Science Friday - The mRNA Vaccine Revolution

Episode Date: October 16, 2023

You’ve probably heard that there’s an updated COVID-19 vaccine on the market, and maybe you’ve already gotten your updated booster. But there are new kinds of vaccines in development that go beyond just tweaking protection to better cover circulating variants.In one promising development, researchers adapted the decades-old MMR (measles, mumps, and rubella) vaccine into one covering measles, mumps, and multiple variants of SARS-CoV-2—and, rather than a shot, they delivered that experimental vaccine via a nasal spray.Dr. Eric Topol, founder and director of the Scripps Research Translational Institute, joins Ira to talk about the approach, the advantages of nasal vaccines, and other vaccines on the horizon that make use of the mRNA technology that was the focus of this year’s Nobel Prize in Physiology or Medicine. Topol hopes that the mRNA approach will be widely applicable to a range of diseases and conditions—from conventional pathogens to cancers and autoimmune disorders. To stay updated on all-things-science, sign up for Science Friday's newsletters. Transcripts for each segment will be available the week after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

Could the MRNA technology that brought us rapid COVID vaccines open the door to vaccines against a host of other pathogens? There are many. We never had a vaccine. Not just that it took a long time. That's becoming more realistic than ever before. Today's Monday, October 16th, and today is Science Friday. I'm SciFRI producer Charles Burgquist. MRNA technology caught the attention of the Nobel Prize Committee this year,

but it's a lot more than just updated COVID boosters. A whole range of vaccines are under development from everything from Lyme disease to cancer, all based on those advances in MRNA. We'll talk about it. We'll also talk about an early trial of a triple vaccine against measles, mumps, and COVID that's delivered through the nose. Here's Irafledo. You've probably heard that there's an updated COVID vaccine on the market, right?

Maybe you have already gotten your booster, but there are new kinds of vaccines and new approaches to them under development. I mean, what if one dose could protect against several illnesses? And what if that dose didn't have to be a shot, but a nasal spread? Hmm. Joining me to talk about what researchers are working on for both COVID and others' diseases is Dr. Eric Topal. He's the founder and director of the Scripps Research Translational Institute. He's professor of molecular medicine and executive vice president of Scripps Research in La Jolla, California.

Welcome back, Eric, to Science Friday. Thanks, Sarah. Great to be with you again. Nice to have you. You recently wrote about a trivalent nasal vaccine that showed efficacy against COVID strains, measles, and mumps. Tell me about that. Sounds exciting. Yeah, it really is. I'm still blown away by this report from Ohio State. What they did is they took the MMR vaccine, which, as you know, has been out for 50 years, very safe. And they morphed it into an MMR vaccine. And they morphed it into an MMR vaccine. MS, that is SARS-CoV-2 nasal vaccine. And they did this with some ingenious work. As you know, in the vaccines that we use, they substituted two proline bases for the spike critical portion so that it will get into the cells better and be stabilized and elicit orders of magnitude more immune response. So what the Ohio State group did, they did not just two proline, They use six proletes. And they also, of course, went to the intranasal route, which we'll talk about it.

That's a much better way to go with what we need right now. And so they got superior antibody and T-cell response to all three pathogens across multiple experimental models, not just the mouse, but also the Syrian hamster. So they really had quite a demonstration of the potential for this triple-pathogen intranasal vaccine against all of the known major variant. So is it just a cocktail of several different vaccines mixed together, or is it one molecule that somehow works on all three? Well, it's basically adapted from the MMR vaccine, the mumps measles, Rubella. So it's taking the trio, but switching out the Rubella to COVID. And then we're going intranasal. And of course,

this critical thing, the 6P, which I think we had known that the 6P could be better than the 2-P substitution, but that I think is really what made this so stabilized. Can we get this vaccine yet? I wish. No, it needs to go into clinical testing. I wish it would go in quickly. There are so many great candidates like this one. This one's unique, Ira, because of the triple pathogen.

But there are many others just against COVID that look exceptionally. alluring. Such as? Well, if you go the nasal route, which is what I think is imperative, given that our biggest concern now is getting infections or reinfections. And we don't have a good way to do that because even the updated booster that you mentioned isn't so durable against infections. It's good against, of course, severe COVID, hospitalizations and deaths, but the effect against infections is temporally limited. And so, we need a nasal vaccine that basically blocks the virus from getting into our upper airway. And that's what nasal vaccines do. There are some that are already out there. And there are many candidates that

are in the process of phase three definitive trials that we're waiting for a redout. And they likely should be effective against all variants because they all work through the upper airway. And they rely on our mucosal immunity. That is a separate type of antibody pathway known as IGA. And the shots just don't get us there. They don't work locally. They work, you know, across the whole body through our bloodstream. So we really need nasal vaccines and hopefully sometime next year. We may not get this triple one that we discussed, but at least one against COVID would help. Yeah, could you get one with chicken pox, flu, COVID in there, sort of a triple? You're getting at another point, which is in the future.

You know how people are getting now both the flu and COVID shots together. Right. But they're going to be vaccines. There already are. RSV and flu and COVID that are in development, gone through clinical trials. So the likelihood of just getting one shot is going to change. Hopefully what we're going to see is much better, more durable. shots that are against not just COVID and all of its potential variants, but across the other

respiratory viruses that we are concerned about. While we're on the topic of vaccines and COVID vaccines in particular, the updated Novavax vaccine was recently approved. So people have a choice of that, right, as opposed to the Moderna with the Pfizer boosters. Is that significant? I think it is. It's not entirely clear. But as you know, from all the prime, work with mix and match vaccines when you'd have a protein or an antiviral vector vaccine mixed with a mRNA vaccine, almost invariably it led to a better immune response. That is, it amped it up because basically the body was seeing something different to rev up the immune response. So that's why I think the Novavax, for most people, of course, have had

MRNA vaccines might give an extra kick, maybe a more durable, certainly, you know, another incremental protection. So I think it's a good thing. Whether it is really that much different, we don't know, since there aren't any, you know, head-to-head trials like this, but it would just extrapolate from the prior work with these mixes. It looks like it has an edge, and that would be good. You're right in your substack commentary about the Nobel Prize in Physiology or Medicine,

and what it really was signaling, and I'm going to quote you, in many ways, the prize may someday be viewed as a promissory note for the unprecedented expansion of mRNA's utility to promote or preserve human health in the future. And you have a whole list in your commentary of all the different diseases that might be amenable to an MRI. vaccine from cancers to chickenpox, everything there. Right. Well, this is something I think has been missed with this Nobel Prize to Carricko and Weissman because the thought is, oh, well, that's just for their fundamental work that led to the COVID

vaccines with MRNA. But that's not really what it was about. The Nobel Committee spoke specifically about the MRNA platform because until they're published work back in 2005, when they, you know how we were talking about substituting the two proleins? Well, what Carrico did was substitute a pseudo-uridine in the MRI, which basically led to blocking the usual, very vicious inflammation immune response. So that has basically made MRNA the platform that it is today, not just for COVID, for vaccines against so many different pathogens.

But as you mentioned, now we're in trials, clinical trials, multiple RNA vaccines against cancer, some with already promising results of revving up the immune system better than we can with current drugs, but also blocking our immune system for autoimmune diseases, improving the delivery for genome editing. And the list just goes on and on. Yeah, I'm looking at your list.

rabies, chicken gunya, influenza, RSV, Zika, CMV. They're all in clinical trials. This is just opened up a whole new platform that wasn't really conceivable until we learned through Caracuan Weissman that you could just give MRNA as long as you made a substitution that was better than nature, which is what the theme here is, you could get away with it. And we talk about messenger RNA. You had a message that could do versatile things. Let's look into the future. I mean, look into your crystal ball and tell me what we might be seeing five or 10 years from now. Well, I think what we've learned, and of course, COVID helped push this over the goal line,

is that MRNA therapies are going to be part of our armamentarium. And basically, we will see a far better approach, for example, to Canada. We know cancer is so much a defect over our immune system to prevail over the cancerous cells. And so this is just one way, among many others, to get a far better immune response. And what we're really talking about is not just treating cancers, but the exciting potential in people at high risk of cancer. You know, let's say they have tumor DNA in their plasma, the earliest possible way to diagnose they had cancer, or they have, you know, high risk because of their genome of variants,

you could give them a vaccine to prevent cancer from ever developing. Wouldn't that be exciting? Or spreading if it's already started to spread? Exactly. That would be, you know, with the tumor DNA in the cell free in the plasma. But we're going to see things like that that we could hardly envision before cancer just being one example. You know, I'm really excited about these tolerogenic vaccines that basically are the reverse vaccines that prevent the autoimmune diseases from occurring or treat them far better than we can today. Like diabetes and other things like that. Yeah, I mean, you know, rheumatoid arthritis and lupus and multiple sclerosis.

And the list goes on and on. And this is a huge issue because right now we rely on immune suppression. And that, you know, is only partially effective. The disease progresses. But what if we could prevent that? And these are some things that are, if you go fast forward, you know, we've got some new opportunities we didn't have before. Plus, just going back to the pathogens, there are many.

We never had a vaccine, not just that it took a long time, but we've never been successful. And now that opens up, you know, almost all pathogens in the future, like a universal flu vaccine. Wouldn't that be great? And that's becoming more realistic than ever before. We have Project NextGen that the White House worked very hard, Ashish Jha and colleagues, to get $5 billion to support nasal vaccines and better, durable, less side effect, pan-variant COVID vaccines. So hopefully in the months ahead,

we're going to see an outgrowth of that investment. And I think we can look forward to, I hope, better vaccines, not just against COVID, but well beyond infectious diseases. And that's really enthralling. Well, we hope to have you back, Eric, to talk about all that. It's great to be with you again. Eric Topol, founder and director of the Scripps Research Translational Institute. He's also a professor of molecular medicine, executive vice president of Scripps

Research out there in La Jolla, California. And that's it for today. Lots of folks helped make the show this week, including Melissa Mayers, Daniel Johnson, Beth Ramning, Nehima Ahmed, and many more. Next time, a tricky question. Is meth real? Thanks for listening. We'll see you soon on Science Friday.