S1E25 / A COVID Vaccine / Seth Berkeley & Peter Hotez

I'm Dr. Celine Gounder.

And I'm Ron Klain.

And this is Epidemic. Today is Wednesday, June 3rd.

It's called Operation Warp Speed. That means big and it means fast. A massive scientific, industrial and logistical endeavor unlike anything our country has seen since the Manhattan Project. Its objective is to finish developing and then to manufacture and distribute a proven coronavirus vaccine.

That's President Donald Trump on May 15th, making a huge promise.

We'd love to see if we could do it prior to the end of the year. We think we're going to have some very good results coming out very quickly.

In this huge promise, there's a huge problem. Scientists aren't magicians.

The challenge on this is obviously we're dealing with a new agent that we've only known about for now a little bit more than 4 months. So we're lucky we have over 100 vaccine approaches that are being worked on and already a handful of them in clinical trials.

This is Dr. Seth Berkley, CEO of the Gavi Vaccine Alliance.

But you can't take 100 vaccines into late-stage testing and then ultimately to manufacture them quickly to get the types of volumes we need.

Vaccine development typically takes years, and even with the unprecedented resources going into creating a COVID vaccine, things can only move so fast.

We're not going to have a vaccine the earliest till probably the third quarter of 2021, and even that would be a record time.

That's Dr. Peter Hotez, Dean of the National School of Tropical Medicine at Baylor College of Medicine, where his team is currently developing two vaccines against COVID.

This week on Epidemic, we're talking about vaccines in the era of COVID How are they developed? How safe are they? And once approved, what will it take to get a COVID vaccine to the American public and to the world?

When a disease appears, one wants to do everything they can to prevent it in the moment and to treat those who may have the disease to make it less severe. But of course, the best thing to do is to be able to have population immunity against the disease. And we've known this against terrible diseases like smallpox, polio, but also things like yellow fever where, you know, the capital in the United States in those days, Philadelphia in the 1700s, 10% of the population died. So when you vaccinate against them, you prevent them.

Seth and the vaccine alliance he leads, Gavi, are working to increase access to vaccines, especially in poorer countries.

So Gavi was started 20 years ago with the premise that there were new and powerful vaccines that the world had produced, but they weren't getting to the people who in some sense need them the most.

Since then, Gavi has helped get more than 760 million people vaccinated, preventing more than 13 million deaths.

And I say more importantly, we've introduced 433 new vaccines, vaccines like against diarrhea and pneumonia, the two largest killers of children, but also two cancer vaccines. So in a sense, we are really well set up to think about epidemic responses. We also keep the stockpiles for epidemic diseases, for cholera, yellow fever, meningitis, and now Ebola. And, you know, when a COVID vaccine is available, we will make sure to get it to to people who need it without any delay.

But before GAVI, governments, and other organizations can start to manufacture and distribute a vaccine, there needs to be a vaccine.

The process starts with understanding the immune response to a new disease because vaccines are designed to mimic this immune response minus the disease. We talked about the immune response in episode 23 last week. As a quick refresher, Long-lasting immunity is most often generated with the help of two branches of the body's immune system: antibodies and T cells.

Researchers are in the process of figuring out how each part of the immune response helps fight COVID.

My guess is, if looking at what I've seen so far, that most people who become infected with this virus will develop neutralizing antibodies and be protected at least for a while. I think T-cell responses are also important.

Now, in normal times, researchers would develop a more complete understanding of the immune response to an infection before moving into the next stage of vaccine development. But as we are all painfully aware, these are not normal times.

Given the pressure to end the pandemic, scientists are testing vaccines that mimic various parts of the response. This is happening at labs all over the world.

Testing so many different technologies and candidates, we'll be able to see, is there only one way to skin the cat, meaning you have to only induce neutralizing antibodies, or are there compensatory mechanisms that other vaccines can use to achieve a similar purpose?

So Farseth says it looks like a combination of neutralizing antibodies and T-cell responses will help combat COVID. Vaccines that do both will probably be the most effective. Government, university, and private industry labs have already moved several experimental vaccines into clinical trials.

The most talked about vaccine candidate is from Moderna Therapeutics. Their proposed vaccine moved from the lab in Cambridge, Massachusetts to human trials in a record-setting short period of just 63 days.

Moderna's vaccine utilizes messenger RNA—that's mRNA for short. mRNA is genetic code. It tells cells to manufacture proteins—in this case, a coronavirus protein. Scientists manufacture coronavirus mRNA and inject it directly into healthy cells. The cells start to make coronavirus proteins, and when the body sees those proteins, it mounts an immune response. An immune response without the infection, without the disease.

The Moderna mRNA vaccine moved into the second phase of clinical trials on May 25th. More than 600 volunteers will participate in this study.

The excitement, of course, is because you can make a piece of RNA very quickly, and so once you identify a new pathogen, the turnaround time for making mRNA and packaging it is pretty quick. So there's clearly an advantage there, and Moderna has been able to raise a lot of investor support on that idea, and it is worthwhile.

Worthwhile, but not a sure bet.

In the initial trial, 8 of the 45 participants developed a neutralizing antibody response. The company didn't release data related to the T-cell response. Peter's not ruling this one out, but he remains skeptical.

They haven't published a lot, just— they've published very little, in fact, and the little I've seen, I haven't seen whopping neutralizing antibody titers, and I haven't seen a lot of evidence of strong cytotoxic T lymphocyte production either. So on those two bases, I don't know that this particular technology is the one that's best suited for addressing COVID-19. And again, that's an opinion, that's not fact. We'll see if that's supported in Phase 2 and Phase 3 clinical trials.

Another approach uses a technology called adenovirus vectors, which are genetically engineered viruses. We've all been exposed to adenoviruses. They often cause a common cold. These adenovirus vectors are engineered to deliver a piece of COVID's genetic code into our cells, where just like with the mRNA vaccine, our cells start to manufacture COVID protein. And as with the mRNA vaccine, the body mounts an immune response against the COVID protein.

Adenovirus vaccines are designed to generate a combination of T-cell and antibody immune responses. Now, different versions of these vaccines have been in development for more than 30 years, but so far there isn't one that's proven effective in humans. That could change with COVID Labs at Oxford University in the UK and CanSino Biologies in China both have adenovirus vector vaccines for COVID in human trials.

Both of those in a single dose gave relatively low neutralizing antibody, but also gave good T-cell responses. So we'll see how that plays out and whether that could be modified, maybe adding another dose or through a prime boost, and, or maybe it'll work well as is. And again, we'll get a lot more information in the coming months as we see this, this stuff roll through clinical trials. So the point is we could get a very effective vaccine. I'm a little concerned that the program as it's currently configured is very heavily weighted towards new technologies. So I would like to see some additional types of technologies put in there, including some old school technologies.

This isn't just because Peter, an old-fashioned bow tie wearing guy, is stuck in the past. He thinks we need to hedge our bets. And proven old-school technologies need to be in the mix. Peter's in the process of developing two such vaccines in his lab at the Texas Children's Center for Vaccine Development at Baylor.

We develop the vaccines that usually the big pharma companies are not interested in, in working on because they're for poverty-related neglected parasitic infections. But a decade ago, we teamed up with a group at the New York Blood Center that had a very compelling idea to make vaccines for coronaviruses. And we made several vaccines, including one that was manufactured against the SARS coronavirus. But unfortunately, we could never raise another round of funding after that to move it into clinical trials, because by the time we had made it, nobody cared about coronaviruses anymore. And that's the way it stood for years until suddenly in January, Suddenly, for some reason, people were getting interested in coronavirus vaccines again, and we realized that ours was close enough that we could also develop it as a vaccine for COVID-19.

And for the past 3 months, that's exactly what they've been doing.

We've started to engage the Food and Drug Administration, the FDA, and hopefully in the coming months we'll have the green light to move forward into clinical trials.

Now they're in the process of developing a second vaccine as well. While Peter is hopeful, he says it's still too soon to say whether either will be the answer.

As his lab and others continue to learn more about COVID there's a chance that we'll realize there is no front-runner.

If all the stars align and everything works, we may have multiple vaccines, and different vaccines may have different indications. Some may work better in older individuals. Some may work better with those underlying comorbid conditions. Some might work better for younger individuals. I don't think we're going to see a one-size-fits-all vaccine, because if you look at the cohort of adults that need to be vaccinated, you're talking about 4— more than 4 billion adults. It's going to be really hard to scale up one vaccine to that level.

Regardless of which comes out first and which proves most effective, the goal of each vaccine is the same.

It's supposed to protect you so that if you get exposed to the virus, you won't get severely ill and require hospitalization or go into the intensive care unit. That's one. And the other is that if enough Americans take it, it should be able to interrupt transmission of the virus.

But for a vaccine to interrupt transmission in a population, it needs to lead to something called herd immunity.

It's a concept that once enough people are immune, either because they had the virus and they've naturally developed immunity or because they were vaccinated, a virus has less opportunity to spread and so it starts to die out.

This is how we've essentially beaten polio without eradicating the virus completely. Here's Seth Berkley again.

Herd immunity depends upon the, the particular agent. So for example, for measles, which is the most infectious agent, much more infectious than say SARS-CoV-2 virus, measles, you need 90 to 95% of the population to be immune to get herd immunity. Haemophilus influenzae type B, which is a form of pneumonia, you only need about 70% of the population to be immune before you begin to see herd immunity. So we don't yet know in coronaviruses what that number will be. I suspect it's going to be on the higher side given the infections we've seen, but not as bad as measles. So maybe, you know, something like 80%.

But to achieve herd immunity, you need something else. You need almost all the people to agree to take the vaccine, and you can't take it for granted that they will.

Vaccine introduction is a tricky thing. It's not easy to get vaccines accepted by countries in general, and there's a whole science behind vaccine introduction that great organizations like GAVI and the WHO and the Gates Foundation have been fine-tuning for years, and it's a particular problem in the U.S. The anti-vaxxers.

Anti-vaxxers believe that vaccines cause more problems than they prevent. They allege, for example, that vaccines cause autism in some children, even though numerous peer-reviewed scientific studies have shown vaccines to be safe and effective.

Peter knows this crowd well.

You're right, I've been sort of public enemy number one with the anti-vaccine movement for a while.

Peter is the author of a powerful memoir entitled Vaccines Did Not Cause Rachel's Autism. The book tells the story of his adult daughter who is on the autism spectrum. Peter wrote the book to try to persuade people that vaccines are necessary and safe.

The anti-vaxxer movement has had serious consequences. Peter points to the case of the vaccine for human papillomavirus, also known as HPV. Some strains of HPV cause cervical cancer, other genital cancers, and throat cancer. Vaccinating boys and girls for HPV could eliminate HPV-related cancers. Unfortunately, that's not happening in the U.S.

We have one of the very low uptake rates in, in the world, uh, compared to Australia, which has announced they're going to eliminate cervical cancer by the year of 2030. We're doing the opposite because resistance has been so strong to vaccine introduction.

And this resistance has come at a tremendous cost.

We are condemning a generation of girls and women to cervical cancer, and those same forces are going to be in place with, with COVID-19. So, you know, there's no room for error in terms of mis-messaging or conflicts of interest or even the perceived conflicts of interest.

Regrettably, some of that mis-messaging is already out there.

We've had some of the biotechs and pharma companies sending out outrageous press releases saying we're going to have the vaccine in weeks and months, and that's absolutely not true, and that's been feeding into it. We have the White House calling this Operation Warp Speed, using the Star Trek metaphor, and, and that's played into it.

It's the last thing we need in the midst of a pandemic.

It's actually reinvigorating the anti-vaccine lobby, which is the last thing I thought would happen. You would think, you know, with many Americans clamoring for a COVID-19 vaccine, this finally— I thought the anti-vaccine movement would go into retreat or, or in hiding, and they did for a few weeks, and then they've now been re-energized because of all the missteps. It's compounding the issue.

The challenge in all of this is that we need to have people understand science and trust science. Seth Berkley again. We've ended up in a world where people have lost trust to science, lost trust to authorities, and that's a real problem as we see in this particular circumstance where, you know, people are using all kinds of of treatments and doing things that aren't scientifically validated and putting themselves at risk.

There might be one silver lining in all of this.

A silver lining that could disarm the anti-vaxxers, at least in the case of COVID One of the reasons vaccine hesitancy has occurred in the developed world is because they've been so successful that these diseases are not visible anymore and people have forgotten how bad they are. I wonder, given how bad this epidemic is, Will people now embrace vaccines in a different way? And I think, you know, time will tell on that. But my hope would be that when science does come up with a vaccine, because I certainly believe it will, that this will be something that's seen as a savior to many people and that it will be embraced around the world.

It's scary to think about a strong anti-vaxxer response to COVID. And yet it's already starting. An Associated Press poll released on May 27th found that 20% of Americans would not take a vaccine against COVID. Another 31% were unsure.

That's more than half the population, and if that's what actually happens when the vaccine arrives, we will be unable to achieve herd immunity.

We need a lot of Americans to take the vaccine in order to achieve herd immunity, so the two goals of vaccination is one, to prevent people from getting sick, but also hopefully, if enough Americans take it, to interrupt transmission of the virus, provided you reach a certain level, just like we've done for measles. And I'm worried now that second indication may not happen because of all of this. So we've got to do a lot of damage control.

And here, Peter is again taking the lead.

I've been speaking with the leadership at the NIH and White House, and to at least let's, let's do some damage control and let's put in place a communications plan for the vaccine program because there's so much misunderstanding out there right now.

What's so frustrating is that so much of this misunderstanding is coming from the White House. We're seeing the president of the United States advocating for some of these risky treatments.

This White House in particular seems to gravitate towards magic solutions. First it was hydroxychloroquine, then it was remdesivir. Now it's the vaccine, and it's really important to point out there are multiple vaccines. This is not a magic solution. The vaccine will be adequately tested for safety, will be adequately tested to show that it actually works. It'll take at least a year, and we use that time because we need to accumulate enough data showing that the vaccine works and it's safe, and that takes time. There's no way to rush it. I think oftentimes what we're seeing is the White House views this the way they, at least in their public messaging, the way the vice president and the president explain it, as though it's a manufacturing issue. You know, we're scaling up to make ventilators, we're scaling up to make diagnostic kits, we're going to scale up to make vaccines, but it's not the same. Manufacturing is a key step, but it's ultimately the real rate-limiting step is showing that it actually works and it's safe and explaining that we're not rushing things What we're doing is all the things around it, doing, doing the manufacturing at risk, getting multiple candidates out there. That's how we're accelerating timelines, not sacrificing safety.

It's complicated and it takes time.

I mean, the good news is America ordinarily knows how to do this. You know, we have all of these belts and suspenders and infrastructure in place to help with the rollout of vaccines.

That's certainly the hope, and Seth's team will be instrumental in seeing that hope realized.

When a COVID vaccine is available, we will make sure to get it to people who need it without any delay.

Gavi is holding its Global Vaccine Summit on June 4th, during which countries from around the world will announce their pledges to support Gavi's core programs from 2021 to 2025. The goal is to raise $7.4 $44 billion, and that appears to be on track.

One of the first matters of business is figuring out how to make sure that the vaccine that scientists developed can be administered around the world. That starts with manufacturing.

Some vaccines are easier to produce, some are harder to produce, and that will be part of the criteria when one chooses a set of promising vaccines. Ideally, you want them to be ones we know how to produce and produce at scale.

Once a vaccine gets the green light, it still needs to be manufactured in very large numbers, not just for the U.S., but for the entire world, and that's a big challenge.

In terms of thinking about that production, the way you try to do it is to get all of the manufacturing facilities in the world ready to go. Now it's important, though, that you do not stop them from producing vaccines that are currently being used in saving lives. So what you're looking really for is excess capacity. And this effort is going on right now. There's a group that's gotten together to look at manufacturing across the world. I think the answer is going to be there will be substantial capacity to do that. But that's why you have to have a global perspective, because if you're any one country or one area and you're only thinking about what you have in your country, that's going to be a real problem. And there are actually whole continents that don't have manufacturing capability. So what we're going to rely on there is having a global view of it with multiple manufacturers working on it.

And then there's the question of actually distributing it.

There will be always a limit to the number of doses when they first come out. So what you need is a really good allocation mechanism on how those should be used and where they should go.

Funding all of this is no small matter either.

There are two ways to think about it. One, you again can think about it You know, nationally, company by company. And if you do that, I think you have a real challenge because you won't get the best products. And instead, in a global emergency like this, I think what we really have to think about is a global public good mindset. And the argument there would be that this product will stop the epidemic for the whole world, not just for any individual country.

A vaccine program at a global scale can't be done with governments and NGOs alone. It has to include private industry too.

You could get the companies to come together and say they would work together to share the tools because it isn't just the vaccine. It may be things like adjuvants, which are chemicals you put into vaccines to make them, you know, have a stronger immune response, as well as being able to fill and finish the vaccine, label the vaccine, etc., which are all parts of what needs to happen. So that would require a global consensus already. The G20 has begun to discuss this as a potential possibility, but whether we will be able to get there, I don't know, but that is certainly what I would advocate for.

Right now, everyone is trying to get a vaccine. We're seeing promising studies out of the UK, China, and the US, but we can't get ahead of ourselves. The scientific process is used for a reason, and it needs to be completed.

It may be that we'll see several vaccine, partially protective vaccines roll out first, They may not be optimal, but they'll greatly reduce severity of disease in this country and prevent deaths, which is so important, obviously. And, and then over time, they may be refined. We may increase the number of doses. We may combine them with different vaccines in innovative ways. So the point is, this is not a one-and-done thing. This is going to take years to fine-tune, but at least we'll get a couple of vaccines out there, hopefully by by the end of next year.

Even as we continue to develop our understanding of this coronavirus, scientists are already looking at the next one.

It's evolutionarily certain we're going to have more of them, and so we should be doing research in peacetime on these agents. One last point, there are 30,000 coronaviruses in the database of coronaviruses, and we should be looking at which ones are likely to jump, and that's only coronaviruses.

Peacetime research, as in research conducted while we're not waging global war against a pandemic. Peacetime research in hopes of avoiding that next pandemic before it has a chance to wreak the havoc we've seen with COVID Bill Gates and I did back-to-back TED Talks 5 years ago.

He talked about this certainty of having further outbreaks, talked about a respiratory pathogen, and kind of laid out what the scenario we're in right now, which people have, have kind of said is, you know, made him a clairvoyant on this. My follow-up talk was about how we could prepare vaccines for this situation, and I suggested two things. On the one side, we could have an organization that could begin to make vaccines against a broad range of potentially known threats.

This led to the creation of CEPI, the Coalition for Epidemic Preparedness and Innovation, They've begun their work on a list of known potential threats, but even that hard job isn't enough.

There is this concept of disease X, and disease X would be the unknown disease. Now, there's a way to deal with that as well, and that is to create what we would call platform technologies. And those would be, you know, vaccines that would be well worked through, understanding how to scale up, how to manufacture, and And when you had a new organism, you would then be able to put it in that platform and you could move it more quickly through. It's a little like flu vaccines. Every year we get new strains of flu. We put them in the flu backbone. We don't go back to phase 1, phase 2. We just have to make sure that those vaccines are stable and pure and they can move forward fairly quickly. That type of process, and you'd need a range of those, platform vectors for different types of agents would be a way to prepare for the future.

A future we're all looking forward to, for it offers at the very least an end to this pandemic.

And now a personal note. In late February, when Celine and I launched this podcast, there had been only one identified death due to coronavirus in the U.S., just one. But even that first episode I said, We cannot build a wall to keep this disease out. We have to understand it's here already, and it's going to come to a greater extent, and we need to be acting now to prepare to deal with that. 3 months later, more than 100,000 Americans are dead. More than 40 million are out of work. The consequences continue to mount. The questions this podcast asks and the answers we try to provide are far from done. But after nearly 30 episodes and well over a million downloads of Epidemic, other duties call. And so I'm going to be stepping aside as Celine's co-host. You'll hear me on future episodes helping out with some interviews, and I'll be back from time to time as a guest. But by and large, Epidemic will continue on without me. I'm grateful to the outstanding experts and activists who joined us to illuminate this unfolding crisis. I've learned I've learned so much by talking to them. I'm grateful to our producer, Zach Dyer, who's done a fantastic job making our work better. And of course, I'm grateful to Celine, who never ceases to impress me with her incredible expertise, her boundless enthusiasm, her tireless determination, and her generous spirit. But mostly, I'm grateful to all of you who've listened, suggested topics, and offered ways for us to improve. Thank you. And for all of you, our listeners, I want to close with this thought. From time to time, listeners complain that this podcast is too political. We've been critical of the federal response, outspoken on how the needs of particular communities have been ignored, unflinching in connecting the path of the epidemic to other social problems. So let me say this: for any mistakes I've made or names I've mispronounced, I apologize. But for seeing the inexorable link between the path of a pandemic and public policy and social issues, I offer no regrets. The coronavirus is a natural phenomenon explained by science, but nothing about its impact— who it's made sick, who has recovered, how we've handled the response, what communities it has devastated, what consequences it has had and will have— are the direct result of nature. Rather, They are due to the society the virus has encountered and the choices we have made in response. Doctors, nurses, and researchers beat diseases, but policy, people, and public health beat pandemics. The choices we all make as a country decides who gets medical care and how, who gets medicines and vaccines and when, who is spared the disease because someone wears a mask or practices distancing or gets a test on time, and who gets the disease because others don't. The goal of this podcast is to try to help all of us make better choices. Thanks for giving me this platform to advance that objective, and I hope you will all continue to be actively engaged in making the changes needed to do better in this life and death struggle. And please keep listening to Epidemic.

Ron, I want to thank you for an incredible experience working together on this show. Thank you again for helping us launch Epidemic and for your ongoing support. We look forward to having you back from time to time in the future. Epidemic is brought to you by Just Human Productions. Were funded in part by listeners like you, were powered and distributed by Simplecast. Today's episode was produced by Zach Dyer, Danielle Elliott, and me. Our music is by the Blue Dot Sessions. Our interns are Sonia Baradwa, Annabel Chen, Isabel Ricci, Claire Halverson, and Julie Levy. If you enjoy the show, please tell a friend about it today. And if you haven't already done so, leave us a review on Apple Podcasts. It helps more people find out about the show. You can learn more about this podcast, how to engage with us on social media, and how to support the podcast at epidemic.fm. That's epidemic.fm. Just Human Productions is a 501(c)(3) nonprofit organization, so your donations to support our podcasts are tax deductible. Go to epidemic.fm to make a donation. We release Epidemic twice a week on Tuesdays and Fridays. But producing a podcast costs money. We've got to pay our staff. So please make a donation to help us keep this going. And check out our sister podcast, American Diagnosis. You can find it wherever you listen to podcasts or at americandiagnosis.fm. On American Diagnosis, we cover some of the biggest public health challenges affecting the nation today. In Season 1, we covered youth and mental health. In Season 2, the opioid overdose crisis. And in Season 3, gun violence in America. I'm Dr. Celine Gounder. And I'm Ron Klain.

Thanks for listening to Epidemic.