Pfizer-BioNTech are making a mRNA vaccine, but what is that?

Covid-19 blog for the non-expert

Screenshot 2020-11-12 at 14.27.24The Pfizer-BioNTech vaccine for Covid-19 is all over the media. What hasn’t been in the headlines so much, is that this is a mRNA vaccine and if successful, it’ll be the first of its type. Some say they will not take it because it’s “rushed” but this misses the point that we are not making vaccines in the same way we did even a few years ago, and in fact mRNA vaccines have been in development for over three decades.

But what is a mRNA vaccine and why are they so important? In this blog post I try to explain.

The general principle behind a vaccine is that it contains something called an antigen – a piece of the target pathogen (or something resembling the pathogen) that the body recognises as being foreign. The antigen is such that it’s able to trigger an immune response, but without causing the disease itself. In a way, it fools the immune system an infection has occurred, thus sounding the bugle for attack. The attack in the case of the immune system is to produce antibodies that latch onto the antigen acting as beacons to white blood cells (called T-cells) which come along and destroy the pathogen. Key to vaccination is the fact that the immune system bares a grudge even bigger than in a Mafia war. The immune system, like the Corleone family, “goes to the mattresses” and patiently waits. If the antigen, this time in the form of the genuine pathogen, should reappear, then the immune system comes out of hiding and attacks before the disease has had a chance to fire a shot.

To understand how a mRNA vaccine brings the immune system into play against a pathogen, we first need a little biochemistry. As I’m sure you know, DNA contains a code in the form of base-pairs which our biochemistry translates into proteins. There is however, an intermediate step whereby the code in DNA is first translated and carried to the protein-making mechanisms within cells by messenger-RNA (mRNA). This is happening inside the cells of your body all the time, making new protein from enzymes to muscle to haemoglobin. A mRNA vaccine works on the principle that part of the viral DNA (or RNA in the case of SARS-CoV-2) is translated to mRNA in the laboratory. Following modification, this mRNA gets placed into a lipid nanoparticle. Before any Bill Gates conspiracy theorists get too excited, the lipid nanoparticle isn’t a microchip, it’s simply a lipid (fat) particle about a billionth of a meter in diameter (hence “nano”) that helps the mRNA cross biological membranes to enter cells. Once in the cell, the protein-making machinery translates mRNA into the viral antigen. In many ways, this is similar to what the virus does when it takes over a cell to make more copies of itself – biotherapeutic irony perhaps. Once the viral antigen is present, then the immune system triggers in the same way I’ve described above. It sounds simple, but there are complexities. The viral antigen, made from mRNA, is part of the spike protein on SARS-CoV-2, which latches onto the human cell to gain entry. It’s important to select mRNA for an appropriate part of the spike protein because the cunning virus coats much of it in sugar molecules to hide it from antibodies. Biochemistry is never that straightforward.

The likely starting point for mRNA vaccines appears to be 1989 when a San Diego biotech company called Viral Inc published the first paper*. In the early days, it was all done in test tubes (in vitro) or with animal models and the first human trials took place in the early 2000s. Despite some efforts, a successful mRNA vaccine has eluded researchers up until now, and so if the Pfizer-BioNTech vaccine is successful, it will be first in its class. Of course, no therapy is entirely risk free and some side effects have been reported over the years, but I’ll leave this to another time, if the vaccine gets approval. I should add however, that in respect to the current Covid-19 clinical trials with over 43,000 participants, the vaccine does look very safe.  The other issue with this type of vaccine, which the media has widely publicised, is the need for storage at -70℃ because of the inherently unstable nature of mRNA. That, however, is a logistical question and so I’ll not tackle that one here. Personally, I would say there’s some benefit in a more gradual roll-out, if for nothing else to allay the fears of some of the public on its safety. (However, -70℃ storage does cause problems in the developing world).

If this does turn out to be the first mRNA vaccine the implications are indeed profound. This is what’s known in the biotech industry jargon as a platform technology. As time goes on and we acquire more experience, then its perfectly possible a mRNA vaccine could be made within a few months to combat future pandemics – which will surely come sooner or later (let’s hope later). In fact, it’s not necessary to even isolate the virus in order to make the vaccine, it can be done from just knowing the sequence of the genetic code, which is routine these days. In the case of SARS-COV-2, the disease (Covid-19) was first reported in December 2019, and by February 2020 the 26,000 – 32,000 RNA code sequence went round the world via the internet. The rate limiting step therefore, will likely not be the vaccine itself but the safety tests and clinical trials.

And finally a note of extra optimism. If Pfizer-BioNTech stalls then other vaccines are coming through apace and I suspect announcements will appear soon. Some of these will be other mRNA vaccines and others will be vector types. And, as some have asked, would I take it? You bet – I’d be first in line if I could be.

We have likened the pandemic to wartime and in many ways that analogy holds true, because it’s times of the greatest threat to humankind that we seem to make our most profound advances.

* R.W. Malone, P.L. Felgner, I.M. Verma, Proc. Natl. Acad. Sci. U.S.A., 86 (1989), pp. 6077-6081. 

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