The 2023 Nobel Prize in Physiology or Medicine is shared between Katalin Karikó and Drew Weissman for their discovery of nucleoside base modification that enables the development of mRNA vaccines. Pfizer, BioNTech, and Moderna have used the technology to develop their Covid vaccines in 2020. The researchers join a total of 11 laureates at the University of Pennsylvania who have received the Nobel Prize in Medicine or Physiology.
The world breathed a sigh of relief in November 2020 when Pfizer and partner BioNTech showed an efficacy of about 95 percent against Covid-19 with its mRNA-based vaccine candidate BNT162b2. Moderna followed, showing similar efficacy results with its candidate mRNA-1273 .
Vaccination is a proven method of strengthening the body’s immune defences against infectious diseases. In the past, vaccines containing dead or attenuated viruses, such as polio, measles and yellow fever, were the standard. With advances in molecular biology, new manufacturing methods have been developed. Instead of using whole viruses as immune stimulants, scientists can use specific parts of a virus’s genetic code, either DNA or RNA.
These new COVID-19 vaccines use specific messenger RNA (mRNA) sequences to smuggle instructions into cells for building viral protein. These cells are then taught to temporarily produce the viral protein and recognise it in the future. This means that when a vaccinated person is exposed to that virus, the immune system is ready for action – in other words, antibodies are created. The most successful example of how the technology can be used is the vaccines developed against the novel coronavirus.
Both medical and monetary successes
Pfizer/BioNTech and Moderna and several other pharmaceutical companies that have used mRNA technology to develop vaccines against Covid-19 have had great success. The success has not been limited to the realm of medicine – Pfizer, for example, recorded vaccine revenues of just under 43 billion USD in 2021. In second place is the German partner BioNTech, which in the same year had vaccine revenues of just over 22 billion USD. Read more here.
The researchers behind the discovery
These companies have two researchers to thank for their successes – not to mention the millions of people who have been vaccinated against Covid-19. Katalin Karikó, 68 years old and professor at both Szeged University in Hungary and University of Pennsylvania and senior vice president at BioNTech, and Drew Weissman, 64 years old and director of the Penn Institute for RNA Innovations.
The Nobel Prize in Physiology or Medicine has been awarded 114 times to 227 scientists between 1901 and 2023. Yesterday, October 2, the Nobel Assembly announced that this year’s laureates in the category are Katalin Karikó and Drew Weissman. Thus, a total of 29 laureates have originated from Penn, of which 11 in the category of physiology or medicine.
In a press release, the Nobel Assembly justified its choice of laureates:
“The discoveries by the two Nobel Laureates were critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020. 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.”
Nucleoside base modification
Initially, mRNA technology gave rise to inflammatory reactions, which is why enthusiasm for using the technique for clinical purposes was limited. This changed when Weissman and Karikó made their groundbreaking discoveries. They created different variants of mRNA with different base modifications and delivered them to dendritic cells. This resulted in a sharp decrease in the undesirable inflammatory reaction. This discovery, published in 2005, played a central role in the development of effective mRNA vaccines.
In later studies from 2008 and 2010, Karikó and Weissman showed that base-modified mRNA also increased the production of protein compared to non-modified mRNA. Their research paved the way for the use of mRNA in clinical contexts, but it took until the COVID-19 pandemic before the first vaccines based on their discoveries were developed. When the pandemic broke out, the above-mentioned two mRNA vaccines with base modifications, which coded for the surface protein of the virus, could be developed rapidly and begin to be used on an industrial scale.