The mRNA Vaccine Revolution

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

Later in the hour, a conversation with author Loren Grush about women pioneers of the space program. But first, 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 spray?

Joining me to talk about what researchers are working on for both COVID and other diseases is Dr. Eric Topol. 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.

ERIC TOPOL: Thanks, Ira. Great to be with you again.

IRA FLATOW: 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.

ERIC TOPOL: 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 MMS– that is, a SARS-COV-2 nasal vaccine. And they did this with some ingenious work.

As you know, Ira, 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 prolines, they used six prolines. And they also, of course, went to the intranasal route, which we’ll talk about. And 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 variants.

IRA FLATOW: So is it just a cocktail of several different vaccines mixed together or is it one molecule that somehow works on all three?

ERIC TOPOL: Well, it’s basically adapted from the MMR vaccine– the mumps, measles, rubella. So it’s taking that trio, but switching out the rubella to COVID and then 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-proline substitution, but that I think is really what made this so stabilized.

IRA FLATOW: Can we get this vaccine yet?

ERIC TOPOL: I wish. No. It needs to go into clinical testing. And 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.

IRA FLATOW: Such as?

ERIC TOPOL: 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 III definitive trials that we’re waiting for a readout.

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 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.

IRA FLATOW: Yeah. Could you get one with chickenpox, flu, COVID in there, sort of a triple?

ERIC TOPOL: 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–

IRA FLATOW: Right.

ERIC TOPOL: –but there are going to be vaccines– there already are– RSV and flu, 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.

IRA FLATOW: 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 or the Pfizer boosters? Is that significant?

ERIC TOPOL: I think it is, Ira. It’s not entirely clear. But as you know, from all the prior work with mix-and-match vaccines, when you’d have a protein or an adenoviral vector vaccine mixed with an 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– most people, of course, have had mRNA vaccines– might give an extra kick, maybe a more durable– certainly 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 head-to-head trials like this. But if we just extrapolate from the prior work with these mixes, it looks like it has an edge. And that would be good.

IRA FLATOW: You write 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 mRNA vaccine, from cancers to chickenpox– everything there.

ERIC TOPOL: Right. Well, this is something that I think has been missed with this Nobel Prize to Karikó 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 their published work back in 2005– you know how we were talking about substituting the two prolines– well, what Karikó did was substitute a pseudouridine in the mRNA, 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 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.

IRA FLATOW: Yeah, I’m looking at your list– rabies, chikungunya, influenza, RSV, Zika, CMV.

ERIC TOPOL: They’re all in clinical trials. This has just opened up a whole new platform that wasn’t really conceivable until we learned through Karikó and 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.

IRA FLATOW: Let’s look into the future. I mean, look into your crystal ball and tell me what we might be seeing 5 or 10 years from now.

ERIC TOPOL: 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 cancer– we know cancer is so much a defect of 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. Let’s say they have tumor DNA in their plasma– the earliest possible way to diagnose they had cancer– or they have high risk because of their genome variants, you could give them a vaccine to prevent cancer from ever developing. Wouldn’t that be exciting?

IRA FLATOW: Or spreading if it’s already started to spread?

ERIC TOPOL: Exactly. That would be, with the tumor DNA, 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.

I’m really excited about these tolerogenic vaccines that– basically, the reverse vaccines– that prevent the autoimmune diseases from occurring or treat them far better than we can today.

IRA FLATOW: Like diabetes and other things like that?

ERIC TOPOL: Yeah. I mean, rheumatoid arthritis and lupus and multiple sclerosis, and the list goes on and on. This is a huge issue because right now we rely on immune suppression, and that is only partially effective. The disease progresses. But what if we could prevent that?

And these are some things that– if you go fast forward– 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 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.

IRA FLATOW: Well, we hope to have you back, Eric, to talk about all that.

ERIC TOPOL: It’s great to be with you again.

IRA FLATOW: 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.

When we come back, talking about the six pioneering women of the astronaut program. Stay with us. This is Science Friday, from WNYC Studios.

Copyright © 2023 Science Friday Initiative. All rights reserved. Science Friday transcripts are produced on a tight deadline by 3Play Media. Fidelity to the original aired/published audio or video file might vary, and text might be updated or amended in the future. For the authoritative record of Science Friday’s programming, please visit the original aired/published recording. For terms of use and more information, visit our policies pages at http://www.sciencefriday.com/about/policies/