The development of conventional vaccines takes 1-15 years, while the COVID-19 messenger RNA (mRNA) vaccines – Pfizer and Moderna – took less than a year to be approved. Naturally, many were concerned and had questions, how was it possible to create a “new” type of vaccine in such a short time? In this article, we will briefly discuss the history that leads to the rapid – yet successful – development of the COVID-19 mRNA vaccines.
Our cells use mRNA to produce specific protein products (more information here). However, outside of cells, mRNA is unstable. The immune system perceives extracellular mRNA as an indication of a viral infection.
In 1987, Robert Malone first discovered that mRNA could be more stable if it was protected inside a fat droplet. When this fat-mRNA complex is applied to human cells, the mRNA enters the cells and starts protein production. These results allowed Malone to realize the potential to “use RNA as a drug” and he later became the first researcher to use fatty droplets to deliver mRNA into a living organism. Even though Malone proved the potential to “use RNA as a drug,” mRNA vaccines still faced many challenges, such as producing stable mRNA; and developing safe and efficient delivery vehicles [1].
The first commercial research and development company focused on mRNA, Merix Biosciences, was founded in 1997 [1]. Later, BioNTech (Pfizer) and Moderna, founded in 2008 and 2010 respectively, used the mRNA technology to develop a vaccine for COVID-19 [2]. As a fun fact, the name of the company “Moderna” comes from “modified” and “RNA”. This is because the company is focused on developing drugs based on RNA [3]. In 2012, a Pieter Cullis’s laboratory developed a lipid nanoparticle for mRNA delivery [2]. Step by step research progress allowed the first mRNA vaccine for rabies finally entered clinical trials in 2013 [2]. In the subsequent year, Ebola virus, originally discovered in 1976, became epidemic and swept across West Africa [4]. This outbreak stimulated the approval of clinical use of the long-studied Ebola vaccination as the first mRNA vaccine delivered in lipid envelope in 2019 [4,5].
When COVID-19 pandemic hit, Moderna created a mRNA vaccine prototype, conducted mouse studies, and launched human trials with the US national Institute of Allergy and Infectious Disease in less than ten weeks after the viral genome sequence became available [1]. At the same time, BioNTech, in collaboration with Pfizer, produced a mRNA vaccine that entered clinical trials and received emergency approval in less than eight weeks [1]. For more information about how these vaccines work, you can read the post “Decoding the COVID-19 mRNA vaccine”. Check out the image below for a more detailed history of mRNA vaccine development.
Figure 1. The history of mRNA vaccines [1].
Thus, the answer about how it was possible to make the COVID-19 mRNA vaccine in a shorter time than previous vaccines is not a miracle nor a “short-cut”. Scientists have been working behind the scenes, researching for safe and effective mRNA technology in the past three decades. Once they proved that mRNA vaccine was safe and successful for Ebola, it was relatively easy to apply the same principles to create a new vaccine for COVID-19. In fact, since the pandemic many researchers are investigating the use of mRNA vaccines for other diseases like HIV, influenza, Zika, and even cancer [6, 7]; leading to a new era for vaccine technology and production.
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Written by: Hedi
Edited by: María and Natasha
BioDecoded is a volunteer group committed to sharing accurate scientific information. For more information about vaccines and their safety profile, please see previous posts or consult with your personal physician. If you have any questions about this topic, please comment or send them to our email.
References:
Dolgin E. The tangled history of mRNA vaccines. Nature. 2021;597(7876):318-324. Available at: https://pubmed.ncbi.nlm.nih.gov/34522017/
Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater 2021 612. 2021;6(12):1078-1094. Available at: https://www.nature.com/articles/s41578-021-00358-0
About us. Moderna (2022). Available at https://www.modernatx.com/about-us/our-story (Accessed: 1 June 2022).
Feldmann H, Jones SM, Daddario-DiCaprio KM, et al. Effective post-exposure treatment of ebola infection. PLoS Pathog. 2007;3(1):0054-0061. Available at: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0030002
First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response. FDA (2020). Available at: https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health (Accessed: 1 June 2022).
More than COVID-19: 6 other promising mRNA vaccines in the pipeline. GoodRX Health (2021). Available at: https://www.goodrx.com/health-topic/vaccines/other-mrna-vaccines (Accessed: 1 June 2022).
Pardi, N. et al. (2018) “mRNA vaccines — a new era in vaccinology”, Nature Reviews Drug Discovery, 17(4), pp. 261-279. Available at: https://www.nature.com/articles/nrd.2017.243#Sec10
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