Drew Weissman and Katalin Kariko were announced as winners of the Nobel Prize in Physiology or Medicine earlier this month. They have been recognised for their mRNA research, which formed the basis for COVID-19 vaccine development. They will receive their prizes at a ceremony in Oslo on 10th December.
Who are Drew Weissman and Katalin Kariko?
The pair met at the University of Pennsylvania in 1997, long before the COVID pandemic. Kariko, a biochemist, and Weissman, an immunologist, were both working on RNA and decided to collaborate and explore its therapeutic uses. The major stumbling block was administering the RNA to the body. Injected mRNA would often be degraded before reaching its target or would trigger an adverse inflammatory response. They solved these issues by delivering the mRNA packaged into lipid nanoparticles and replacing one of the bases in the mRNA to make it more stable.
Kariko’s story is particularly remarkable. Born into Communist-era Hungary to working-class parents, she was once coerced into working as an intelligent asset for the Communist government, although she insists she never gave them any information. In 1985, her lab in Hungary lost funding. She moved to the USA with her family, smuggling cash in her daughter’s toys. A few years later, when she was applying for a new job at Johns Hopkins, her employer threatened to have her deported if she took the new position. While she fought the extradition case, Johns Hopkins retracted the job offer. Starting at the University of Pennsylvania in 1989, her research into mRNA therapies was often met with skepticism in the scientific community. She then moved to work at BioNTech RNA Pharmaceuticals, using the approaches she pioneered in their COVID-19 vaccine. The Moderna vaccine also used mRNA methods.
Estimates show that COVID-19 vaccinations saved nearly 20 million lives in their first year. mRNA vaccinations are also being developed by Moderna against 15 other pathogens with the potential to cause a pandemic.
Vaccines explained:
In cells, mRNA is the intermediate step between DNA and proteins. DNA in the nucleus encodes a messenger RNA which then leaves the nucleus and is translated to form a protein. mRNA vaccines against COVID-19 introduce the code for the spike protein found on the SARS-CoV-2 virus. This way, the immune cells are introduced to the antigen safely and can prepare for the real virus. Immune memory cells will then trigger a more rapid and targeted response when the real virus enters the body.
mRNA vaccines proved advantageous for COVID-19, as they are relatively quick and cheap to develop. The Pfizer/BioNTech vaccine costs an estimated $1.18 per dose to manufacture, although it is sold at a considerable markup.
Other vaccines work by the same principle of preparing the immune system for later infection. Traditional vaccines involve the injection of weakened or inactivated parts of the pathogen. Most of the ‘well-known’ vaccines, including measles, mumps, rubella, and tuberculosis are attenuated vaccines. Attenuated vaccines contain a live but weakened form of the pathogen. The pathogen is attenuated (weakened) through repeat infections in a series of hosts in the lab, eventually weakening the virus as it no longer needs to be as invasive to survive. Inactivated vaccines were developed over a hundred years ago for cholera and typhoid. The pathogen is killed by heat or chemicals then part of, or the whole of, the pathogen is injected to trigger an immune response.
Vaccination has a long and very successful history. Starting in the 18th Century, Edward Jenner is credited with the first vaccine. He showed that inoculating someone with pus from cowpox blisters could prevent smallpox. Nearly 200 years later in 1980, the World Health Organization (WHO) declared smallpox had been eradicated around the world. Through vaccination, rabies has been virtually eliminated in the UK, with only four recorded cases this century. The WHO estimates that vaccination now prevents up to five million deaths per year.
The University of Sheffield is also involved with mRNA vaccine developments. In 2021, Dr Zoltán Kis received a grant from Wellcome Leap (an arm of the Wellcome Trust) to fund research into other potential mRNA vaccine targets.
For more information on Dr Kis’ work, read https://www.sheffield.ac.uk/news/vaccine-development-and-mass-production-set-be-accelerated-new-manufacturing-unit.