mRNA vaccines: the innovation brought to the market by COVID-19

An extremely short period of time has passed since the first case of pneumonia with unknown aetiology was officially registered in December 2019 in Wuhan, China, and the market authorization of the first vaccine against SARS-CoV-2 in December 2020. [1,2] (for more on this, read here the previous blogpost of this series).

While the supercharged funding was essential for the speedy delivery of COVID-19 vaccines development, it is important to remember that the research underpinning their development started before January 2020. [1]

At time of writing, four COVID-19 vaccines have been approved in the UK. Two are built on mRNA-based technology and two on inactivated Adenovirus (non-replicating virus vaccines). While other adenovirus-based vaccines have been approved before, these are the first mRNA-based vaccines to hit the UK market.

How do vaccines work?

Vaccines train our bodies to fight harmful diseases. They do this by stimulating our immune system to create protective antibodies against a disease without being exposed to the disease itself. To do so, vaccines introduce the immune system to a substance that it can then respond to: this is called an antigen. The trained immune system can then act swiftly when it is finally exposed to the real pathogens. [3]

Throughout history, different approaches have been used to deliver antigens in a safe and efficient way. Conventional approaches use some form of weakened pathogens or fragments of their proteins or sugars that they have on their surfaces.[4] However, new approaches have been developed and applied to COVID-19, such as mRNA vaccines.

Photo by Spencer Davis on Unsplash

Messenger RNA

Three main macromolecules direct how living organisms function and work: DNA, RNA and proteins.

DNA is the ‘long-term storage’ of all the genetic information. It forms a massive instruction manual for how to build the blocks that allow our cells to function properly. Each cell in your body contains the same DNA.[5]

RNA is the ‘messenger’ (hence the ‘m’ in ‘mRNA’!). Relevant parts of the DNA are recognized and read by complex machinery in each cell of our body and transcribed into mRNA. The mRNA brings the genetic message to the production machinery to put together protein.

Proteins are the final molecular products that do the work of building and maintaining your cells.

The mechanism of action of mRNA vaccines

Instead of injecting a weakened pathogen or an antigen itself, mRNA vaccines simply deliver the ‘instructions’ to make an antigen protein. In the case of SARS-CoV-2, the mRNA in the vaccine tells your cells to build a small part of the virus’ ‘spike protein’, which your body’s immune system detects and responds to, leading to immunity against the real virus.[4]

Synthetic mRNA can potentially be designed to produce any protein, and its manufacture is much simpler than with protein vaccines or inactivated virus vaccines.[1] RNA vaccines have been investigated for a while but the technology was not ready for application until approximately 5 years ago.[1] Indeed, in 1990 scientists had used RNA encoding an influenza antigen in mice,[4] and further studies have been done on other infectious diseases such as rabies and Zika, but none passed early-phase clinical trials. [6]

For a cool video explaining mRNA COVID-19 vaccines as ‘fork hands’ please see this TikTok video by hotvickkrishna

RNA vaccines come with a few challenges. The mRNA molecule is quite unstable and is naturally degraded quite fast. Moreover, injecting mRNA directly inside humans or other animals could trigger a rather serious inflammatory response. However, since the early 2000s, a few key technological advances have contributed to the successful production of safe and effective SARS-CoV-2 mRNA vaccines, making them more stable and safe when delivered into the body’s cells. [6] 

Photo created by kjpargeter- www.freepik.com

What does this mean for the future?

The use of RNA technology is very attractive for the development of future vaccines, especially for diseases that have proven particularly difficult for vaccine development like malaria and tuberculosis.[1] RNA simplifies the manufacturing process as a single factory can be used to produce different vaccines at the same time. Furthermore, the RNA sequences themselves can be easily modified for future pandemics, or new strains of current diseases. [1]

Interestingly, there is already talk of using the same RNA technology for completely different, non-infectious diseases like cancer. The idea behind this is simple: mRNA vaccines would carry the information to encode a specific tumour antigen and stimulate the immune response against the cancer cells. [8]

While the vaccine response derived by the COVID-19 pandemic seem to have opened the doors to new therapeutic possibilities based on mRNA technologies, we should always remember that scientific breakthrough doesn’t happen overnight, but it is the result of years of studies and overcoming technological challenges. 

References

1.Ball, P. What the lightning-fast quest for covid vaccines means for other diseases. Nature, 589, 16-17 (2021)

2.Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020).

3.WHO. How do Vaccines work?  shorturl.at/lBERV WHO (Accessed May 2021)

4.Dolgin, E. How COVID unlocked the power of RNA vaccines. Nature 589, 189-191 (2021)

5.Lodish, D et al. Chapter1: Molecular Biology. Central Dogma of Biology: Classic View 4th edition, 2000

6.Kwon, D. The Promise of mRNA Vaccines. The Scientist (Accessed April 2021)

7.Wardell, C.M., Levings, M.K. mRNA vaccines take on immune tolerance. Nat Biotechnol 39, 419–421 (2021).
8. Miao, L., Zhang, Y. & Huang, L. mRNA vaccine for cancer immunotherapy. Mol Cancer 20, 41 (2021).