mRNA vaccine pioneers win Nobel Prize

 

Two US-based scientists were awarded this year’s Nobel Prize in Physiology or Medicine for their work in pioneering key discoveries that enabled the success of mRNA vaccines that were widely deployed against the Covid-19 pandemic.

They are the Hungarian-born biochemist Katalin Karikó and the US-born immunologist Dr Drew Weissman, who were colleagues at the University of Pennsylvania when they published their seminal paper in 2005.

In its press release, the Nobel Assembly at Karolinska Institutet said studies on producing mRNA without using cell culture for therapeutic purposes began in the 1980s but hit several obstacles.

These in vitro mRNA proved unstable, were difficult to deliver, and produced an inflammatory response in recipients.

By studying how different types of mRNA interact with the immune system, however, the duo found a way to modify the in vitro mRNA such that it does not provoke an inflammatory response.

“Karikó and Weissman knew that bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not.

“They wondered if the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction.

“To investigate this, they produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells.

“The results were striking: The inflammatory response was almost abolished when base modifications were included in the mRNA. This was a paradigm change in our understanding of how cells recognise and respond to different forms of mRNA.

“Karikó and Weissman immediately understood that their discovery had profound significance for using mRNA as therapy,” it said.

Clinical applications of mRNA

In follow-up studies published in 2008 and 2010, the Nobel Assembly said the duo showed the modified mRNA also had markedly increased protein production compared to unmodified mRNA.

“Through their discoveries that base modifications both reduced inflammatory responses and increased protein production, Karikó and Weissman eliminated critical obstacles on the way to clinical applications of mRNA,” it said.

After 2010, several companies developed the method for potential use against the Zika virus and MERS-CoV. The latter is closely related to the SARS-CoV-2 virus that emerged in 2019 causing the Covid-19 pandemic.

mRNA vaccines against Covid-19 - developed by Pfizer with BioNTech, as well as by Moderna - are among the most widely used vaccines against the pandemic. Compared to other vaccine technologies, they also proved more easily adapted against new variants of the virus.

In Malaysia alone, Health Ministry (MOH) data shows that as of Sept 30, 62 percent of the 7.2 million Covid-19 vaccine doses administered in the country is the Pfizer-BioNTech vaccine. The Moderna vaccine is not available in Malaysia despite receiving MOH approval.

“The impressive flexibility and speed with which mRNA vaccines can be developed paved the way for using the new platform also for vaccines against other infectious diseases.

“In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types,” the Nobel Assembly said. - Mkini