How would a COVID-19 vaccine work?

Why is it so hard to make a coronavirus vaccine?
02 June 2020

Interview with 

Gordon Dougan, University of Cambridge


Ampoules and vials of vaccine


Dozens of labs around the world are all working hard to make a vaccine for COVID-19. But what would that vaccine look like, and how does it work? Chris Smith spoke to University of Cambridge vaccinologist Gordon Dougan about the science behind the vaccine...

Gordon - When we, as children, we see lots of diseases, for example mumps and chickenpox. And we also know that those diseases usually only occur once; so we get protected, or immune, to those diseases. And what a vaccine does, it takes the germ or the bacteria or the virus that causes that disease, and we make an inactivated form of that germ which is safe, does not cause a disease, but mimics the disease. The body gets fooled into thinking that it's been infected; it sees the bacteria, the virus, the germ, and induces protection against the disease so we become immune.

Chris - How long does it normally take to make a vaccine then? Say I discover a disease, or we've got a disease in the population and we decide, "this is a big problem, we're going to fund a vaccine, we're going to make a vaccine." How long would that journey normally take then?

Gordon - Well the reality is it can take a long time. The average time from discovery to making a vaccine can be up to 10 years or even longer. And as you start to make the vaccine, it becomes more and more expensive as you try to develop the vaccine, and that puts a lot of people off trying to make vaccines. But, there are different stages to making the vaccine, so we could consider trying to shortcut the time that it takes. But the real important thing with a vaccine is it has to be safe.

Chris - And how do you prove that it is?

Gordon - You have to be very careful, in the sense that you have to use your own sense and scientific knowledge to create a vaccine which will not cause any side effects. You then take it through what we call the preclinical stage, which means we test in every different way we can possibly do to see whether it would a) induce protection, but b) also that it wouldn't cause side effects. And then we take it eventually into studies in humans: first of all in very small numbers of humans, but then gradually ramp up to try to see if we can vaccinate larger and larger numbers of people in a safe manner.

Chris - So what challenges are we facing trying to make a new vaccine against this new disease, this new coronavirus, that's the cause of COVID in some people?

Gordon - I think the main challenge is that we've never made a vaccine against a coronavirus before. We've tried to make vaccines against coronaviruses in animals but we haven't got any of them to work so far. But we do have a lot of knowledge about how to make vaccines against viruses, and lots of different tricks if you like to try to make them. And so what we are doing now is we'll be taking each of those approaches and trying them out systematically to see if we can get one vaccine that will induce protection.

Chris - And what's actually being pursued at the moment? Who's working on this and in what sorts of numbers?

Gordon - It's incredible really in that there's probably at least a hundred different groups of people around the world trying to make a vaccine. And they're taking a number of approaches, but there's about four different types of approaches. There's what we call a live attenuated vaccine. If you remember the polio vaccine you get as a child on a sugar lump, it's what we call the modified form of the disease-causing agent, the germ, which can be seen by the body as the causative disease agent; but it doesn't cause disease. The second way you can do it is you can actually inactivate that germ, that bacteria or virus, or take a small portion of that bacteria or virus; and that mimics the infection a different way. The last two approaches are slightly more complicated. One is what we call a vectored vaccine, and that's the approach being taken by the Oxford group which has gained so much publicity. And there you take the protective part of the virus, put it into another virus that might infect chimpanzees or other animals, but not humans; that delivers the vaccine into the human and induces protection. And the last form is a very novel form which is actually a genetic vaccine, the DNA- or RNA-based vaccine: in that you inject the DNA or RNA and you allow your own body to make parts of the virus that can protect you and induce immunity.

Chris - So when you say you inject bits of DNA or its chemical relative RNA, are you saying you take the genetic message for the, say, outer coat of the virus; and you put that genetic message into the body, and our own cells pick that up and decode it, and then show that to the immune system as though you'd injected the virus for real?

Gordon - That's exactly what you're doing. You try to package it in a little package that looks like a virus or a bacteria, you inject it, and the body is fooled. It basically starts making parts of the virus in the way would make normal proteins and other parts of the cells of your body during normal life. So you're really fooling your body with a genetic tool, if you like; a gene tool.


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