Could this nasal spray replace all your vaccines one day?

There’s the flu vaccine. The covid shot. The RSV shot… What if all of these—and more—could be combined into one universal vaccine? That’s what immunologist Bali Pulendran https://med.stanford.edu/pulendranlab.html is working on in his lab. For this episode in our Tech Camp series, Regina G. Barber https://www.npr.org/people/1082526815/regina-g-barber talks to him about how far he’s gotten, how far he has to go and why our ancient immune system is the key to it all. Plus they discuss how the vaccine may not be a shot at all—but a needle-free nasal spray. Sources: Mucosal vaccination in mice provides protection from diverse respiratory threats https://www.science.org/doi/10.1126/science.aea1260 Non-specific effects of BCG vaccine on viral infections https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(19)30197-1/fulltext Interested in more science of the future? Email us your question at [email protected] mailto:[email protected]. Support public media with NPR+ and enjoy perks for over 25 podcasts like this one. It includes perks like bonus episodes, early access, archive access, curated playlists and sponsor-free listening. Learn more at plus.npr.org http://plus.npr.org. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:17Speaker 01

  You're listening to Short Wave from NPR. Hey, Short Wavers, Regina Barber here.

• 0:24Speaker 02

  And Emily Kwong.

• 0:25Speaker 01

  And we're back with another episode of Tech Camp, our summer series scouting the technological frontier, tracking down the breakthroughs, experiments, and innovations that could change everything. And this episode, Em, we're talking to a scientist who's developing a universal vaccine, one vaccine to rule them all.

• 0:45Speaker 02

  That would be incredible because what we have now, of course, is a lot of different vaccines to protect against specific pathogens.

• 0:51Speaker 01

  Yes, that's right.

• 0:52Speaker 02

  So in this future, there would be no annual flu and COVID and RSV shots? There would just be one shot for everything? How is that even possible?

• 0:59Speaker 01

  Yeah, so Bali Pulendran, an immunologist at Stanford University, started seriously thinking about this in the late 2010s when he read a paper about tuberculosis.

• 1:08Speaker 02

  OK.

• 1:09Speaker 01

  So the paper found that people vaccinated against tuberculosis were actually protected from other infections like HPV.

• 1:15Speaker 02

  Whoa.

• 1:16Speaker 01

  And the TB shot could boost how effective vaccines were against diseases like the flu and yellow fever, too. And he wondered.

• 1:23Speaker 03

  Why is a vaccine that's being developed to protect against TB inducing such broad immunity that is able to fight other kinds of infections? I felt that there has to be some underlying mechanism that would explain this.

• 1:42Speaker 02

  That sounds like a scientist on the hunt.

• 1:44Speaker 01

  Yeah. And that led him to an ancient part of our immune system, one that treats all pathogens more or less the same. And using this knowledge, he and his team started making a universal vaccine, which they now have shown can work in mice.

• 1:58Speaker 03

  So this new universal vaccine that we've developed really is a radical departure from pathogen-specific vaccines.

• 2:07Speaker 01

  So today on the show, the future of vaccines. Gina talks to Bali about why the key may be in our ancient immunity and why a simple nasal spray may be the answer. And along the way, I get a little help from characters like Cinderella and the Cookie Monster to explain the immune system. You're listening to Short Wave, the science podcast from NPR.

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• 3:56Speaker 01

  OK, Bali, we're talking today about your ongoing research into whether scientists can develop a universal vaccine that protects against many infections. And the key here is activating a different part of the immune system from what, you know, a COVID or a flu vaccine would. What is that part of the immune system?

• 4:15Speaker 03

  That part of the immune system is called the innate immune system. Think of it as the Cinderella of the immune system. The innate immune system is a neglected part of the immune system. It hasn't received much attention for years. Why? Because really, not many labs were studying the innate immune system. But you know, it's the oldest immune system we have in our bodies. It's ancient. It's billions of years old, whereas the younger antibody-based or the T-cell-based immune system is only a few hundred million years old. That's still pretty old, but not nearly as old as the innate immune system. Now, the antibodies and T-cells are incredibly specific.

• 4:59Speaker 03

  Each antibody can only neutralize or bind one virus or one microbe. Same thing with T-cell. The innate immune system cells, such as macrophages or denrytic cells, can chew up pretty much anything and everything. They gobble things up.

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  Like Cookie Monsters.

• 5:19Speaker 03

  They gobble things like Cookie Monsters. They are like Cookie Monsters. And, you know, they are not very discriminatory in their taste. They don't go for the fine gourmet style of bacteria or virus. They pretty much eat up everything in the refrigerator, any kind of virus, any kind of bacteria, any kind of fungi.

• 5:40Speaker 01

  That's awesome. OK, so your team published a paper showing you could do this in mice with a nasal spray. Like, what's in this nasal spray?

• 5:49Speaker 03

  There are two components in this nasal spray. One, synthetic molecules that can activate cells of the innate immune system in the nose and in the lung. The other is an antigen. An antigen is a protein.

• 6:06Speaker 01

  OK.

• 6:07Speaker 03

  And these two components were able to activate the innate immune system. And that provided not only very broad protection against many different viruses, bacteria, and even allergens, but could sustain this protection for three months. And it goes back to this innate immune system, these macrophages in the lung that were supercharged so that they were able to gobble up any kind of virus or bacteria that came in through the nose into the lungs and chew them up very, very quickly and get rid of them.

• 6:45Speaker 01

  So these mice, like, were protected for three months against what? What kind of things were they exposed to?

• 6:52Speaker 03

  Influenza, SARS-CoV-2,

• 6:57Speaker 03

  other kinds of coronaviruses, bacteria such as Staph aureus, and some other kinds of respiratory bacteria, and even allergens.

• 7:08Speaker 01

  I'm just wondering about, like, future vaccines. If we had a universal vaccine, would this be an annual thing like the flu? Or like, could it be longer?

• 7:18Speaker 03

  I could see two broadly different types of application for this universal vaccine. So imagine a scenario where one could give this nasal spray during the winter months, and this would provide protection for about three months, maybe a bit longer, maybe up to six months, against flu, respiratory syncytial virus, COVID, the common cold. So very broad protection. So that's one scenario.

• 7:49Speaker 01

  What's the other scenario?

• 7:51Speaker 03

  The other scenario is during pandemic times.

• 7:54Speaker 01

  Got it.

• 7:55Speaker 03

  Let's say it's the year 2030. And let's say we have a new virus that is spreading as quickly as COVID did back in 2020, but causing much more severe disease. We wouldn't have nine months to try and make a vaccine that was highly specific to that virus. And so we'd have to come up with something else. And here's where I think this universal nasal spray, if it's administered broadly across the populations at the very earliest signals of a pandemic, could have a profound impact on curbing the disease as a stopgap measure until such time as the conventional vaccines are developed,

• 8:40Speaker 03

  which could take months, probably longer.

• 8:43Speaker 01

  And you said this work has been done in mice. And the first step is to show that it could possibly work in humans. But how long are we from that? Like, how long do we have to go to get this to start working in humans?

• 8:55Speaker 03

  So we are now in the process of fundraising to do a human study to show proof of concept in humans that this vaccine could elicit broad protection. And I'm optimistic, I'm hopeful, that we can raise the funds. And what we would need to do is toxicology, meaning you do in rabbits, you do these experiments and have a toxicity profile, and then do a dose escalation study in humans. And then ultimately, we immunize humans intranasally with this vaccine and deliberately infect them with influenza under a clinical setting

• 9:40Speaker 03

  in what's called a control. Yeah. And then see if it works or not. And we're about, I'd say, about three to four years away from that.

• 9:47Speaker 01

  Do you think, just from those tests, but do you see a world where you have a universal vaccine that people are getting, like you said, in the winter months, within the next 10 years? Is that a hope? Is that a goal?

• 10:00Speaker 03

  It's certainly an aspirational dream, as in all cases. As in all cases, you know, it's a long and tortuous road to that. I mean, the safety issue is a major concern. We have to do many, many clinical trials, phase one, phase two, phase three, to assess whether these are safe, what are the adverse reactions. But I think what our current study has is a roadmap, an immunology roadmap and proof of concept in mice, that this is possible. It's not just theoretical. It's possible. The question is, how do you translate this safely into humans?

• 10:36Speaker 01

  So when you imagine a world where there is this universal vaccine, it's become a reality, how do you envision the impact?

• 10:44Speaker 03

  It's hard to overstate this. And, you know, I'm very close to it, so I'm not a person who's best qualified. But my hope is that it would have a transformative impact because it would be a radical departure from how vaccines have been developed over the last 230 years since Edward Jenner. And it's a whole new way of thinking about vaccines. So there's much to go before we come to that stage. As I said, safety is of paramount concern. We have to demonstrate safety rigorously in many human studies.

• 11:17Speaker 01

  Bali, thank you so much for talking to me about the potential of a universal vaccine.

• 11:22Speaker 03

  Thank you so much. That was wonderful to talk with you.

• 11:28Speaker 01

  Short Wavers, if you liked this episode, follow us on the NPR app or wherever you're listening from. This way, you'll never miss a new episode. We promise we'll always deliver you an interesting fact. This episode was produced by Burleigh McCoy and edited by our showrunner, Rebecca Ramirez. It was fact-checked by Tyler Jones, and Jimmy Healy was the audio engineer. I'm Regina Barber. Thank you for listening to Tech Camp from Short Wave, the science podcast from NPR. See you tomorrow.

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