The Promise of mRNA Vaccines

February 10, 2020

Translate Bio’s Chief Technology Officer, Frank DeRosa, co-authored a review published in npj Vaccines:  The promise of mRNA vaccines: a biotech and industrial perspective. Here, Dr. DeRosa answers questions on this topic in the context of Translate’s partnership with Sanofi Pasteur to develop mRNA vaccines for infectious diseases. In March, 2020, both companies announced a collaboration to develop a novel mRNA vaccine for SARS-CoV-2, the novel coronavirus responsible for the disease known as COVID-19.

Q. How does an mRNA vaccine work?

A. Vaccines work by mimicking disease agents (immunogens) to stimulate the immune system, thereby building up a defense mechanism (antibodies) that can be deployed to fight future infections. mRNA vaccines offer an innovative approach towards the prevention of disease. By delivering mRNA that codes for the pathogen of interest, mRNA vaccines enable the body to produce the desired immunogen within the cell. The newly expressed immunogen can be processed to trigger innate and adaptive immune responses towards the target antigen. This potentially leads to a potent and rapid response resulting in antigen-specific immunity to prevent future disease. The exciting thing about this technology is that it could support the development of vaccines for disease areas where vaccination is not a viable option today.

“mRNA-based vaccines hold the promise to revolutionize the field by addressing current manufacturing challenges and offering novel vaccine compositions.”

— Jackson et al, npj Vaccines

Q. What are the advantages of using an mRNA-based vaccine compared with the conventional vaccine approach?

A. There are multiple advantages to utilizing an mRNA-based vaccine over traditional approaches such as recombinant-based proteins.  There can be inherent difficulties in the production and purification of many target immunogens which can prove detrimental for a recombinant protein approach.  For example, some vaccine immunogens can involve specific post-translational modifications and conformations which may be difficult to reproduce from a recombinant-based production.  This can be further complicated when multi-antigen complexes are required for a proper immune response.  Further, some immunogens are highly hydrophobic in nature and are extremely difficult to produce, isolate and purify in their proper conformational state.  An mRNA-based vaccine can potentially overcome these challenges through the body’s own production of the antigen(s), which can undergo the proper post-translational folding, modifications and presentation to elicit a proper immune response.  This opens the door to enable the prevention of diseases that were previously deemed “undruggable” through such traditional means. Another important advantage of an mRNA-based approach is in how mRNA can be manufactured. A highly scalable, cell-free process allows for the production of a substantial number of different target mRNA constructs with a relatively small manufacturing footprint.  The flexibility of using production and purification manufacturing processes that are easily adaptable across multiple targets by simply changing one component of the process, the linearized plasmid DNA template, allows for an extraordinarily rapid and cost-effective way to achieve successful production of mRNA construct vaccine candidates.

Q. What are the key takeaways from the Review Article?

A. The advantages and applications of multiple types of mRNA (non-replicating (NRM) and self-amplifying (SAM)) for vaccines are evident and promising.  These include many aspects of the development of mRNA vaccines from the discovery of immunogens to rapid response manufacturing. In the Review Article, we wanted to provide a viewpoint from an industrial perspective that addressed the accomplishments achieved throughout the field to date, while discussing the challenges in front of all of us working in this field. Building upon the extensive preclinical data generated, clinical trials in recent years have informed our understanding of the key properties needed to establish an acceptable risk/benefit profile for a given vaccine but there is still work to be done in this area.  While there are still challenges ahead both in research and clinical trial outcomes, we remain extremely optimistic about the ways that mRNA-based vaccines may revolutionize the field, with potentially huge impact from both a medical and manufacturing perspective.

Q. How is the Sanofi Pasteur collaboration going?

A. Our Sanofi Pasteur partnership continues to be a highly productive  and collaborative effort.  The teams work extremely well together and have generated substantial data sets across multiple disease targets.  We are excited with the data generated thus far, the pace of development, the teamwork and the shared focus on the ultimate goal of producing clinical candidates for a number of infectious diseases.  This is a synergistic partnership and an important extension of the platform that we have built here at Translate Bio. In March 2020, we announced plans to jointly develop a novel mRNA vaccine for COVID-19, leveraging our existing partnership agreement.

To access the full review article, visit npj Vaccines here.