Weekend Long Reads: mRNA Vaccines

by Kevin Schofield

This week's "long read" is an article in the journal Nature, looking at the long and complicated path leading to the mRNA vaccine technology and techniques used to create the Moderna and Pfizer vaccines against COVID-19.

"Messenger RNA," or mRNA, is essentially a recipe for building proteins. Living cells use it as a way of passing notes around: Parts of our DNA are transcribed into mRNA, which is then read by the tiny factories in our cells that produce proteins.

Technically, a virus isn't alive: It's just a string of genetic material surrounded by a coating of fat (what biologists call "lipids") with some proteins on the surface that help it to gain access into our cells (such as the COVID-19 "spike protein"). Once a virus invades our cells, its DNA is also transcribed into mRNA that contains the blueprint for the virus, and then our own cells do all the hard work to churn out thousands of virus copies.

The earliest vaccines were "dead" versions of the virus they were intended to protect against: They get into our bloodstream where our immune system learns to recognize and attack them. Later generations of vaccines have been various forms of "live": either a weakened version of the virus that can still invade and potentially reproduce to better stimulate our immune systems but can't make us sick, or a different but harmless virus with a small part of the harmful one grafted on so our immune system learns to recognize it.

But the COVID-19 mRNA vaccines work differently. There is simply a chunk of messenger RNA, wrapped up in a bubble of lipids similar to a virus's packaging. But once inside our cells, the vaccine's mRNA instructs our cells to make copies of the COVID-19 spike protein — only the spike protein, not the rest of the virus — to train our immune system to recognize and attack it.

Scientists have been using mRNA to explore and understand cell function since the 1960s. But it took until the mid-1980s before they invented a method for synthesizing it. That led to the idea, first proposed in 1987, that we could "treat RNA as a drug" by injecting it into the body. But realizing that notion was far from simple: mRNA is a delicate, unstable medium that is difficult to work with. Over the following decades, researchers had to devise a new form of lipid bubble that would attach and envelop mRNA to protect it, both in storage and as it made its way into our bodies. They also had to find a way to stop our immune systems from deciding that the mRNA was an invader and attacking it before it could get into our cells.

But by the beginning of 2020, all of the pieces were in place, and when COVID-19 appeared, the leading companies were poised to jump. Literally within days of having the virus genetically sequenced in January, scientists at Moderna and Pfizer/BioNTech had designed mRNA vaccines coded to COVID-19's spike protein and were ready to start early-stage testing.

It was the first major success for mRNA vaccines, pointing to a bright future for the technique to quickly create vaccines for emerging infectious diseases — not to mention other diseases such as influenza and even potentially some cancers. But who gets the credit, when the outcome can be traced back to a collection of critical advances over several decades?

The Nobel Prize Committee is apparently pondering that question now, and many pioneers who made contributions along the way are wondering whether they will be recognized — or snubbed.

The Tangled History of mRNA Vaccines

Featured image is attributed to Prachatai (under a Creative Commons, CC BY-NC-ND 2.0 license).