mRNA vaccine pioneers recognised with Nobel Prize

The Nobel Prize in Medicine has been awarded to a pair of scientists whose research led to the development of vaccine technology widely used in response to COVID-19.

Hungarian biochemist Katalin Karikó and American immunologist Drew Weissman were recognised by the Nobel Assembly for their work enabling the development of messenger RNA (mRNA) vaccines for use during the recent COVID-19 pandemic.

Those vaccines are groundbreaking in terms of the relative simplicity and speed of development and deployment. In a statement, the Nobel Assembly described the new laureates’ research as “critical for developing effective mRNA vaccines against COVID-19”.

“Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”

Karikó and Weissman have been colleagues at the University of Pennsylvania since the 1990s when their collaborations into synthetic mRNA technology and human immune responses began. Their breakthrough determined that lab-produced mRNAs were treated as foreign entities by the immune system. Further experiments found natural chemical modifications to the body’s own mRNA avoided inflammatory response, explaining why unmodified lab versions of mRNA code led to immune reactions.

Work published by the pair and their collaborators in 2005, 2008 and 2010 “eliminated critical obstacles” towards clinical applications of mRNA technology, according to the Nobel Assembly.

Faster – and safe – vaccine tech

Vaccines trigger an immune response to a pathogen, and traditional preparations have typically done so by exposing the human body to a live or killed virus. Live viruses are delivered in weakened or ‘attenuated’ states and have been widely used to provide immunity to many diseases.

Such technology led to the awarding of the 1951 prize for medicine to Max Thieler for his work developing an attenuated yellow fever vaccine.

In recent decades, vaccine development has shifted towards triggering antibody responses to specific viral parts, such as its surface proteins or via harmless viral vectors. Traditional vaccine technology and testing for human use had typically been a time-consuming process, but the emergence of mRNA technology over the last three decades has provided an avenue to speed up vaccine development.

mRNA is essential in the functioning of the human body as a transcription tool. While DNA is home to the genetic code of organisms like humans, mRNA performs the role of ‘reading’ the code. This mRNA contains a template for transcribing specific genes into vital proteins that allow organisms to grow and function.

The principle applies to mRNA vaccines, which possess a segment of lab-made mRNA that typically corresponds to the genetic code for the pathogen’s surface proteins. Once the vaccine is received, the recipient’s body identifies the piece of mRNA and creates a protein identical to the surface receptor of the real virus: in the case of COVID-19 vaccines, the surface ‘spike’ protein doesn’t carry the pathogenic code of the whole virus, it’s merely the target the immune system learns to attack.

In effect, the body is enabled to train itself against a ‘blank’ target, producing an immune response and specialised lymphocyte white blood cells capable of identifying the real thing if a person becomes infected.

While an adenovirus ‘vector’ vaccine produced by Oxford and AstraZeneca was the first deployed for human use early in the pandemic, many people around the world were offered mRNA vaccines developed by companies like Pfizer and Moderna as their first jab.

Pandemic marks the first at-scale use of mRNA vaccines

In its statement, the Nobel Assembly described the use of mRNA vaccines addressing the COVID-19 pandemic as “transformative”.

While mRNA vaccines had been developed against other diseases like Zika virus and the COVID-like MERS-CoV, the recent pandemic provided an avenue for the Pfizer and Moderna vaccines to be developed and deployed at scale.

“The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform for vaccines against other infectious diseases. In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types,” says the Nobel Assembly.

Professor Paul Griffin, a clinical microbiologist who heads the Mater Hospital Clinical Unit in Queensland, described Karikó and Weissman as worthy recipients of the Nobel Prize and emblematic of the strides vaccine research has taken over 30 years.

“[The award] is an indicator of the magnitude of the discovery and just how tremendous it’s been, but also the amount of work that has gone into it,” Griffin tells Cosmos.

Griffin was a frequent go-to health commentator during the pandemic in Australia, but says elevating the pioneering research that originated with Karikó and Weissman shows the long build-up of research that goes into the development of groundbreaking medical technology.

“Hearing the story of what’s gone into this, and it’s been 30+ years in the making: mRNA vaccines were not just something that was dreamed up just before the pandemic, it’s something that has a very robust scientific basis from some tremendous scientists that continued to develop it despite facing a lot of adversity.

“It’s made such a big difference during the pandemic and will for a whole host of other pathogens as well.”