JOSÉ CASTILLO
CEO, Quantoom Biosciences (a Univercells company), Nivelles, Belgium

Abstract

mRNA vaccine is the newest type of vaccine available to the public and has great prospects in terms of speed from research to market. In manufacturing, some barriers observed during Covid can already be lifted up such as (A) a slow transition from research to commercialisation, (B) unequal access to vaccines across countries and (C) inadequate supply of raw materials. Solutions have already been found for (A) a quicker shift from benchwork to commercialisation with a manufacturing process based on repeat-batch production of in vitro transcription (IVT), (B) technology that is small, straightforward to use, modular and transportable to diverse locations and (C) increased number of suppliers for critical raw materials, which are reputable for reliable and predictable deliveries. RNA production with Ntensify™ starts with DNA templates which are first transcribed into RNAs and then purified, ready for encapsulation. In this process, the reaction volume of the in vitro transcription (IVT) is fixed to 20 mL. Large-scale manufacturing occurs by 20 mL increment: i.e. repeat-batch production, with the benefit of an already optimal ratio for reagents (a process co-developed with our partner eTheRNA), which avoids dedicating time to optimisation when entering production. With both high yields and low impurities RNAs, purification can be simplified to a single step. To demonstrate that our approach in 20 mL is successful, several constructs were tested using this process. Their sequence length ranges from 1999 and 4060 ribonucleotides. mRNA reaction yield is on average 5.1 mg/mL. Analysis of the data shows that all batches met the specification limits, where defined.

OPINION ARTICLE
mRNA vaccines played a pivotal role in helping to bring the Covid-19 pandemic under control. Usually the development of vaccines takes several years, and sometimes even decades. But in as little as a year, several vaccines were developed against Covid including two mRNA vaccines (1-2). This unprecedented achievement highlights the great potential of this new class of medication. However, like other new products on the market, mRNA vaccines face multiple barriers in their development and production. While mRNA therapeutics are relatively quick to make they are difficult to scale up to commercial manufacture. Scale-up requires substantial optimisation which is very time-consuming.

QUICK RECAP: HOW MRNA MEDICINES ARE DEVELOPED

Taking the Covid vaccine as an example
The first step in vaccine development is aimed at identifying strategic antigens of the Covid virus which could be of interest to protect against infection. The membrane-bound spike protein is often neutralised by antibodies in convalescent patients. These anti-spike antibodies were shown to not ...