Such vaccines have saved millions of lives and prevented severe disease in many more, allowing societies to open and return to normal conditions
The Nobel Prize for Medicine 2023 has been awarded to Katalin Kariko of Hungary and Drew Weissman of the US. They were awarded for their pioneering work on nucleoside base modifications that enabled the development of effective messenger ribonucleic acid (mRNA) vaccines against COVID-19.
The discoveries and findings by Kariko and Weissman have changed the understanding of how mRNA interacts with human immune systems. It contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.
Genetic information encoded in human DNA is transferred to mRNA in the body’s cell and used as a protein production template. Scientists were able to produce mRNA without cell culture in the 1980s, in a process known as in-vitro transcription.
This also triggered research on how to use mRNA for vaccine and therapeutic purposes. However, in-vitro transcribed mRNA was considered unstable and challenging to deliver, requiring the development of sophisticated carrier lipid systems to encapsulate the mRNA.
Moreover, in-vitro-produced mRNA gave rise to inflammatory reactions.
Karikó and Weissman wanted to test a hypothesis as to whether the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction.
They found that the inflammatory response was almost abolished when base modifications were included in the mRNA. This was in 2005, 15 years before the COVID-19 pandemic.
In further studies published in 2008 and 2010, Karikó and Weissman showed that the delivery of mRNA generated with base modifications increased protein production compared to unmodified mRNA. It also reduced inflammatory responses.
By 2010, several companies were working on mRNA vaccines. After the outbreak of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed.
Protective effects of around 95 per cent were reported, and both vaccines were approved as early as December 2020. Such vaccines have saved millions of lives and prevented severe disease in many more, allowing societies to open and return to normal conditions.
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