Il Nobel prize for Medicine 2023 it was awarded to Katalin Kariko e Drew Weissman for the discoveries that allowed the development of vaccines anti-Covid which, writes the Nobel Assembly at the Karolinska Institutet, “have saved millions of lives and prevented serious diseases, allowing societies to open up and return to normal conditions” of existence. “Through their fundamental discoveries on the importance of basic modifications in mRNA, this year’s Nobel laureates have crucially contributed to this transformative development during one of the greatest health crises of our time.”
This is why it was decided to award the prize “jointly” to those who can be considered the “parents” of mRna vaccines, Katalin Karikó and Drew Weissmanwith this official motivation: «For their discoveries regarding the modifications of the nucleoside bases which have allowed the development of effective mRNA vaccines against Covid».
Discoveries, the experts of the Nobel assembly highlight in the official note, which “were fundamental for the development of mRna vaccines during the pandemic that broke out at the beginning of 2020″. And “revolutionary”, because “they have radically changed our understanding of how mRNA interacts with our immune system”. Thus the winners of the 2023 Nobel Prize in Medicine “have contributed to the unprecedented pace of vaccine development during one of the greatest threats to human health of modern times”.
The 2023 #NobelPrize in Physiology or Medicine has been awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. pic.twitter.com/Y62uJDlNMj
— The Nobel Prize (@NobelPrize) October 2, 2023
Vaccines before the pandemic
Vaccination stimulates the formation of an immune response towards a particular pathogen. This gives the body an advantage in fighting disease in case of subsequent exposure. Vaccines based on killed or weakened viruses have been available for some time, as in the case of vaccines against polio, measles and yellow fever. In 1951, Max Theiler received the Nobel Prize in Physiology or Medicine for developing the yellow fever vaccine.
Thanks to the progress of molecular biology In recent decades, vaccines have been developed based on individual viral components, rather than whole viruses. Parts of the viral genetic code, which usually code for proteins on the surface of the virus, are used to produce proteins that stimulate the formation of antibodies that block the virus. Examples are vaccines against hepatitis B virus and human papillomavirus. Alternatively, parts of the viral genetic code can be moved into a harmless carrier virus, a “vector.” This method is used in Ebola vaccines. When vaccine vectors are injected, the selected viral protein is produced in our cells, stimulating an immune response against the target virus.
The production of vaccines based on virus, proteins and whole vectors requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to epidemics and pandemics. Therefore, researchers have long attempted to develop cell culture-independent vaccine technologies, but this has proven challenging.
The turning point
Karikó and Weissman noted that dendritic cells recognize in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules. They wondered why mRNA transcribed in vitro was recognized as foreign while mRNA from mammalian cells did not give rise to the same reaction. Karikó and Weissman realized that some critical properties must distinguish different types of mRNA.
Drew Weissmann, who is the scientist who won the Nobel Prize for Medicine
RNA contains four bases, abbreviated A, U, G and C, corresponding to A, T, G and C in DNA, the letters of the genetic code. Karikó and Weissman knew that bases in mammalian cell RNA are often chemically modified, while in vitro-transcribed mRNA is not. They wondered whether the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction. To investigate this, they produced several mRNA variants, each with unique chemical alterations in their bases, which they delivered to dendritic cells. The results were surprising: the inflammatory response was almost abolished when the base changes were included in the mRNA. This was a paradigm shift in our understanding of how cells recognize and respond to different forms of mRNA. Karikó and Weissman immediately understood that their discovery had profound significance for the use of mRNA as a therapy. These landmark findings were published in 2005, fifteen years before the COVID-19 pandemic.