“Through their groundbreaking findings, the laureates contributed to the unprecedented pace of vaccine development during one of the greatest threats to human health in modern times,” writes the Nobel Committee: The 2023 Nobel Prize in Medicine goes to Katalin Karikó and Drew Weissman for their mRNA -Research that led to the development of the novel Covid-19 vaccine. Their fundamental contribution was a special modification of the mRNA, through which these messenger molecules can be transformed into effective vaccines.
Vaccines prepare our immune system for attackers so that it can quickly turn its weapons on bacteria, viruses, etc. The immune system recognizes certain building blocks of the pathogens and forms antibodies against these elements. In this way, it learns to quickly identify the pathogens and react to them. There are different ways to achieve this effect. The oldest vaccine concepts are based on dead or rendered harmless viruses.
In recent decades, however, new types of vaccines have been developed in which the whole pathogen is no longer used, but only parts. These can, for example, be proteins produced in the laboratory that the pathogens normally carry on their surface. This principle is used, for example, in vaccinations against hepatitis B and the human papilloma virus (HPV). The immune system can also be trained by introducing parts of the genetic material of a pathogen into another, harmless carrier virus. This carrier, called a “vector,” transports the genetic information for the blueprint of certain viral proteins into human cells, where they are produced and trigger a response from the immune system. This type of vaccine is used, for example, against Ebola.
mRNA vaccines save time
Since the corona pandemic, however, there has been another new type of vaccine: the mRNA vaccine. They are based on mRNA, which enters human cells directly without a vector, which then produces pathogen proteins and triggers an immune reaction. It is precisely these vaccines that we ultimately owe to the Nobel Prize winners for medicine Katalin Karikó and Drew Weissman, because they laid the foundations for their development and their millions of uses. Unlike the previously common vaccines with whole viruses, viral proteins or vectors, the mRNA vaccines no longer require large cell cultures to produce and can therefore be produced significantly faster and with fewer resources. In epidemics and pandemics such as the recent Sars-CoV-2 coronavirus, this is a decisive advantage in being able to quickly support people's immune systems.
The mRNA (messenger RNA) is a type of molecule that serves as an information carrier in our cells. It passes on the genetic information on our DNA to the production sites in the cells so that they can use it to make proteins. Since the 1980s, mRNA has also been able to be produced synthetically. However, it was initially too unstable to produce vaccines and led to inflammation. The two Nobel Prize winners were able to solve this problem as part of their research work. The Hungarian biochemist Katalin Karikó set herself the goal of using artificial mRNA therapeutically in the early 1990s. As an assistant at the University of Pennsylvania, she and her colleague, immunologist Drew Weissman, researched how mRNA interacts with the various cells of our immune system.
At the beginning of the path to mRNA vaccines
Karikó and Weissman discovered that synthetically produced mRNA is recognized as foreign to the body by so-called dendritic cells. This causes our immune system to release substances that promote inflammation. The two Nobel Prize winners continued their research and deciphered how the artificial mRNA differs from our body's own mRNA. It turned out that the two types of mRNA are made up of the same building blocks, which are abbreviated with the letters A, U, G and C. In our bodies, however, these bases are chemically modified naturally; this was not initially the case with the building blocks of the artificially produced mRNA. When Karikó and Weissman also incorporated modified bases into the synthetic mRNA, the dendritic cells of the immune system no longer responded with inflammation. “This was a paradigm shift in our understanding of how cells recognize and respond to different forms of mRNA,” said the Nobel Committee, explaining its decision to award the two researchers the Nobel Prize.
Nevertheless, it would still be years before mRNA could be used in vaccines. Karikós and Weissman's first discovery was published in 2005. In 2008 and 2010 they then presented two further studies in which they showed that proteins can be effectively produced from the artificial mRNA with modified bases, just as happens naturally in our bodies. This was an essential prerequisite for later producing viral proteins from viral mRNA.
Extensive potential
From then on, several companies researched the use of mRNA vaccines, initially against the Zika virus and the Mers-CoV coronavirus. With the outbreak of the corona pandemic caused by the Sars-CoV-2 coronavirus at the beginning of 2020, an mRNA vaccine was developed for the first time against a novel and previously unknown pathogen. Two such mRNA vaccines were approved in December 2020. This made it the fastest vaccine development in history, but it would not have been possible without the decades of research by Káriko and Weissman.
The development of mRNA vaccines against Covid-19 also opens up new possibilities for other applications. Their use in other infectious diseases, but also against some types of cancer, is being researched. But they have already saved millions of lives and enabled society to cope with the corona pandemic. “Through their fundamental discoveries about the importance of base modifications in mRNA, this year's Nobel Prize winners have made a decisive contribution to this transformative development during one of the greatest health crises of our time,” writes the Nobel Committee.
Source: Nobelprize.org