The 2023 Nobel Prize in Physiology or Medicine has been jointly awarded to Katalin Kariko from Hungary and Drew Weissman from the US “for their discoveries concerning nucleoside base modification that enabled the development of effective mRNA vaccines against COVID-19”. The Royal Swedish Academy of Science announced the Nobel Prize on October 2, 2023.
According to the Nobel Prize website, these findings have changed the perception of the world about how messenger RNA (mRNA) interacts with the human immune system. Katalin Kariko and Drew Weissman’s work has contributed to the extraordinary rate of vaccine development during one of the greatest threats to health in modern times (the COVID-19 pandemic).
Development of mRNA Vaccines
As a template for protein production in the cells of human body, genetic information encoded in the DNA is transferred to mRNA. Production of mRNA without cell culture was introduced, using efficient methods, in 1980s, known as the in vitro transcription. This step led to the development of molecular biology applications in several fields. Though it paved the way to the vaccine development using mRNA for therapeutic purposes, there were many obstacles too. Then, the in vitro-transcribed (lab-developed) mRNA was considered to be unstable and challenging to deliver. The need for developing a sophisticated carrier lipid systems was felt to encapsulate the mRNA. Further, there were inflammatory reactions due to in vitro-produced mRNA. Therefore, zeal for developing mRNA technology for clinical purpose could not emerge.
However, Katalin Kariko dedicated herself in developing methods to use mRNA for therapy. Despite encountering difficulties in convincing research funders funding for her research on mRNA for therapeutic use, she continued her research during the 1990s. She was then joined by immunologist, Drew Weissman, who was interested in dendritic cells, which have important functions in immune surveillance and the activation of vaccine-induced immune responses. They both collaborated and researched on how different RNA types interacted with the immune system.
Contributions of Katalin Kariko and Drew Weissman
During their research, Kariko and Weissman observed that dendritic cells recognised in vitro-transcribed mRNA as a foreign substance, which led to their activation and release of inflammatory signalling molecules. However, when animal cell assays were used, it did not release inflammatory signalling molecules. They looked for the reasons why lab-developed mRNA molecules tripped off the immune system. It was found that the mRNA derived from the animal cell assays usually held several modifications which were invisible in the lab-developed uniform mRNA molecules. They experimented different variants of mRNA, each with unique chemical alterations in their bases. This was then delivered to dendritic cells. They succeeded in almost eliminating inflammatory response when base modifications were included in the mRNA. In their subsequent studies, the altered mRNA efficiently generated more viral proteins as compared to unaltered ones. This led to the recognition of how cells recognised and responded to different forms of mRNA. Kariko and Weissman realised that their discovery had great importance for using mRNA as therapy. Their seminal results were published in 2005, which was decade and a half before the COVID-19 pandemic.
Significance of mRNA Vaccines during COVID-19
Traditional vaccines used to introduce dead or weakened viruses into the human body in order to develop antibodies against them. Thus, when the actual virus infects the human body, it is ready to fight it. With the evolution in technology, only a part of the viral genetic code was introduced through vaccines in place of the whole virus. However, large-scale development of such vaccines required cell culture, which is a time-consuming affair.
In 2010, several companies began to work on developing vaccines with mRNA technology, such as vaccines against Zika virus and MERS-CoV.
When the COVID-19 outbreak happened, it was very crucial to find a vaccine to curtail the deadly and fast-spreading virus. After the outbreak of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed expeditiously. These vaccines had a protective efficacy of about 95 per cent, and hence, were approved by December 2020.
Several other vaccines against SARS-CoV-2 based on different methodologies were promptly introduced using this mRNA technology. More than 13 billion COVID-19 vaccine doses have been administered worldwide. These mRNA vaccines not only saved millions of lives, but also prevented severe disease and allowed the world to return to normal conditions soon.
The 2023 Nobel laureates, Kariko and Weissman, contributed immensely for the development of COVID-19 vaccines through their fundamental discoveries on the importance of base modifications in mRNA. Their work helped in averting millions of deaths due to the viral infection and helped the world recover from the worst pandemic of the century.
The momentum with which the mRNA vaccines were developed has paved the way for using this new platform for vaccines against other infectious diseases. Research is being done to deliver therapeutic proteins and treat some types of cancers using this technology.
Nobel Prize in Medicine
The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at Karolinska Institute, Stockholm, Sweden. The prize carries a cash award of 11 million Swedish Kronor and would be awarded to the laureates on December 10, 2023 at Stockholm, Sweden, on the anniversary of Nobel’s death. The prize would be shared between the laureates equally. The money comes from a bequest left by Swedish inventor Alfred Nobel, who died in 1895.
Winners of Nobel Prizes in 2023 will get an extra 1 million crowns, taking the total financial reward to 11 million Swedish kronor.
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