Inhaled vaccine prevents COVID in monkeys

Nick Petrić Howe

Hello and welcome to an extra edition of the Nature Podcast. Today some new research has been published about how vaccines that boost mucosal immunity could play a key role in fighting COVID in the future. Like many of you listening, I got COVID a couple of years ago. Now, I was lucky, I didn’t get severe symptoms. It wasn’t a great experience, but nothing that a week of feeling sorry for myself couldn’t fix. And that was likely because I was vaccinated.

Dan Barouch

The current COVID-19 vaccines provide substantial protection against severe disease, but they really don’t provide much protection against acquisition of infection or protection against mild symptomatic infection.

Nick Petrić Howe

This is Dan Barouch, a researcher of vaccine development at Harvard Medical School. Now, in an ideal world it would have been better to not get COVID in the first place, something which the current vaccines don’t really prevent from happening. But today in Nature, Dan is publishing a paper about how changing the way a vaccine is put into your body could stop you from getting COVID at all. He and his team were interested in whether boosting mucosal immunity — the response your immune system mounts in parts of the body with mucosal surfaces, like the mouth, nose and lungs, you know places where the virus first meets the human body — and how that could prevent infection altogether. Now there’s some evidence that this would be an effective strategy, but there’s a lot researchers don’t know about mucosal immunity. So, Dan and the team were interested to see if giving previously vaccinated rhesus macaques — a good model of human immunity — vaccine boosts into different parts of the body could help increase that immunity and prevent infection. For example, could administering a vaccine boost into the lungs — through inhalation — increase mucosal immunity better than via an intramuscular injection? And then could this prevent the macques getting COVID as a result? To find out, I called Dan up, and he explained to me what he and his team found.

Dan Barouch

What we showed was that when we gave the vaccine by the intramuscular route, we substantially increased both antibody and T cell responses in the peripheral blood, which is exactly what you would expect. However, intramuscular boosting only had a modest impact on antibody and T cell responses in the mucosa. Interestingly, intranasal boosting, didn't do much better. But where we saw a very major difference is when we administered the vaccine by the intratracheal route directly to the lung. And in animals that received the boost by the intratracheal route, we saw a vast improvement in mucosal antibody titers as well as mucosal T cell responses.

Nick Petrić Howe

Just so everyone is on the same page, like when you say you're giving it in this sort of intratracheal way, like, how would that work? I think people are familiar with vaccines maybe injected and that that sort of thing. But how would you administer one in this way?

Dan Barouch

In humans, the translational route would be inhalational. So, it could be delivered by something like a asthma inhaler. It's clinically translatable, because, for example, there is one vaccine made by the company CanSino in China that has been studied by the inhalational route. And they conducted a Phase 3 study that's now published, showing that inhalational delivery is safe and immunogenic and raises more potent mucosal immunity than intramuscular boosting and also is now approved for use in China. So, delivery of vaccines by an inhalational approach is definitely feasible.

Nick Petrić Howe

And in this case, you tested it on the macaques, and it was this intratracheal method that seemed to have the biggest benefit to them in terms of their sort of protection from SARS-CoV-2.

Dan Barouch

Yes, so, after we challenged the macaques, which was by intranasal and intratracheal routes — which is a standard way of challenging macaques with SARS-CoV-2 — in the group that received the boost by the intratracheal route, direct delivery of the vaccine to the lung, we saw near complete protection against infection.

Nick Petrić Howe

And just to be clear, as well, like when you say near complete protection, these macaques they just weren't getting COVID.

Dan Barouch

Well, a couple of the animals had a very low amount of virus for one day. And it's not clear whether that represents a very low level of virus replication, or whether we were just detecting the input challenge virus that we installed in that area a day prior. So, it's hard to really differentiate that completely, but substantially improved protection that was near complete or complete.

Nick Petrić Howe

And so how does this work? Is it just as you say, there's increased immune cell activity in these regions that you don't get when you inject it in the muscles? What's the sort of key difference do you think between this and any other route?

Dan Barouch

We did look at inflammatory patterns and cells in the lungs. And we were able to show that the intratracheal boosting resulted in a substantial and sustained activation of inflammatory responses NK cells, T and B cells in the lungs. And we believe that is likely the reason why we saw such a profound increase in antibody and T cell responses in the lung, as well as in nasal swabs.

Nick Petrić Howe

And so, you know, you did this work in macaques, but they are quite a good model for humans, right? So, what would be the next steps to get this into people who might need it?

Dan Barouch

Well, to some extent, it's already in people — not in the United States — so, this strategy is already being explored in humans. And I think that there is a lot of appetite now a lot of interest now to try to develop improved vaccines that can actually block infection, as opposed to vaccines that only prevent severe disease. And so this is one strategy that can and should be explored in humans.

Nick Petrić Howe

But in terms of like the next steps for the research, like what do you need to do next?

Dan Barouch

So, the next steps for the research are really to try to explore the mechanisms of how the mucosal immune system functions. There is very little known about that. And there's a lot less known about how immune responses are primed and boosted and maintained, have mucosal surfaces compared with in the periphery. So, one objective is to learn more about mucosal immunity from a basic research standpoint and develop clinical trials in a controlled way to really see if we see a similar phenomenon in humans.

Nick Petrić Howe

And so broadly, then, what do you think your results mean for our vaccination strategies going forward?

Dan Barouch

I think our results add to the growing body of data, suggesting that mucosal routes of vaccination really should be considered and perfected and utilised because only through mucosal routes of vaccination, are we seeing the high levels of mucosal antibodies and T cells that are needed to protect against infection with a virus as transmissible as SARS-CoV-2 Omicron.

Nick Petrić Howe

That was Dan Barouch, from Harvard Medical School, in the US. For more on that story, check out the show notes for some links. And that’s all for today, but we’ll be back at the usual time next week with our annual festive spectacular. See you then!