We begin in the Netherlands, where researchers are developing an antibody nasal spray to help combat influenza, and it’s shown great promise in human clinical trials. It’s hoped the spray – which targets parts of the virus common to all strains of the flu – could also help tackle future pandemics. Even more exciting is that the same technology could be turned on another seasonal lurgy: the common cold. A company called Leyden Labs is behind this exciting development, and their CEO, Koenraad Wiedhaup, has been telling Chris Smith all about it…
Koenraad – We’re developing nasal sprays that people can take during a flu season to be protected against these different viruses. These contain antibodies that can, you know, protect people against not just one type of flu, but actually the whole set of influenza viruses, and that’s what we’re developing.
Chris – That’s intriguing. So effectively, you have made in a lab the sort of immune response I would make if I caught flu for real, and I’m spraying something similar up my nose on a daily basis, and then if flu does try to invade, those antibodies are there and stop it.
Koenraad – Exactly. What’s also important by directly bringing these antibodies to the nose is also using unique antibodies that can protect against all these influenza types. So we all know that, you know, every year there’s, you know, we have to take another flu shot because every year there are different flu strains that are attacking us, but with this we can really use one, which is important for the seasonal flu, but also if we go back to our pandemic times that we can all remember, then we’re also ready for a potential pandemic flu virus as well, like avian flu.
Chris – These antibodies effectively hit bits of the virus that is invariable. So from one flu season to the next, this doesn’t change. So you’ve got an antibody against that, it will always work effectively.
Koenraad – Exactly. And that took decades of work to actually try to find these antibodies that are so broad that they can protect against all these influenza strains. But added to that, we bring that in the nose where these viruses attack us, so that we stop the infection there immediately, while vaccines mostly work when the virus is already in the body. So it’s, of course, easy to stop somebody just breaking into the house right at the door, then trying to get them, you know, when they’re already in the living room.
Chris – I like the analogy. The thing is, there are lots of routes into the body for flu. It can even infect the surface of the eyes and give you conjunctivitis. Yes, you can sniff it up. You can also just breathe it in through an open mouth. So, can you get enough protection from putting these antibodies just in the nose, that this makes a clinical difference?
Koenraad – Absolutely. And there maybe have become a bit more technical, but these viruses indeed come in, you know, through the nose, but also through the mouth and sometimes through the eyes. What we’re not trying to do is just stop them from coming in in the first place, like a face mask. What we’re actually doing is taking away the fertile ground that these viruses need to really replicate first when they come into the body. So they typically land in the back of our throats after they come in, even if they come in through the mouth. And that’s where they replicate fast, and only then can they also affect the further body and the lungs, for example. And what we’re doing with these nasal sprays is that we put these antibodies at that place. So we take away the fertile ground for them to replicate in the beginning.
Chris – How long do the antibodies sit there on the surface, giving that protection after you dose with them?
Koenraad – So what we’re working towards is that people can take a daily spray. Like, for example, you know, I have seasonal allergies, so pretty soon when spring arrives again, I take my, you know, daily spray to be protective against these allergies. So this would be the same, that people can take the daily spray and during that time they’re protected against these viruses. That’s what we’re working towards.
Chris – And what sort of data have you got that that’s achievable?
Koenraad – Yeah, so we very recently published data where we now see that this really can work in humans. So we have done clinical trials where we see that it’s well tolerated, so it has a good safety profile. But then also we see that we can achieve these high antibody concentrations in our nose, throat area, to actually have that protection, and that we can correlate with the work that we did before in the lab, but also with other studies that we did, where we see that that is enough to then also protect humans against these different viruses. So that’s a clear breakthrough that we just published.
Chris – Was this a challenge study, as in you protect some people and then you throw a certain amount of virus at them to see if it breaks through? Or was this a natural experiment where you take a group of people, ask them to use the agent, and you know how many people you’d expect to catch the flu, and you compare that to how many actually do, and you can work out what the efficacy is? How did you actually generate that data?
Koenraad – We actually are measuring the antibody concentrations in the noses. And then we take out samples of these noses, and we see that those samples are still neutralising these different viruses. And that we could correlate with the work that we have done before, where we know how much antibody is basically needed to protect against these different viruses.
Chris – But that’s still not a replacement for a person walking around in the real world, encountering flu for real, and being protected. That’s got to be the next step.
Koenraad – That is absolutely the next step. So we’re working through to start those kinds of studies as well. And that’s the next step to further develop this.
Chris – Given you’ve managed to do this for flu, you think, and obviously, we’re waiting on the subsequent trials to prove that it does work in the real world. Can we then extend this into the realms of other nasties? Could you make a suite of antibodies against the commonest causes of the common cold, and people could protect themselves against that, too?
Koenraad – Yes, absolutely. We are working on an approach that would be able to protect against basically all airborne viruses. We’re working on a product that can protect against coronaviruses, not just SARS-CoV-2, but also other coronaviruses. And about 20 to 30% of our common colds are actually caused by coronaviruses. But then, also looking at other viral families. Of course, the future that we want to work towards is having one spray that can protect against all these viruses. But we take it, of course, step by step.