Nobel Prize 2023: Katalin Kariko, Drew Weissman awarded for work that led to effective mRNA vaccines against COVID-19

Nobel Prize 2023: Katalin Kariko, Drew Weissman awarded for work that led to effective mRNA vaccines against COVID-19

Subject: Science and Technology

Section: Biotechnology

Context:

• The 2023 Nobel Prize for Medicine has been jointly awarded to United States scientists Katalin Kariko and Drew Weissman for their work concerning “nucleoside base modifications that enabled the development of effective messenger ribonucleic acid (mRNA) vaccines against COVID-19”.

About their contribution in vaccine development:

• The discoveries and findings by Kariko and Weissman fundamentally changed the understanding of how mRNA interacts with the human immune system.
• This contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.

From the dawn of vaccination till recently, vaccines have been made from:

• Killed or weakened viruses.
• Parts of the viral genetic code, usually encoding proteins found on the virus surface, used to make proteins that stimulate the formation of virus-blocking antibodies.
• Parts of the viral genetic code moved to a harmless carrier virus or ‘vector’.

What are mRNA vaccines and how do they work?

• All vaccines introduced into the body a harmless piece of a particular bacteria or virus, triggering an immune response. Most vaccines contain a weakened or dead bacteria or virus.
• However, scientists have developed a new type of vaccine that uses a molecule called messenger RNA (mRNA) rather than part of an actual bacteria or virus. Messenger RNA is a type of RNA that is necessary for protein production. Once cells finish making a protein, they quickly break down the mRNA. mRNA from vaccines does not enter the nucleus and does not alter DNA.
• mRNA vaccines work by introducing a piece of mRNA that corresponds to a viral protein, usually a small piece of a protein found on the virus’s outer membrane. (Individuals who get an mRNA vaccine are not exposed to the virus, nor can they become infected with the virus by the vaccine.)
• By using this mRNA, cells can produce the viral protein. As part of a normal immune response, the immune system recognizes that the protein is foreign and produces specialized proteins called antibodies.
• Antibodies help protect the body against infection by recognizing individual viruses or other pathogens, attaching to them, and marking the pathogens for destruction. Once produced, antibodies remain in the body, even after the body has rid itself of the pathogen, so that the immune system can quickly respond if exposed again.
• If a person is exposed to a virus after receiving mRNA vaccination for it, antibodies can quickly recognize it, attach to it, and mark it for destruction before it can cause serious illness.

Need for mRNA based vaccines and challenges in developing them:

• Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture, which limits the possibilities for rapid vaccine production in response to outbreaks and pandemics.
  • Genetic information encoded in human DNA is transferred to messenger RNA (mRNA) in the body’s cells and is used as a template for protein production.
• Scientists were able to produce mRNA without cell culture in the 1980s, in a process known as in vitro transcription. But there are two challenges associated with it:

1. In vitro transcribed mRNA was considered unstable and challenging to deliver, requiring the development of sophisticated carrier lipid systems to encapsulate the mRNA.
2. In vitro-produced mRNA gave rise to inflammatory reactions.

How Kariko and Weissman improved the mRNA vaccine technology?

• Kariko and Weissman noticed that dendritic cells (which have important functions in immune surveillance and the activation of vaccine-induced immune responses) recognize in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules.
• Theywanted to test a hypothesis as to whether the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction.
  • RNA contains four bases, abbreviated A, U, G, and C, corresponding to A, T, G, and C in DNA, the letters of the genetic code.
• They produced different variants of mRNA, each with unique chemical alterations in their bases, when they delivered it to dendritic cells the found that:
  • Inflammatory response was almost abolished when base modifications were included in the mRNA. And,
  • It markedly increased protein production compared to unmodified mRNA.
• After the outbreak of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed.
• Such vaccines have resulted in saving millions of lives and prevented severe disease in many more, allowing societies to open and return to normal conditions.

About the Nobel Prize:

• The Nobel Prizes are five separate prizes (Physics, Chemistry, Physiology or Medicine, Literature, and Peace) that, according to Alfred Nobel’s will of 1895, are awarded to “those who, during the preceding year, have conferred the greatest benefit to humankind.”
  • Nobel characterized the Peace Prize as “to the person who has done the most or best to advance fellowship among nations, the abolition or reduction of standing armies, and the establishment and promotion of peace congresses”.
• In 1968, SverigesRiksbank(Sweden’s central bank) funded the establishment of the Prize in Economic Sciences in Memory of Alfred Nobel, to also be administered by the Nobel Foundation.
• The prize ceremonies take place annually at Stockholm, Sweden, while the Nobel Peace Prize is awarded in Oslo, Norway.
• Each recipient (known as a “laureate”) receives a green gold medal plated with 24 karat gold, a diploma, and a monetary award.
• In 2021, the Nobel Prize monetary award was 10,000,000 SEK. In 2023, the monetary award is set to increase to 11,000,000 SEK.
• A prize may not be shared among more than three individuals, although the Nobel Peace Prize can be awarded to organizations of more than three people.
• Although Nobel Prizes are not awarded posthumously, if a person is awarded a prize and dies before receiving it, the prize is presented.
• The Nobel Prizes, beginning in 1901, and the Nobel Memorial Prize in Economic Sciences, beginning in 1969, have been awarded 609 times to 975 people and 25 organisations.
• Five individuals and two organisations have received more than one Nobel Prize.