COVID vaccine: is it safe?

How does an RNA vaccine work, and what are the risks?
17 December 2020

Interview with 

Chris Smith, the Naked Scientists


A vaccination.


The first authorised vaccine for the coronavirus has begun its rollout. Produced by companies Pfizer and BioNTech, it’s what’s known as an mRNA vaccine, just like another one that has passed phase 3 clinical trials: Moderna’s. With other countries close behind, we can expect many hundreds of thousands of people to have received it before 2020 is out. But a sizeable number are nervous about getting the jab. So Phil Sansom asked virologist and Naked Scientist Chris Smith to explain what an mRNA vaccine actually is…

Chris - RNA is a chemical relative of DNA; so it's a form of genetic information. And in our bodies, it is used to carry a copy of the gene that you want to use, out to the part of the cell that can decode that gene and turn it into a protein; something the cell can actually do something with. So it's a short-lived message that moves something from a gene to becoming a protein. But some forms of life, and specifically some viruses, rather than using DNA like we do, they use this form of genetic material - RNA - as their main information storage mechanism.

Phil - What RNA message then is this vaccine RNA carrying?

Chris - What they've done is to go to the virus genetic code and find the piece of that code that corresponds to the outer coat of the virus, and specifically a structure called the S protein, or spike - S for spike - protein. They've taken just that short piece of the RNA from the virus, and they've put that into a package, so it's effectively wrapped up in an oily coat. So when injected, it's picked up by cells, unwrapped; and because cells understand genetic material like that piece of RNA, they can decode the recipe on there and make the protein that it would have made if the virus was in the cell for real, and then display that protein to the immune system, showing the immune system what a cell that would be infected with coronavirus would make.

Phil - What happens to the little bits of RNA? Where do they go?

Chris - The thing about RNA is that it is a very transitory thing. It has a really short lifetime in cells, and it very quickly is degraded. There are mechanisms there whose job it is to eat it and break it apart. So when you put the vaccine mRNA into the cell, it too is terminated very quickly, which is why you need to have a big dose of the vaccine; and not just once, but twice.

Phil - Now am I right this is the first time that this tactic's really been used?

Chris - People have made genetic vaccines in the past, but they've never used them in humans. They've been used, tested and deployed successfully in animals - most recently actually for Zika virus - but this had not been done in humans. And so now the know-how from those earlier experiments which we've been learning about for a couple of decades, actually, have now for the first time been successfully deployed in humans to combat coronavirus.

Phil - What are the risks here? Because you'd expect any medical treatment come with inbuilt risks or side effects.

Chris - The risks range from the very trivial to the more serious. At the very trivial end of the spectrum, all medicines have side effects. This vaccine series is no exception. Those side effects usually are things like pain at the injection site; you're sticking a needle into somebody, it will be a bit uncomfortable. Slightly more serious: a handful of people might get some trivial side effects. By 'trivial' we mean things like: you might feel a bit fluey for a day or so. This is actually to be expected; it's because the immune system is responding to what's come into the body - that's the whole point of doing this after all - and when you have an immune response you produce various immune signals, and you feel unwell for a day or so, because that is the process that's happening when the immune system is being stimulated. The more severe end of the spectrum: very, very rarely, with some medicines you get what are called idiosyncratic reactions; and this is where, because every single person on earth, unless you have a twin or you've cloned yourself... everybody's genetically distinct, therefore they're biochemically distinct on the inside. And as a consequence of that, there is a small chance that in a very rare circumstances, some people may just overreact to some medicine or react in an unpredictable way. It's very, very rare; this is what clinical trials are designed to screen out; and so you don't license things that you think there's an appreciable chance of this happening.

Phil - What if you have some sort of autoimmune condition? Does that make a difference?

Chris - Autoimmune conditions are where the immune system attacks your own tissues. And there are lots of control mechanisms in place to stop the power of the immune system being turned on you, because it can be very destructive. The reason that this may be a problem with vaccination is that when we have a case of an autoimmune disease, it's controlled by suppressing the immune system with various drugs. These are a bit of a blunderbuss thing; they turn down all of the immune system. So when you do give people vaccines, they might not make the same robust, resilient immune response that someone would make were they to have a normally functioning immune system. It's not a given that they won't, but it's a possibility that they won't respond as well as someone with a healthy immune system. So it can be a consideration. Also, if people have an immune system that doesn't quite work properly for a range of reasons - there are inherited reasons, there are some acquired reasons, some diseases that could do this - they may overreact to certain things. But those sorts of situations are very rare.

Phil - Some people are sort of understandably hesitant, because they see a vaccine that's been developed, to anyone's eyes, remarkably quickly. Is it possible that there are unknown unknowns here?

Chris - There are always unknown unknowns in everything that we do. And unfortunately, inherent to everything there is some degree of risk, and that's a fact of life. And there is no way of getting around that. But what you do have to do is to take the greatest steps that you can to minimise that risk, to the greatest extent that you can. And that has been done here. Because what they have done is to take decades of learning about vaccines, and about actually making vaccines the way that these ones have been made; you then do trials on people to test the safety of them; you then put in place post marketing trials, so follow-up trials, so that you follow the people and you have a system in place to look for adverse outcomes. And at the same time, the approvals process has been streamlined for this new vaccine. Now what that means is to have a two way conversation between the drug manufacturers and developers, and the regulators, all the time, so that many of these things have been speeded up enormously so that there are no delays. What they haven't done is to cut the corners in the scrutiny, and they certainly haven't lowered the threshold for what that they'll accept as safe, because number one on the list is 'safe'. What we can never know is what the long term effect is. We don't have a time machine or a crystal ball; you can't see into the future. So the question we'd most like answered is: how long will I remain immune for? And we have no idea. But what we do know is: we're going to find out, and we'll find out by following up the people that get vaccinated.


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