Prof. Maria Rescigno’s Laudatio for the honorary degree awarded to Dr. Katalin Karikó
Prof. Maria Rescigno‘s Laudatio for Dr. Katalin Karikó during the Opening Ceremony of the Academic Year 2021/2022:
“It is my immense pleasure and honor to give this laudatio for Prof. Katalin Karikó”. To quote a title from the New York Times: Dr. Karikó helped ‘shield the world from Coronavirus’. This is because she contributed to develop the technology of mRNA COVID-19 vaccines. Let me indeed give you some numbers to highlight the impact of her findings: In the first six months of 2021, it is estimated that mRNA COVID-19 vaccines have saved 280.000 lives and more than one million of hospitalizations only in the US, without mentioning the avoidance of the economical and psychological consequences of prolonged lockdowns.
What is an mRNA vaccine?
SARS-CoV-2 infects human cells in the nasal and oral cavity by attaching via the SPIKE protein to the ACE-2 receptor on epithelial cells (2). The SPIKE protein is a sort of a key to enter and infect the cell. COVID-19 vaccines induce an immune response, and in particular an antibody response, to the SPIKE protein so to neutralize the virus and impede infection of the cells (3). In this animation (4) you will see how antibodies directed to SARS-CoV-2 work. You can understand now when we talk of shield. There are DNA, RNA or protein vaccines (5). It is like having a mould (DNA), a cast (RNA) and the statue itself of the SPIKE protein. The mRNA vaccine is made of a liposome and an mRNA (6). The liposome conveys the mRNA within the cell. The liposome at the same time protects the very unstable mRNA and allows its penetrance within the cell. Here the mRNA which contains the genetic information to make the SPIKE protein is released and uses the host cellular machinery to make the protein exactly in the same way as the virus would do except that it cannot make the whole virus but only the key protein, so it is totally safe. As you can see here on our healthcare workers population the Pfizer/BioNTech vaccine is very powerful in inducing an antibody response already after the first dose and one dose is sufficient to induce a maximal response in subjects with a COVID-19 history (7). This allowed us to save doses and to provide more vaccines for those who really needed them.
What makes mRNA vaccines so special in comparison to other vaccines?
Despite what many people think, it took more than 30 years to make the mRNA technology to work. Thus, when people argue that the RNA technology is too young and that it is not safe they should talk to Dr Karikó…. Further, before the COVID-19 vaccines, the mRNA-based biologics or vaccines had been tested in clinical trials for several years mostly by Dr Kariko’ and her colleagues in various applications demonstrating safety. But why did it take so long to develop effective RNA-based vaccines? First, stability, RNA as it is found in nature is quickly degraded which makes it safer but also reduces efficacy and second, it could activate immune cells and induce inflammation. Dr Kariko’s studies allowed to solve both problems. After working as an undergraduate on lipids, Dr Kariko’ started working on mRNA by serendipity, as she accepted a PhD position in Jeno Tomasz lab in Hungary. Here, she realized that mRNA could be used as anti-virals. When she went to the US from Hungary she continued working on this concept at Temple University in Pennsylvania. She then tried to use the RNA technology to deliver proteins of interest within the cell and in particular urokinase receptor to treat cardiovascular diseases or cytokines to treat cancer. These studies are still ongoing showing the potential of RNA technology beyond vaccine development.
When Dr Karikó was struggling to make things work, many researchers and companies thought that mRNA was too unstable and expensive to be used as a drug or a vaccine. Even Malone and Meulien who were pioneering the mRNA technology for drug development, gave up and moved into DNA-based vaccines which were more stable. However, Dr Karikò was not discouraged and continued to work on this complex subject because she believed in it. Quoting her words: ‘people felt sorry for me working on RNA, as it is boring and so difficult to work with’. But as many scientists would agree with me now, she took what appeared to be an uphill path but which proved to be the right one. This is a teaching for every student and researcher in this room.
It was in 2005 when the mRNA technology developed by Katalin Karikó and her immunologist colleague Drew Weissman, both at the University of Pennsylvania (UPenn) in Philadelphia, became useful for vaccine development. By substituting uridine, one of mRNA’s nucleotides, with an analogue called pseudouridine, allowed to stop the body identifying the mRNA as a danger and allowed increasing of ten times the amount of protein produced (8). It took however, years for Kati to convince the scientific community and investors that these modifications would move forward the mRNA vaccine field. Her funding proposals were rejected, but she never gave up. Eight years later, in 2013 she went to give a seminar in Mainz Germany on the way back to Hungary from Luzerne, during one of her daughter’s rowing competitions because you should know that Katalin is not the only star in her family. Her daughter Susan Francia is a pluri-Olympic and world rowing champion. In Mainz Katalin met Uğur Şahin the CEO of BioNTech and started working for BioNTech as vice president.
Both Moderna and BioNTech vaccines contain modified mRNA according to the findings of Kati and Drew. This explains why they are the best vaccines in use.
I had the chance to attend – by remote – a seminar given by Dr Karikó at Cambridge University. Besides having really appreciated her sense of humor, after the seminar, she said something very important: people working in science work for the pleasure of making new discoveries, to understand how biology works. It is curiosity that drives our work, no matter how difficult it is to reach achievements. A publication in top-notch journals should not be what drives our science. Solving little problems and sharing of the data is what makes scientists successful. Dr Karikò has remained very humble even after being finally recognized for her fantastic achievements, and for having saved thousands of lives, which is the dream of every scientist in biomedical translational research. She is also a role model for females who want to get into STEM subjects. She says that if you want to be a good scientist you should find the right husband, who is supportive, does not complain about long working hours and learns how to cook. I wouldn’t agree more, but I think that what made Katalin very successful is resilience and courage. She left Hungary in 1985 with around 1200 dollars hidden in a teddy bear, a dream, a passion for science and a 2 years old little girl, she had several stops in her career but never gave up on her mission and made curiosity drive her science.
The mRNA technology that Katalin contributed to establish has far-reaching potential and applications in other fields including cancer vaccines and therapy, from which it actually started, and therapeutic potential for several other disorders. It is a multifaceted technology.
As a scientist, woman and mum, I am very grateful to Katalin for her resilience in science and for driving us out of the pandemic.”