In a historic announcement, the Nobel Prize in Physiology or Medicine for 2023 has been awarded to biochemist Katalin Karikó and Drew Weissman, recognizing their groundbreaking contributions to mRNA research. Their work laid the foundation for what has become one of the most influential medical advancements of our time: the development of mRNA vaccines against COVID-19.

Karikó, currently at the University of Szeged in Hungary, and Weissman from the University of Pennsylvania, received this prestigious honor for their pioneering research on modifying mRNA. These modifications were crucial in making the first COVID-19 vaccines possible, notably those produced by Pfizer/BioNTech and Moderna.

Revolutionizing Vaccines

Traditional vaccines typically use weakened or killed viruses, bacteria, or proteins from pathogens to stimulate the immune system. However, mRNA vaccines work differently. They contain genetic instructions for building viral proteins. When administered, these instructions prompt cells to temporarily produce the viral protein, triggering an immune response. The immune system then builds defenses, providing protection if the person is later exposed to the actual virus. This may sound familiar, as AP Bio has taught about immune response and cells. We learned that memory T cells are a crucial component of the immune system, formed after the body encounters a pathogen like a virus or bacteria. These specialized cells “remember” the specific characteristics of the invader, allowing for a rapid and targeted response upon subsequent exposures, effectively combating and neutralizing the illness. Memory B cells, a crucial component of the adaptive immune system, exhibit remarkable specificity and functionality. During the primary immune response, these cells undergo affinity maturation, producing high-affinity antibodies with increased binding capacity to pathogen-specific antigens. Notably long-lived, memory B cells persist in the body, ensuring prolonged immunity. Upon re-exposure, they swiftly differentiate into Plasma B cells, which serve as antibody factories, producing copious amounts of antibodies tailored to the familiar pathogen. On the other hand, memory T cells, including cytotoxic and helper T cells, play distinct yet coordinated roles. Cytotoxic T cells retain the capacity to directly eliminate infected cells, preventing pathogen spread, while helper T cells release cytokines that stimulate antibody production by B cells and enhance cytotoxic T cell activity. With immunological memory, memory T cells provide rapid and targeted responses upon reinfection, actively surveilling for cells displaying specific antigens associated with previously encountered pathogens. Together, these memory cells form a sophisticated and enduring defense mechanism, contributing to the immune system’s ability to combat and neutralize pathogens efficiently.

The technology behind mRNA vaccines has proven immensely effective in combating the COVID-19 pandemic. As of September 2023, over 13.5 billion COVID-19 vaccine doses, including mRNA vaccines and other types, have been administered globally. These vaccines are estimated to have saved nearly 20 million lives worldwide in the year following their introduction.

Modified mRNA and Its Potential

RNA, the lesser-known cousin of DNA, serves as the genetic instruction manual for cells. Messenger RNA (mRNA) copies genetic instructions from DNA and is crucial for protein synthesis. Karikó and Weissman’s pivotal contribution was modifying mRNA building blocks to overcome challenges in early trials.

Traditional mRNA injection would trigger adverse immune reactions, leading to inflammation. By swapping the RNA building block uridine for modified versions, the researchers found a solution. Pseudouridine and later N1-methylpseudouridine proved effective in dampening harmful immune responses. This breakthrough, dating back to 2005, enabled the safe delivery of mRNA to cells.

“The messenger RNA has to hide and go unnoticed by our bodies,” explains Kizzmekia Corbett-Helaire, a viral immunologist at the Harvard T. H. Chan School of Public Health. The modifications developed by Karikó and Weissman were fundamental, allowing mRNA therapeutics to hide while being beneficial to the body.

This technology extends beyond COVID-19, with potential applications against other infectious diseases, cancer, and even rare genetic disorders. Clinical trials are underway for these applications, though results may take several years to emerge.

A Journey Decades in the Making

The road to this groundbreaking achievement was not without obstacles. In 1997, Karikó and Weissman, working in separate buildings, collaborated to address a fundamental problem that could have derailed mRNA vaccines. Initial setbacks, including failed clinical trials in the early 90’s, led many researchers to abandon mRNA as a viable therapeutic approach.

Undeterred, Karikó and Weissman persisted. “We would sit together in 1997 and talk about all the things that we thought RNA could do,” Weissman reflected. The duo’s resilience led to the formation of RNARx in 2006, a company dedicated to developing mRNA-based treatments and vaccines.

Despite the groundbreaking nature of their work, Karikó’s contributions were initially overlooked. Ten years ago, she faced termination from her job and had to move to Germany without her family to secure another position. The Nobel recognition sheds light on her unwavering commitment to mRNA therapeutics.

The Nobel Committee’s decision to acknowledge this achievement swiftly, a mere three years after the vaccines demonstrated their medical importance, highlights the urgency and impact of mRNA technology. Emmanuelle Charpentier and Jennifer Doudna’s Nobel Prize for Chemistry in 2020, awarded eight years after the description of CRISPR/Cas 9, reflects a similar trend of more current acknowledgments.

In a press conference at the University of Pennsylvania, Weissman expressed his surprise at the recognition. “I never expected in my entire life to get the Nobel Prize,” he confessed. The laureates will share the prize of 11 million Swedish kronor, approximately $1 million.

A Nobel-Worthy Legacy and a Glimpse into the Future

The timely recognition of Katalin Karikó and Drew Weissman emphasizes the transformative potential of mRNA therapeutics, extending far beyond the current success against COVID-19. As we celebrate this Nobel-worthy legacy, it opens a new chapter in medical science, offering hope for innovative solutions to combat various diseases and improve human health.

The journey from a meeting in 1997 to the global impact of mRNA vaccines in 2023 showcases the power of perseverance, collaboration, and the pursuit of groundbreaking ideas. 

What do you think about mRNA vaccines? Did/Will you receive one?

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