While research on mRNA vaccines has been ongoing for years, the advent of the recent SARS-CoV2 pandemic expedited this research to clinical approval, such that large portions of our population have been inoculated with an mRNA vaccine (e.g. Pfizer and BioNTech’s BNT162b2 and Moderna’s mRNA-1273). These vaccines are proving to be a breakthrough form of immunization with wide and far-ranging applications.
Before we get into what makes mRNA vaccines the breakthrough that they are, let’s take a quick refresher at immunization and how vaccines typically work. When exposed to a foreign antigen, the human body will mount an immune response, releasing white blood cells that attack and eradicate the invading molecule. The immune system then creates “memory cells” that recognize the same pathogen,, for a faster immune response the next time around. A vaccination takes advantage of the memory in the immune system by:
deliberately exposing the human body to a dead or deactivated pathogen to induce an immune response so that
subsequent immune responses can be quicker and more specific.
So what does this have to do with mRNA vaccines?
mRNA vaccines work in a nearly identical way to regular vaccines, except they contain the blueprint for a pathogen protein — — i.e, the mRNA — — rather than the protein or a deactivated pathogen, as in regular vaccines. Once injected, the mRNA is transcribed into the protein by harnessing the machinery of cells in the human body.
One advantage of mRNA vaccines is safety: mRNAs, unlike their protein or attenuated pathogen counterparts, are inherently inert, and so the risk of infection is much lower. Another advantage is that they can be manufactured at scale more easily. [Nature]
But what took so long for these vaccines to get approval?
It’s a common joke in biochemistry circles, that if you look at mRNA the wrong way it’ll denature. On its own, mRNA doesn’t stay stable too long and will denature (akin to decomposing or dissolving), and so while a seemingly simple answer to our immunization needs, mRNAs instability has always been an issue. The first time an mRNA vaccine was prepared was back in the 1980s, and there have been several million dollar attempts by large pharmaceutical companies to encourage the development of stable mRNA vaccines [Nature]. However, there was never any success in being able to create some form of packaging that would keep the mRNA stable through storage, vaccination and entry into human cells; that is until the current pandemic which became an impetus behind the research of mRNA vaccines and their packaging — showing that liquid nanoparticles proved to be an ideal vector for delivering mRNA into the human body intact.
With these discoveries the sky’s the limit for the various applications of mRNA vaccines, especially when looking at treating certain cancers, but that’s a story for another day.