mRNA vaccine research wins medicine Nobel

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On the 2nd October, the Nobel prize for medicine and physiology was awarded to Drew Weissman and Kaitlin Karikó for their work which laid the foundations for the mRNA vaccine and consequently led to the development of the Moderna and Pfizer Covid-19 vaccines.

The vaccines they helped to develop have been administered over 13 billion times and saved countless lives.

Vaccines stimulate an immune response against viruses and microbes which can then be stored in memory cells known as T and B cells, allowing for a quicker and stronger response upon reinfection.

Traditional viral vaccines are produced using dead or weakened viruses and more recently, the genetic code for harmless proteins on the surface of viruses, which is delivered to cells via a vector.

The emergence of the Covid-19 pandemic in 2020 resulted in the urgent need for the development of vaccines in order to curb the catastrophic numbers of cases and deaths as well as to return the world to a state of normal.

Conventional vaccine development methods often require large cultures of cells and therefore developing new vaccines using these methods is time consuming, resource-intensive, and expensive: completely unfeasible in the event of a global pandemic.

The vaccines they helped to develop have been administered over 13 billion times and saved countless lives

A previously experimental form of vaccine development using mRNA, the messenger molecule that delivers the information from DNA in order to form proteins, was one such method that had the possibility of rapidly developing new vaccines to tackle SARS-Cov-2.

In mRNA vaccines, fatty nanoparticles deliver the mRNA that encodes protein from the virus. This allows for the mRNA to be processed by the cell’s machinery and the desired protein to be produced in cells of the vaccinated individual.

The protein in question for the Covid vaccines is the spike protein of SARS-CoV-2, located on the outside of the virus and therefore recognisable to the body’s immune system. The presence of this foreign protein within a body cell evokes an immune response that allows the SARS-CoV-2 virus to be recognised and destroyed quickly if a person subsequently becomes infected: rendering the individual immune.

When mRNA vaccines were first researched, it was found that they elicited an undesired inflammatory response and resulted in inefficient protein production.

During Drew Weissman and Katalin Karikó’s research on different types of RNA, they discovered mRNA containing many modified nucleic acids, the building blocks of DNA and RNA, led to a lower stimulation of the inflammatory response and was more stable.

This led to their breakthrough whereby modification of uridine, one of the four building blocks of RNA, to N1-methylypseudo-uridine resulted in a reduced inflammatory response as well as more efficient protein production in cells due to more ribosomes, the cellular protein factories, being occupied at any given time.

Without Weissman and Karikó’s discoveries there would not have been a platform of mRNA vaccine technology to allow for the rapid development of a vaccine

The team also demonstrated that mRNA activates an antiviral protein that protects the cell from invasion by preventing invading viruses from using the cell to produce proteins required for their replication. Interestingly, this was also improved by the modification of mRNA.

Both the Pfizer and Moderna Covid vaccines, which utilise mRNA to provide immunity, contain completely modified uridine bases. The increased protein production and reduced inflammatory responses these mRNA modifications provide, conferred a 95% and 94% protection against symptomatic Covid-19 upon administration of these vaccines in the first clinical trial, respectively, and greatly protected against serious symptoms and death.

A combination of factors led to the rapid response in the development of vaccines against Covid-19: increased funding and resources pumped into projects; a complete revolution of the clinical trial process; the rapid identification and high-resolution structure discovery of the SARS-CoV-2 spike protein; and not to mention the countless scientists and medical professionals involved in the development and testing of the vaccine.

However, it is undoubtable that without Weissman and Karikó’s discoveries there would not have been a platform of mRNA vaccine technology to allow for the rapid development of a vaccine. Therefore, without them, we would be in a position where the number of Covid-19 vaccines produced may have been far lower and may have had a far lesser impact on curbing the pandemic.

Weissman and Karikó’s work extends far beyond the Covid-19 pandemic. They have paved the way for many new vaccines to be developed. Even before the pandemic, modified mRNA vaccines were in the process of being developed for Zika virus, MERS-CoV, types of avian flu and influenza and more recently, multiple cancers as well as many other infectious diseases.

Weissman and Karikó’s work has proved the possibility of rapid vaccine development as a reality; further equipping the arsenal of technologies available to scientists which will hopefully help prevent any of us living through a pandemic again.

Illustration: Niklas Elmehed © Nobel Prize Outreach 

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