Wednesday, November 29, 2023

Nobel Prize for Medicine 2023 – The time was ripe: pioneers of mRNA vaccines honored

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The Nobel Prize in Medicine goes to two researchers, without whose work the mRNA vaccines against Corona would not exist.

Vaccines against flu, proteins to repair damaged tissue – perhaps even new therapies against cancer. mRNA technology promises all of this.


Katalin Karikó and Drew Weissman

Image: University of Pennsylvania-Peggy Peterson

Hungarian researcher Katalin Karikó and her American colleague Drew Weissman were today named winners of this year’s Nobel Prize in Medicine for their groundbreaking research in this field.

What is mRNA technology?

mRNA is the blueprint that the human cell needs to produce proteins. With artificial mRNA, the body can be made to produce any protein imaginable – including those for vaccines. Biologists have had the idea for a long time.

The mRNA technology passed its practical test when the world was overrun by the corona virus. Researchers can present effective vaccines in record time, and somewhere between hope and skepticism, people around the world are being vaccinated with artificial mRNA. It causes the body to produce a faithful copy of the famous spike protein that sits on the surface of the corona virus. Thanks to this copy, the immune systems of millions of people now know how to fight the corona infection quickly and effectively.

The fact that the vaccine is being developed at all is not thanks to the companies Biontech or Moderna, but to the two new Nobel Prize winners. Katalin Karikó, who brings enormous knowledge in the field of mRNA research, and the immunologist Drew Weissman, have been working together at Pennsylvania University since the early 1990s. They want to develop an mRNA vaccine against HIV.

Researchers hit a wall

But there is a problem, a wall that researchers keep running into: the artificial mRNA is unstable and breaks down before a protein can be built. It causes the immune system to overreact and causes inflammation. In addition, the cells produce too little of the desired protein. A vaccine cannot be developed on this basis.

More about Katalin Karikó and Drew Weissman

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The Hungarian Katalin Kariko is born in 1955. She studies at Szeged University, where she also receives her doctorate. As a postdoc, she first conducted research in Hungary and then in the USA. In 1989, the biochemist received an assistant professorship at the University of Pennsylvania, where she met the immunologist Drew Weissmann and conducted research with him since the early 1990s.

Karikó’s research has long been unrecognized. She never receives large amounts of funding and therefore cannot set up her own research group. In 2013 she had to leave the University of Pennsylvania and moved to BioNTech RNA Pharmaceuticals until 2022. Since 2021 she has been a professor at the University of Szeged and an associate professor at the University of Pennsylvania.

Drew Weissman was born in 1959 in Massachusetts, USA. He received his PhD from Boston University, followed by clinical training at Harvard Medical School and research at the National Institutes of Health. The immunologist founded his research group in 1997 at the University of Pennsylvania, where he still works. He is a professor of vaccine research and director of the Penn Institute for RNA Innovations.

Karikó and Weissman didn’t give up and finally made a crucial discovery, which they published in 2005: They found a way to introduce mRNA into the body without causing the immune system to overreact.

Diverse achievements

In the test tube, they replace uridine, one of the four bases that make up mRNA, with the modified base pseudouridine. The four bases are, so to speak, the letters with which the mRNA encodes the building instructions for a protein. They often occur in different modifications in the human body, including pseudouridine. And lo and behold! It works! The wall that the researchers have been running against for so long is crumbling: If the researchers use artificial mRNA with pseudouridine, the immune system remains calm, there is no inflammation, and at the same time more proteins are produced in the cell.

All of this would be useless if the mRNA cannot get into the cells. Karikó and Weissman once again show their research spirit: They pack the sensitive mRNA molecules in lipid shells so that they pass through the cell membrane into human cells.

This is how the most common vaccinations work

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Our body can be stimulated in various ways to build up a defense against pathogens – viruses or bacteria. This is how the most common vaccinations work.

Dead or live vaccines: They contain a weakened or inactive form of the virus that the vaccination is intended to protect against. Examples are: the MMR (mumps-measles-rubella) vaccine, the polio (polio) vaccine.

Protein vaccines: Contain specific proteins of a pathogen or fragments thereof. An example: hepatitis B. Once in the human body, these proteins trigger an immune response.

DNA vaccines: Use genetic material from the pathogen, i.e. its DNA. One example is the Ebola vaccine: a single gene from the Ebola virus is introduced into the harmless VS virus. The virus modified in this way penetrates the body’s cells, which then produce the Ebola-specific protein. The protein in turn triggers the immune response in humans.

mRNA vaccines: mRNA – the building instructions for proteins – is produced artificially. The Covid-19 vaccines contain the construction instructions for a surface protein of the Covid-19 virus (spike protein). When the mRNA enters the human cells, the virus protein is produced and an immune response is triggered.

Thanks to this preparatory work, the time is ripe when vaccination against Sars-CoV-2 will be needed in 2020. “It was only with the Covid pandemic, where it was important that a new vaccine was developed very quickly, that this technology showed its huge advantage,” says Christoph Berger, immunologist at the University of Basel. “You can develop a vaccine with mRNA technology within weeks, which takes much longer with other technologies.”

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