France has just launched a new vaccination campaign against Covid-19 that caused the pandemic that began in 2020. The same thing happens in the USA and other countries of Europe, where hospitalizations, admissions to intensive care units and, in some cases, deaths increase.
But the truth is that the pandemicwithout the S vaccines that were developed, tested in clinical trials, produced, approved and distributed in Record time (less than a year) would have been very different. Only between December 8, 2020 (when the first vaccine was administered outside of a clinical trial setting) and the same date in 2021 is it estimated that Vaccines prevented 19.9 million deaths from Covid-19 in the world. That is, a 63 percent reduction.
It is true that there were and are vaccines developed and produced from different platforms, and one of them is the one that was awarded the Nobel Prize in Medicine and Physiology announced the first week of October. The assembly of Karolinska Institute that is formed each year decided to grant the 2023 recognition to Katalin Karikó and Drew Weissman for his discoveries on nucleoside base modifications that allowed the development of effective mRNA vaccines against the SARS-CoV-2 coronavirus.
“Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the awardees helped achieve vaccine development at an unprecedented pace, during one of the greatest threats to human health in the modern era”, summary from Karolinska.
Katalin Karikó was born in 1955 in Szolnok, Hungary. She studied and received her doctorate in her home country and conducted postdoctoral research at Temple University, Philadelphia and Health Science University, Bethesda (in the United States). Several years later she became vice president and then senior vice president of BioNTech RNA Pharmaceuticalsthe company that (together with the pharmaceutical company Pfizer) developed the first vaccine against Covid-19.
For his part, Drew Weissman was born in 1959 in the United States and received his medical degree and doctorate from Boston University. In 1997, Weissman established his research group at the Perelman School of Medicine at the University of Pennsylvania. He is director of the Penn Institute for RNA Innovations.
Long term technologies
Vaccination stimulates the formation of an immune response to a particular pathogen. This gives the body an advantage in fighting disease in the event of subsequent exposure. Vaccines based on killed or weakened viruses have long been available, such as vaccines against polio, measles and yellow fever. In 1951, Max Theiler received the Nobel Prize in Physiology or Medicine for developing the yellow fever vaccine.
Based on advances in molecular biology in recent decades, specialists have developed vaccines based on individual viral components, instead of complete viruses. Parts of the viral genetic code, which normally encode proteins found on the surface of the pathogen, are used to produce proteins that stimulate the formation of antibodies that block the virus. This is the case of vaccines against hepatitis B virus and human papillomavirus.
It is also feasible to transfer parts of the viral genetic code into a harmless carrier virus, a “vector.” This method is used in vaccines against the Ebola virus. When vector vaccines are injected, the selected viral protein is produced in the body’s cells, stimulating an immune response against the target virus.
The production of vaccines based on whole viruses, proteins and vectors requires large-scale cell culture, which limits the possibility of having vaccines produced quickly, as required in a pandemic. One option was to develop vaccine technologies that were independent of cell culture. Something that was not easy to achieve.
The fast and complex method
What does the development of Karikó and Weissman consist of? The genetic information encoded in the DNA of cells is transferred to messenger RNA (mRNA), which is used as a template for the production of proteins. Efficient methods for producing mRNA without cell culture, called in vitro transcription, were introduced during the 1980s. However, the method was considered unstable and problematic by experts. Furthermore, mRNA produced in vitro gave rise to inflammatory reactions. Enthusiasm for developing mRNA technology for clinical purposes froze.
However, Katalin Karikó and Drew Weissman began working together on the technology, investigating how different types of RNA interact with the immune system. Arikó had already been focusing on mRNA, and Weissman was looking for new approaches to developing an HIV vaccine. And they started working together. They observed that certain cells (dendritic cells) recognize the mRNA transcribed in vitro as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules. The immune system interprets the mRNA as an invading pathogen and attacks it, making the animals sick while destroying the mRNA.
However, over time, both researchers found that this did not happen in the case of mRNA from mammalian cells. That is, there are different types of mRNA with particular properties.
To investigate them, Karikó and Waissman produced different mRNA variants, each with unique chemical alterations. Until they found a way to almost nullify the inflammatory response. The discovery was published in 2005, with new data in 2008 and 2010: the provision of modified mRNA markedly increased protein production compared to unmodified mRNA.
Closer to vaccines
Interest in mRNA technology began to increase and, in 2010, several scientific teams sought to manufacture vaccines against the Zika virus and MERS-CoV; the latter is closely related to SARS-CoV-2.
During the pandemic, two mRNA vaccines with modified nucleoside bases encoding the surface protein of SARS-CoV-2 were developed at a record pace. Protective effects of around 95% were reported and both vaccines were approved as early as December 2020.
“The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccines against other infectious diseases,” the members of the Nobel Committee point out. In the future, the technology could also be used to deliver therapeutic proteins and treat some types of cancer.
Several other vaccines against SARS-CoV-2 were also tested, based on different methodologies. They were introduced quickly and together more than 13 billion Covid-19 vaccine doses have been administered worldwide. Vaccines saved, once again, millions of lives and continue to prevent progression to serious symptoms of the disease. Vaccines helped people’s activities, economic production, entertainment, social relationships, and travel, little by little return to normal conditions.
But in addition, the work of the Nobel Prize winners in Medicine laid the foundations for vaccines that could one day protect against various deadly diseases. Vaccines using mRNA technology against influenza, malaria and HIV are currently being developed. Personalized cancer vaccines have also shown promise. They use mRNA tailored to an individual patient’s tumor to teach the person’s immune system to attack tumor proteins.
Difficulties and struggle
Karikó is also the thirteenth woman to win the Nobel Prize in Medicine, the first since 2015. She did not have a good time, her research remained in the shadows for many years without funding and she did not have a permanent academic position. In fact, she was forced to withdraw from college a decade ago.
Waissman didn’t have a good time either: the first major paper (scientific document) he wrote with Kerikó in 2005 was rejected by the magazines Nature and Science. It was later accepted by the specialized publication Immunity.
Even when biotechnology companies Moderna (American) and BioNTech (German) became interested in the platform to develop vaccines, there were still problems: they investigated the use of mRNA vaccines for influenza and cytomegalovirus, among other diseases. They never got out of the primary stage of clinical trials.
The SARS-CoV-2 coronavirus and the Covid-19 pandemic, which left at least seven million dead in the world, changed everything.
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