Vaccines for viruses that haven't even evolved yet

Researchers at the University of Cambridge have developed a new vaccine technology which they believe could provide protection against a range of new coronaviruses, including even those that may not even exist yet. It’s hoped that the discovery could help curb future pandemics. It works by glueing key pieces of the virus outer coat that are shared by many different viruses onto injected nanoparticles; these train the immune system to recognise them. Here’s Rory Hills from the University of Cambridge’s department of pharmacology…

Rory - There are a variety of other coronaviruses in the same family that are lurking in bats and pangolins and other mammals that have the chance to cross over to humans. Our vision is to have a vaccine that can protect against those before they've actually crossed over to humans.

Chris - One scientist scarily told me during Covid that there are probably as many as 5,000 members of the coronavirus family, quite a high fraction of which might jump the species barrier. You're pushing on an open door, I'd say. How do you do it?

Rory - We use a protein nanoparticle as the basis of our vaccine and then we attach parts of different viruses to that same nanoparticle. The trick is we create a mosaic of all these different viruses and when you immunise with that, you train the immune system to go after the parts of those viruses that are shared. If we can train the immune system to go after those shared parts, we can protect against all of those viruses we have on the vaccine, but also against ones that aren't present and are just related.

Chris - Because those things, even though you've not seen them, have still got that same core part that those other things you did train the immune system on had and so you make a response that indirectly protects you against those?

Rory - Exactly right.

Chris - Didn't some people argue that during Covid that was naturally happening in the sense that there were some people who didn't get the virus or didn't get it badly and they made the case that those individuals had perhaps had one of the other common coronavirus infections and made a response to it that happened to protect them because they'd made a response to some of the bits that those other common coronaviruses share with the SARS-CoV-2 virus that causes Covid?

Rory - That's my understanding. Of the seven coronaviruses that infect humans, four of them cause the common cold. There are regions of those spike proteins on those common cold coronaviruses that can provide protection against SARS-CoV-2.

Chris - When you're trying to make your vaccines, how do you spot the bit that you're going to put onto your nanoparticle? How do you say, well, I'm going to have that bit and that's going to be a really good bit to go for.

Rory - We have been very conventional in that approach. We've just used the receptor binding domain of the spike protein, the RBD, and that's the tip of the spear...

Chris - This is on SARS-CoV-2?

Rory - SARS-CoV-2. Yes. We've taken that same protein on all of the other coronaviruses, and then the trick is we haven't necessarily gone through and tried to pick out the parts that we're trying to target. Just by the nature of having these eight different proteins on the nanoparticle, we train the immune system to go after the parts that are shared. So we don't have to know going in what those parts are.

Chris - Does it work?

Rory - It works remarkably well. It works better than we were initially anticipating. When we immunise animals with our vaccine, we end up getting responses that are neutralising against the viruses included and then also viruses not included. In fact, I've created a version of our vaccine that doesn't have Covid, doesn't have any closely related viruses to Covid, and we're still able to get a very strong response against Covid with that vaccine.

Chris - You mentioned you vaccinated animals. You put this in and they presumably make antibodies. How do you then make sure they're protected against this range of viruses?

Rory - There are three main outputs. The first one is the easiest one: that's just making sure that the antibodies that they make bind to the proteins that the virus produces. We use something called ELISA for that. The second one is called a 'pseudo virus neutralisation assay.' So we have essentially a modified version of the virus that's not dangerous, it just carries the single protein from a coronavirus, and we look at that ability to infect human cells in a dish when we add serum from mice that we've immunised with our vaccine.

Chris - That's got the antibodies in it that serum. You're then able to say, well, if that blocks that then, were that in the animal for real, they would be protected.

Rory - Exactly. And the third way is that we take the actual COVID-19 virus and look at its ability to infect human cells in a dish. We look at the protection that is conferred by the antibodies that we've raised in mice.

Chris - And that works?

Rory - It works brilliantly. I think if we think much more long term, the vision is that you could have a library of preexisting vaccines that protect against a group of viruses, have them validated for safety and efficacy and on the shelf ready to go in case of future pandemic.

Chris - People have been trying to do this for flu for decades. When I was a medical student, people were trying to do this and make the 'uni flu vaccine.' Can you now turn this on to challenges like flu?

Rory - That's certainly something that we're really interested in and I think it's something that we definitely want to strive for. A universal flu vaccine is a very substantial challenge. Flu has been with us for a very long time, it's diversified incredibly, and it's not just a matter of getting antibodies that bind, we also want to have them actually able to neutralise the virus.

Chris - You're saying flu is a harder nut to crack?

Rory - I think so.