece reached this conclusion after comparing the “technoeconomics” of DNA-based vaccine production with mRNA-based methods used to make shots like Spikevax and Comirnaty.
Co-author Andreas Ouranidis, research coordinator and teaching assistant
at the AUTH School of Medicine, told GEN, “Our analysis attempted to identify the limitations and production challenges of each manufacturing approach, quantifying the underlying hurdles and risks associated.”
Digital shadows
The team used “digital shadows,” in silico data representations, to compare DNA-based monoclonal antibody and antigen manufacturing with in vitro transcribed (IVT) mRNA vaccine production processes.
The shadows included cost estimates for each unit operation as well as the raw materials and reagents required. The researchers also generated an estimation of the minimum selling price per dose (MSPD) for each type of vaccine.
And the key finding was that—in the absence of a global health emergency—DNA-based vaccine production has the more attractive commercial profile.
“Our findings reveal that, under steady demand market conditions allowing for planned production campaigns, recombinant DNA-based vaccine manufacturing offers higher potential profitability,” Ouranidis said.
In short, for an equal number of doses, DNA manufacturing is likely to be more profitable than IVT mRNA production because the latter approach has high raw material requirements associated with the linearization and in vitro transcription steps.
The authors also cited the “proven, well-grounded protocols for both upstream and downstream process development” that are available for DNA-based vaccine production as advantages.
Ouranidis said the findings should inform industry and health authorities, commenting, “The two vaccine manufacturing methods represent significant benefits and trade-offs that must be considered when addressing global needs.”
Production bottlenecks
Despite being positive about DNA-based vaccine production in general, the study did identify areas in need of better manufacturing technologies.
Ouranidis said, “At present, recombinant DNA technology is constrained by upstream process challenges that could benefit from automation.”
He added, “Artificial Intelligence (AI) will improve process control and therefore product quality thus reducing failures and increasing efficiency of operations.”
