Future-proof vaccine for COVID variants down the line

As coronavirus infection rates climb again, a future-proof coronavirus vaccine that can protect against variants of the virus that don't even exist yet - is welcome news. Jonathan Heeney and Sneha Vishwanath have used the genetic sequences collected from the viruses that circulated during the pandemic to spot parts of the virus structure that have never changed: they’re said to be "conserved". The virus is obliged to keep these components the same because they carry out critical functions. Altering them would disable the virus, so in this respect, they're an Achilles Heel, that will be present in all variants of the virus, including those that crop up in future. But the virus normally keeps these structures hidden from our immune systems, for obvious reasons, so most people don't produce an immune response against them following a natural infection. But what the Cambridge duo have done is to glue a slew of these structures together into a cocktail that the immune system can see, producing a powerful response that, in their test animals, remains effective for at least two years and works against the multiple variants of the virus they've tested. It's now in early clinical trials…

Jonathan - The problem is that viruses change faster than we can manufacture vaccines and the vaccine is way behind the virus. And now we've seen that throughout the COVID pandemic with all the waves of variants. So we needed a solution to get ahead of the virus.

Sneha - We sort of assembled all the information that is out there for viruses which behave or look like the current coronaviruses and then look into what is common between all these viruses and what are the regions which would induce a good protection or an immune response against these sets of viruses.

Chris - So these are bits of the virus that are always there. It doesn't change them. So if you hit them with some kind of immune response, you should hopefully work against what's circulating now, but what hasn't even evolved yet.

Jonathan - Exactly. We're trying to target the Achilles heel, that part of the virus that is essential for binding to its receptor, or replicating, or exiting the cell. Those are key structures like the door handle that cannot be changed for this particular virus.

Chris - You are going then for bits of the virus that don't change as it evolves. If I catch it once, why do I not make a response against those things and then get protection for life?

Jonathan - Some lucky people do make those responses. That would explain why not everybody in the household would get ill at the same time despite their common exposure.

Chris - I'm with you. So some people do make responses against these bits of virus, but the majority don't. And you are coming up with ways to make the majority make responses against the bits that most people wouldn't but which are always going to be there.

Sneha - Exactly, what we are trying to do is making sure that each and every individual sees that conserved part first so that it generates a better immune response against that.

Chris - How do you know what those bits are?

Jonathan - We are fortunate to have a huge amount of sequence data. As you know, this country and many other countries, we're following these viruses by sequencing them and we get this data and we line it up and compare where those changes are happening and we identify those regions which aren't being changed and those are the regions that we target.

Chris - And how do you turn the identification of this region and this region and this region, which are those Achilles heels, into a potential vaccine?

Sneha - So once we identify these regions, these genes specifically that act like a recipe for the vaccines when it gets expressed it can form that protein and it can induce that immune response.

Chris - Do you put the gene into sort of cells in culture then to make the protein the bit of the viral coat or the innards of the virus that you want to turn into a vaccine?

Jonathan - That's one of the first steps in the process, correct. So we take the code and then we test those in cells to see if we've got the right structures.

Chris - And then how do you know if it's going to work as a vaccine?

Sneha - So once we check it's getting expressed in cells, we basically immunise different animals with these particular vaccines which express our genes and then we make sure we check whether they are generating appropriate immune responses or not.

Chris - These animals, do you then try and infect them with coronavirus infection or do you collect the antibodies that they make and see how they work?

Jonathan - We first collect the antibodies that they make and check to make sure that those antibodies will block variant A, B, C right down to Omega. And we've shown that we can protect animals with these vaccines.

Chris - How good are they?

Sneha - They're quite good. <laugh>

Chris - Only quite <laugh>. Jonathan's rolling his eyes going, 'no, they're much better than that.' <laugh>

Sneha - Yeah, they're much better than what we have right now currently in the market because it targets just not one virus. It also targets multiple viruses. So giving us better protection than what's out there in nature right now.

Jonathan - Everybody's heard of antimicrobial resistance and you know that if you use penicillin for instance, there's a good chance that a bacteria may get around that penicillin. And to treat people with multiple complex infections, we'll use combinations of drugs. Well we use that similar strategy with our vaccines. So we'll add in Achilles heel A, Achilles heel B and Achilles heel C, all into our vaccine so that we've locked as many doors as possible.

Chris - That's neat. So rather than just target one thing because you've got a whole bunch of vulnerabilities and you hit them all at once in the same cocktail, the chances of it being able to change all of them all at once, even if it could, is so remote that it's not going to.

Jonathan - Exactly. And that's our strategy now. So we are going to take these structures and our new generation of vaccines has got those cocktails in them.

Chris - One of the problems has been the longevity of the response. We've seen people get vaccinated and then within months they appear to be infectable again. How long lasting is the response that you get to these vaccines when you put these into your test animals?

Sneha - In test animals, it does show a good response up to like 24 months in mice. But I think that needs to be tested in humans.

Chris - Do you think this is scalable? Practical? Is this going to become the next thing on the market? This sounds promising.

Jonathan - We're hoping in order to get it to the market, we need a commitment, a long-term commitment because it's expensive. And to do that you need investment from pharmaceutical companies. So we'll be looking to partner with big pharma to help us get those studies done.

Chris - What's the timeline now? Now you've got this initial proof of concept. How long before we're able to realistically deploy this?

Sneha - We have started the phase one study, so once we get the results from that, I think maybe another two to three years. If everything goes in favour.