“Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times,” the Nobel Prize website said.
Who are Katalin Kariko and Drew Weissman, and how did their work contribute to the development of Covid vaccines?
What are mRNA vaccines, why they were crucial during Covid
Traditionally, vaccines have depended on introducing dead or weakened viruses into the human body, so it can develop antibodies against them. Thus, when the actual virus infects someone, their body is prepared to fight it. As technology evolved, instead of the whole virus, just a part of the viral genetic code, instead of the whole virus, began to be introduced through vaccines. But the large-scale development of such vaccines requires cell culture (growing of cells under controlled conditions) and takes time.
During the Covid-19 outbreak, time was of the essence in finding a weapon against the deadly and fast-spreading virus. This is where mRNA technology proved crucial.
This technology had been known since the 1980s, but had not been perfected enough to create vaccines at a viable scale. Basically, instead of putting an inactivated virus in the body to activate an immune response, vaccines using this technology use messenger Ribonucleic Acid, or mRNA, to deliver a message to the immune system. Genetically engineered mRNA can instruct cells to make the protein needed to fight a particular virus. Since RNA is already present in cells, this method does away with the need for cell culture.
What Kariko and Weissman did
According to the Nobel Prize website, Karikó and Weissman realised that the problem with such genetically engineered mRNA is that the body’s dendritic cells [which have important functions in immune surveillance and the activation of vaccine-induced immune response] recognise them as a foreign substance, and release inflammatory signaling molecules against them.
“Karikó and Weissman knew that bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not. They wondered if the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction. To investigate this, they produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells. The results were striking: The inflammatory response was almost abolished when base modifications were included in the mRNA,” the website says.
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These results were published in 2005, and the two further built on their work in 2008 and 2010. Thanks to these findings, work on mRNA vaccines was already underway, and this turned out to be really helpful when the scramble for a Covid vaccine was on. Moderna and Pfizer vaccines used this technology.
Kariko and Weissman before the Nobel
According to the Nobel website, “Katalin Karikó was born in 1955 in Szolnok, Hungary. She received her PhD from Szeged’s University in 1982 and performed postdoctoral research at the Hungarian Academy of Sciences in Szeged until 1985. In 1989, she was appointed Assistant Professor at the University of Pennsylvania [where Weissmanwas her colleague, where she remained until 2013. After that, she became vice president and later senior vice president at BioNTech RNA Pharmaceuticals. Since 2021, she has been a Professor at Szeged University and an Adjunct Professor at Perelman School of Medicine at the University of Pennsylvania.”
Drew Weissman “was born in 1959 in Lexington, Massachusetts, USA. He received his MD, PhD degrees from Boston University in 1987. He did his clinical training at Beth Israel Deaconess Medical Center at Harvard Medical School and postdoctoral research at the National Institutes of Health. In 1997, Weissman established his research group at the Perelman School of Medicine at the University of Pennsylvania. He is the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovations.”
