The Pfizer/BioNTech and the Moderna COVID-19 vaccines were the first mRNA (messenger ribonucleic acid) vaccines in the world to complete all clinical trial stages and be approved for use. As a result of the attention garnered via the launch of these high-profile mRNA vaccines alongside several decades of research, a new branch of medicine has emerged, one focused on looking at how mRNA vaccines could prevent outbreaks of other infectious diseases.
Already, this field of research is evolving, and scientists now theorize that mRNA could be leveraged to treat and prevent chronic diseases, such as cancer.
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mRNA vaccines open up new possibilities
The first use of vaccinations dates back to the 18th century when contagious diseases such as smallpox were rampant. Over the years, vaccine development has evolved alongside the growth of our knowledge of diseases and the establishment of technology. Conventional approaches to vaccine development that have emerged over the years have been successful at launching several important vaccines that have undoubtedly saved the lives of many. However, current approaches are not without their limitations.
mRNA vaccines offer a promising alternative to current approaches to vaccine development, their high potency and ability to develop vaccines rapidly at lower cost offers an appealing avenue to explore for future vaccine development. While mRNA vaccines have been in development for a while, they had largely been restricted by their inability to produce the same results in vivo as in vitro. This barrier has been overcome in recent years thanks to significant advances in technology.
Evidence is now emerging from clinical trials that demonstrate the efficacy of novel mRNA vaccine platforms in preventing infectious diseases as well as multiple types of cancer - a chronic disease that is largely out of scope for traditional vaccines. Promising results have been published from pre-clinical and clinical trials.
Advances in mRNA vaccine technology
In recent years, research and development have succeeded in establishing numerous mRNA vaccine platforms, whose efficacy has been confirmed via immunogenicity studies. Synthetic mRNA is now more translatable than ever due to advances in the engineering of the RNA sequence.
Scientists have developed efficient and non-toxic RNA carriers that have been proven in in vivo studies to allow for prolonged antigen expression. Some mRNA vaccine formulations under investigation contain novel adjuvants, while others are adjuvant-free and are designed to elicit potent responses via other routes.
Traditional vaccines have been in development for over 200 years, to date, there has been significant success in the establishment of numerous vaccines that are effective at preventing the spread of certain infectious diseases. However, conventional vaccines have been largely ineffective at preventing challenging viruses, such as those that cause chronic or repeated infections. While scientists have been exploring conventional vaccine platforms for many years, a vaccine against HIV-1, herpes simplex virus, and respiratory syncytial virus (RSV) has not been achieved. Additionally, the development of conventional vaccines is slow, taking many years to process from concept to approval.
Therefore, conventional vaccines are unable to respond to sudden outbreaks of acute viral diseases, such as the Ebola and Zika viruses that devastated countries across the world before the outbreak of COVID-19 at the end of 2019. mRNA vaccines offer a more versatile, dynamic, and potent platform that is needed to prevent the diseases caused by virus outbreaks.
So far, preclinical studies have gathered promising evidence that suggests that mRNA vaccines may be the route to the ideal clinical vaccine. They have a favorable safety profile in animals, can be designed rapidly to respond to emerging diseases, and are scalable - allowing them to be easily mass-produced.
It is hoped that mRNA vaccines will, in the coming years, be established to prevent various kinds of cancer. It is theorized that cancer vaccines could be developed that target antigens presented by tumors. Growth factors and antigens that are unique to cancerous cells would make suitable targets.
Additionally, it is hoped that the research and development underway to create these vaccines may also be successful in developing alternative immunotherapies for these diseases. As a result, we may eventually have effective vaccinations against cancer as well as alternative treatment options which may improve the prognosis and quality of life for certain patients.
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Limitations must first be overcome
Before mRNA platforms can reach their full potential in helping us fight various diseases, several limitations must first be overcome. Further research is required to improve scaling up good manufacturing practice (GMP) production, regulations must be established, and further safety and efficacy evidence must be gathered before new vaccines can obtain approval.
Future directions of mRNA vaccine research will likely focus on comparing the immune pathways activated by numerous mRNA vaccines, enhancing current approaches, and establishing new clinical trials to test mRNA vaccine platforms on new disease targets.
Continue Reading: Role of RNA as a Drug Target
Sources:
- Karikó, K., Muramatsu, H., Ludwig, J. and Weissman, D., 2011. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Research, 39(21), pp.e142-e142. https://pubmed.ncbi.nlm.nih.gov/21890902/
- Kauffman, K., Mir, F., Jhunjhunwala, S., Kaczmarek, J., Hurtado, J., Yang, J., Webber, M., Kowalski, P., Heartlein, M., DeRosa, F. and Anderson, D., 2016. Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo. Biomaterials, 109, pp.78-87. https://pubmed.ncbi.nlm.nih.gov/27680591/
- Pardi, N., Hogan, M., Porter, F. and Weissman, D., 2018. mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery, 17(4), pp.261-279. https://www.nature.com/articles/nrd.2017.243
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