The New Vision For Vaccines

IRA FLATOW: This is Science Friday. I’m Ira Flatow. In case you just joined us, we’re talking this hour about vaccines, and for the rest of the hour, the future of vaccination. Can what we have learned in developing COVID-19 vaccines change how vaccines are made going forward?

Joining me now are my two guests, Dr. Paul Duprex– he’s the Director of the Center for Vaccine Research, professor of microbiology, molecular genetics, University of Pittsburgh School of Medicine, of course in Pittsburgh, and Ryan Cross, Biotech Reporter for Chemical and Engineering News based in Washington. Welcome both to Science Friday.

RYAN CROSS: Thanks for having us.

PAUL DUPREX: Nice to be here.

IRA FLATOW: Nice to have you. Dr. Duprex, there’s a lot of focus right now on the mRNA vaccines. How do they fit into the overall vaccine toolkit? How did we get here from the days of the Salk polio vaccine?

PAUL DUPREX: Whenever you think to the past of Salk and Sabin, they had limited numbers of ways in which they could weaken viruses. And the technical term we use for that is attenuated viruses and make vaccines.

So for example, we’ve taught from Pittsburgh, as you’ve said. Salk worked here. He determined how to chemically inactivate the polio virus that he had grown. And that was the vaccine that was the first one to be generated for polio viruses and really has been instrumental in leading to the near eradication.

But, of course, first is not often best. And we need to have a number of different ways to make vaccines. So the Sabin vaccine was also used in the eradication program. And it, rather than being chemically inactivated, was biologically changed. What Sabin did was he weakened it by passing it in cells. And the virus changed.

And eventually, the virus, instead of causing the disease polio virus, it formed the ability to generate antibodies in the individuals. And again, when we’re talking about coronaviruses, antibodies are super important. So we had polio virus antibodies generated, but we didn’t get the disease. And that’s the real basis of a vaccination.

That’s where a lot of it started. These were empirical people who knew what they were doing. They were very systematic in their studies. But one of the things which is super-interesting about vaccines is we still don’t know how many of the great vaccines that we have work.

So for example, I work on measles. Worked in measles all my professional life. We still don’t know the molecular basis for why the measles vaccine is such a phenomenally good vaccine. So that’s the past. Fast forward to 2020-2021, the toolkit that’s available today is something that Salk and Sabin could only have dreamed about.

We can use the modern approaches of molecular biology. We understand how RNA goes to proteins. We understand how DNA goes to RNA, goes to proteins. And remember, the proteins are the things that the immune system recognizes. And that’s why we end up with super-cool and very different ways to make vaccines.

Now, I can answer the question about mRNA vaccines. Why they’re really interesting is because we have never, until like 2020, licensed an mRNA vaccine. Completely new modality, completely different way. What you’re doing is you’re not showing the person the shape of the virus by showing the inactivated virus or even the proteins from the virus.

What you’re doing is you’re using the person to be the factory to make the proteins, so that the immune system recognizes that spike protein we’re all too familiar with. And the immune system begins to make those antibodies against the spike protein, which, of course, decorates the outside of SARS-Coronavirus-2.

IRA FLATOW: Ryan, you follow the biotech industry. Is mRNA the big, hot new thing that Dr. Duprex is talking about?

RYAN CROSS: It is, and it has been for a few years now. I think people have been working on this idea of an mRNA vaccine or even an mRNA therapy for really decades. It really goes back almost to the time of DNA vaccines. But over the past 10 years, it started to pick up interest from biotech investors. And really, just a handful of companies– Moderna and BioNTech to name the two that we have approved here in the US now– have really invested billions of dollars in trying to make this experimental technology actually work.

And I think this is something that maybe gets lost in the shuffle of news, is that even though these are the first mRNA vaccines that have ever been authorized here in the US, they’re really built on the backbone of more than 10 years of work and a huge amount of investment in the technology.

IRA FLATOW: Would you have predicted, Dr. Duprex, at the beginning of all of this the success of the mRNA approach?

PAUL DUPREX: Of course, hindsight is a wonderful thing. But I honestly do believe if you had asked biologists to give you a number before the studies were presented and looked at by the FDA, I’m not sure that too many vaccinologists, virologists, epidemiologists, immunologists would have really picked the number 94%.

And I just love that hard work. And as Ryan has just said, this doesn’t come out of nowhere. It comes out of hard work, perseverance. It comes out of really good formulation, important delivery, all those bits to give us a completely new way to make a vaccine.

So I’m not sure that I would have said that it would have been as high, but I love the fact that it is as efficacious as it is. And I really hope that we continue to learn. Because what do we know? First generation becomes second generation. Second generation becomes third generation. We just get better at delivery. We get better at understanding.

So hopefully, this is just the beginning of a new way to deal with not just infectious diseases, but other sorts of diseases as well.

IRA FLATOW: Ryan, is anyone thinking of replacing existing vaccines that are not mRNA ones with mRNA ones?

RYAN CROSS: What I’m hearing is that a lot of our existing vaccines, our childhood vaccines, a lot of them are pretty good. And some of them have even almost eradicated the diseases they’re designed to prevent. And there’s probably not going to be a lot of motivation to replace those.

Some other vaccines, such as the flu vaccine, there’s a lot of room for improvement with that. It’s really hard to make flu vaccines because that virus is so much more variable and changes so much more quickly than even something like the new coronavirus. And it’s been really hard for vaccine makers to make a vaccine that matches the current genetic makeup of that flu virus.

Since mRNA vaccines can be made, designed, and manufactured so much more quickly, there’s a potential that they could be really revolutionary for flu vaccines. The companies are working on that right now. It remains to be seen whether they’re going to live up to that potential.

IRA FLATOW: Why would a big pharmaceutical company like Johnson & Johnson, who is working there on the third phase of a vaccine, a coronavirus vaccine, but it’s not an mRNA vaccine. It’s an adenoviruses vaccine. Why would they go in that direction, Paul?

PAUL DUPREX: The old phrase, “Don’t keep all of your eggs in one basket” is very important. I think Ryan’s point is well made. Just because we got 94%, 95% with the SARS coronavirus in an mRNA vaccine does not mean that that will be the same for influenza, for example.

So I think it’s really important to be creative, be developmental. Because I just don’t believe there’s ever going to be a one-size fits all approach to vaccination. We need to just think about it as adding to the tool kit, having abilities, different modalities that can be tuned for specific viruses.

Because remember, what we do know is viruses emerge. We’ve talked about flu. Why do we need to make flu vaccines again, and again, and again? Because viruses emerge from animals. And they also change within people whenever the people are infected.

So we need to be ready to be as adaptable as the viruses and the pathogens that we’re trying to fight. And you don’t have only one weapon in your armory whenever we are beginning to learn how evolutionarily clever these viruses are, SARS-2 is, how it makes deletions, how it makes changes, how it’s evolving already under this selective pressure. That’s why you don’t just have one vaccine approach.

RYAN CROSS: If you don’t mind me adding to that. These different pharmaceutical companies have all invested in different technologies. I think we’re really fortunate that before the pandemic, Pfizer had actually started working with BioNTech on mRNA vaccines for the flu. And those are still in a much earlier experimental stage. But because of that partnership that Pfizer had, they were able to pivot and start working on mRNA vaccine for COVID quickly.

Johnson & Johnson took a different approach, as you said, these adenoviral vector vaccines, which is not mRNA, but it’s sort of its own kind of genetic vaccine since it involves really taking a gene for that coronavirus spike protein and putting that in this shell of a common cold virus.

And you have this genetically engineered virus that you can also make pretty quickly, which moving a little more slowly than the mRNA vaccines. But still, compared to normal, quite fast. And we could really expect to find out whether that vaccine is effective or not next month.

IRA FLATOW: So aren’t the days of a dead or attenuated virus vaccine done with? It doesn’t sound like that, Paul.

PAUL DUPREX: I think they are not over. But we have to use the right vaccine, against the right disease, in the right way, at the right time. Remember as well, one aspect of the conversation which we should discuss is price. Not all of these vaccines are the same price. And we have touched a little bit on the fact that some of them have to be stored at very, very cold temperatures.

I think it’s really important whenever we’re having this conversation to remember that it’s just not about us. Whenever I say us I mean us in the United States. Virus somewhere the world is pretty much a virus anywhere in the world. And I think we don’t need to be told that based on this current pandemic. It’s not to blame where it came from in the world. That’s naive.

But what we have to realize is these are global problems. So therefore, we need to ensure– and again, during the development process, we need to ensure that we are developing vaccines not just for our part of the world, but for all of the world.

So when we make products which have to be stored at such a cold temperature or cost a lot of money, we are not looking after people who are equally valuable, have equal meaning, have equal worth in all of the world. And therefore, we’re not looking after this part of the world as well.

So we want to make sure that we don’t develop products that are too expensive. We want to make sure that vaccines are equitably distributed and that they can be equitably distributed. So again, that’s why you need to think about other modalities– adenoviruses, UV inactivated vaccines, inactivated vaccines, whatever way you make those vaccines. So that we have products for everyone, not just the privileged few.

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

Let me have you dream a little bit, Paul, about– let’s even go as high as a science fiction mode. What is the science fiction now, the really out there dream idea that people are having or you’re having?

PAUL DUPREX: One of the biggest challenges is viruses know through evolution how to be ultra sneaky. They are able to evolve pretty quickly. So we’ve talked about influenza. Wouldn’t it be wonderful if we could get to the point where we could get these cocktails that we’re ready to anticipate the viruses that may come as opposed to the viruses that are here.

The term that we use for that in the influenza world is universal influenza vaccines. Or the other word we can use as pan vaccines. Wouldn’t it be great if we had developed, because we knew it existed, a SARS-1 vaccine? But not just a SARS-1 vaccine, a pan coronavirus vaccine, so that we were ready for the next coronavirus?

And there was MERS, which is the next coronavirus. And then there was SARS-2, which was the next coronavirus. And there will be more. Wouldn’t it be wonderful if we eradicated measles, that we were ready with something just in case a new virus like measles virus, or polio virus, emerged from an animal reservoir.

Because that’s what happens. And making vaccines for the present is far from trivial. Dreaming about vaccines which have pan universal activities is certainly challenging. And that’s for the future. And I look forward to the day when such vaccines are made before the virus is not even known.

IRA FLATOW: And we’re looking at other companies. There was research being published this week talking about possibly using mRNA to treat other diseases, for example, cancer or other tumors. It seems to have crossed over now, Ryan, into these other areas.

RYAN CROSS: Yeah, a lot of these companies, like Moderna and BioNTech, have actually spent a lot of money and time working on things that are not infectious diseases over the past 10 years. They really have a lot of investment in cancer, in autoimmune diseases, even rare genetic diseases.

They think that they can use mRNA vaccines to basically give your immune system a mug shot of what your tumor looks like. Or they can also use mRNA to basically encode a drug or a protein that could treat a disease, not a vaccine, but a treatment.

I guess, maybe just to follow up on the sci-fi question from a minute ago, I was thinking about my answer for that as well. And it’s becoming harder and harder to envision these science fiction scenarios. Because the things that people are doing right now almost sound like science fiction.

People are working on universal coronavirus vaccines. People are working ahead to try to predict what kinds of viruses might emerge. And can we make prototype vaccines for those viruses right now, so that we can be ready to go, and maybe move even faster in the next pandemic? And it’s incredible and hard to believe, but also really inspiring to see that happen.

IRA FLATOW: Thank you both, gentlemen. This has been very, very informative. I’d like to thank Dr. Paul Duprex, Director of the Center for Vaccine Research, professor of microbiology and molecular genetics, University of Pittsburgh School of Medicine in Pittsburgh. Ryan Cross, a Biotech Reporter for Chemical and Engineering News based in Washington, DC. And they have a big issue looking back on a year of COVID science coming out later this month. You’ll want to look for that.

Thank you both for taking time to be with us today.

RYAN CROSS: Thank you so much.

PAUL DUPREX: Thank you very much, indeed.

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