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From the Front Row: Clinical trials, COVID-19 vaccines, and what comes next

Published on February 25, 2021

The following is a transcript of an episode of From the Front Row: Student Voices in Public Health, the University of Iowa College of Public Health’s student podcast. This week, Alex hosts a terrific and timely interview with Dr. Patricia Winokur from the University of Iowa. They talk about the development and clinical trials process of two types of COVID-19 vaccines and the part that Dr. Winokur and the UI played, and is currently playing, in studying the effectiveness of these vaccines.

As an infectious disease specialist for the University of Iowa Hospitals and Clinics, Dr. Winokur is the principal investigator for the UI trial of the new COVID-19 vaccine made by Novavax and led the UI site clinical trial for the Pfizer and BioNTech vaccine.

Alex Murra:

Hello, everyone. Welcome back to From the Front Row, brought to you by the University of Iowa, College of Public Health. My name is Alex Murra, and if this is your first time with us, welcome. We’re a student run podcast that talks about the major issues in public health and how they are relevant to anyone both in and out of the field of public health. Today we will be chatting with Dr. Patricia Winokur, who is the executive dean for the University of Iowa Carver College of Medicine, and a professor in the Department of Internal Medicine. As an infectious disease specialist for the University of Iowa Hospitals and Clinics, Dr. Winokur is the principal investigator for the UI trial of the new COVID-19 vaccine made by Novavax, and led the UI site clinical trial for the Pfizer and BioNTech vaccine.

Alex Murra:

She earned her MD from Washington University School of Medicine in St. Louis, and completed her internal medicine residency from the University of Iowa. Today, she is here with us to discuss the current COVID-19 vaccine trials and their implications for the future. Welcome to the show, Dr. Winokur.

Patricia Winokur:

Thanks Alex, it’s really a timely podcast. There’s lots going on in the vaccine world with COVID-19, so glad to be here.

Alex Murra:

To start us off, can you tell us about the COVID 19 vaccines that are starting to become available? Although each of the vaccines offers immunity against the virus, how are the vaccine technologies different?

Patricia Winokur:

Well, I think the way I look at it is let’s start with how they’re the same. And when you think about the COVID-19 vaccines that have been created, the vast majority, especially those in the United States, are all targeting spike protein, which is this major protein that sits on the outside of the SARS Coronavirus that causes COVID-19. So they’re all targeting the same protein. Where they differ then, is how that protein gets exposed to the human immune system. And the most recent strategies for getting the spike protein exposed and the ones that have actually been in the emergency use authorized vaccines, the ones that were first out of the gate, are ones where your human body and the cells in the body actually make the protein.

Patricia Winokur:

So the vaccine is essentially delivering the blueprints to the human cell and then the human cell is making those proteins and exposing them to the immune system. More traditional vaccines, and these are some of the ones that are coming up now, like the Novavax vaccine, are using a manufacturing plant to make the spike protein. And then when they inject it, they are injecting a pre-formed spike protein. So it’s a little different in how the body gets exposed to the spike protein, but they’re all kind of doing the same thing just in slightly different ways.

Alex Murra:

Yeah, that’s good to hear. I think sometimes people are hearing that the Pfizer vaccine is an mRNA, and I think the confusion comes from all it’s doing is just giving yourselves that code to really make the protein. And in a way it’s not too much different, because after that protein is made your body and your immune system attacks it the same way.

Patricia Winokur:

That is exactly correct.

Alex Murra:

Yes. So getting on to how the vaccines are really developed and how they’re tested. Last fall you had helped lead the clinical trial, the Pfizer vaccine, at the University of Iowa hospitals and clinics, and now you are helping to lead with Novavax vaccine. So what exactly does the clinical trial process entail? And really if we know that the Pfizer and the Moderna vaccines are working, since they’re being put into the population, why is it important to do a clinical trial on another vaccine?

Patricia Winokur:

So this is another way that you look at how the trials are similar and how they’re different. And when we do clinical trials, there’s a very set way that we start to evaluate a new vaccine or any new drug. And all of that work starts in the test tube in the basic science labs, trying to understand what proteins are most important for creating that immune response that’s protective. Then they go into animal studies where they’re looking at safety, and then they go from animal studies into very small numbers of humans, again, really focusing on safety, but then starting to evolve the best dose of a vaccine and eventually get to these large studies. And remember, the studies that we’re doing now for COVID-19 are huge. They’re usually 30,000 people per study.

Patricia Winokur:

The other thing that we have to do, and we’re looking at clinical trials, is we need to develop them in a way that we’re really answering the right question. And for COVID-19 that right question is, are these vaccines preventing people from getting infections? And so all of the studies now are designed in a pretty similar way, which is trying to answer that question. And most of them are studying a half the people are getting what we call placebo and half the people are getting active vaccine, and then they’re comparing the rates of acquiring COVID-19 infection. So they’re very similar in that way. I think as you start to go into the new clinical trials, as we’re starting to evolve, we may have to change that strategy. And typically what you would do as you get later into the drug stories, you just start comparing one vaccine to another, and it’s not ethical any longer to use a placebo. We’re not quite there yet. The FDA right now is still asking for a placebo controlled trial, so that’s what we’ve been working with so far.

Transcript continues below photo

Jaelyn Pulkrabek, 4th year Pharmacy student administers the Moderna Covid-19 Vaccination at the Medical Education Research Facility (MERF) to College of Medicine and College of Nursing students

Alex Murra:

A follow-up question to the clinical trial vaccine process is, some people you can hear on social media and within the news, they’re asking if this process has been rushed. Because we’ve seen unprecedented speed with the vaccine being developed and now within almost like a year it’s being distributed. So do you have any comments on that? Was the trial compromise in any way because of the speed that it’s been done?

Patricia Winokur:

So this is a really important question because I do think that operation works speed title, it certainly got us all activated and got things going fast, but it also created that anxiety that perhaps things were rushed. And I think this is where you go back. Remember I said at the beginning that all trials start with trying to understand what’s going on in the test too, and in animal studies. And we were lucky in the sense that we had some previous experience with two other corona viruses that we were really worried about. And the first was in the early two thousands, there was an infection called SARS. It was the first severe acute respiratory syndrome. It was a Coronavirus, very much like the virus that causes COVID-19. It spread in a few countries and we were really worried that this was going to turn into a pandemic. So the scientists got busy. They started figuring out what was important in that original SARS Coronavirus that caused the immune system to develop a protective response.

Patricia Winokur:

Then in around 2012, there was another Coronavirus. This one was very much a respiratory virus, caused a pretty severe illness. It was transmitted from person to person. It was in the middle East, and it was pretty much located in countries in the middle East. That was called the Middle East respiratory syndrome Coronavirus. Again, we were pretty worried about that infection and that, that could become a pandemic. And so the scientists started looking at that Coronavirus, and they started comparing their original SARS to the MERS coronavirus. Again, starting to develop that understanding of what was most important. And actually both of those viruses use the spike protein as their major, what we call immunodominant protein. They got into animal studies and they developed a vaccine.

Patricia Winokur:

They never ended up using those vaccines in humans because both of those infections kind of petered out, fortunately. Well now we have a Coronavirus that has so many similarities to SARS and MERS. We learned so much about the science of those two viruses. We had animal studies that were looking at these very similar Corona viruses, and we had vaccine data from those animals. So we could actually get to the kind of meat of creating a vaccine much more quickly. And we also have new vaccine platforms that we’ve been working on for 15 to 20 years. So a lot of this wasn’t rushed. We went through all the stages of investigating small numbers of humans to understand safety and following them very closely looking at all their signs and symptoms with the vaccine and honing in on the right dose. So I don’t think it was as rushed as it sounds like. And that was because of all the science that was done with these previous infections.

Alex Murra:

That’s really good to hear. I think that’ll be really reassuring for people to start to hear the history of how this vaccine has been developed. You had touched on this a little bit earlier, but a little bit on the effectiveness on the vaccines. Almost every day you can turn on the news and you hear these news reporters throwing out these statistics. They’re saying that a vaccine is like 95% effective or 65% effective. In the context of vaccine effectiveness and research, what does it really mean? You had said before that these trials are designed as to whether or not they prevent illness, should we be focusing on preventing illness or preventing the severe outcomes of COVID?

Patricia Winokur:

Well, I think that both of them are really important. And what does it mean when it says that a vaccine is 95% effective? And I think the way you can look at that, the Pfizer vaccine was the first out of the gate. And what we learned was if you looked at the placebo group, and this was the group that got salt water, they ended up seeing about 169 cases of symptomatic COVID-19. And then you looked at the 15,000 people that had the active vaccine, and there were only nine cases. So 169 cases occurred in the group that got salt water, and nine cases occurred in those without an active vaccine. That’s when you do the statistics, it shows that 95% of people that got the coronavirus vaccine were protected. Now, they looked at simply symptomatic infection. It could be mild, it could be moderate, or it could be severe.

Patricia Winokur:

Now we have some of the new vaccines that are starting to have their data being analyzed. And this is AstraZeneca in the European Union, this is Johnson and Johnson in the United States. And you heard that their efficacy was less impressive. 72% for the Johnson and Johnson. Well, 72% has a lot better than none. It isn’t as good as 95%, but really what are we trying to do when you think about trying to really quell this pandemic? There are two things. One is we want to stop spread, BUt we also need to protect our hospitals and all the resources that are needed to care for the most severely ill individuals. If you look at the Johnson and Johnson data, yes, they analyzed the ability to protect against symptomatic disease that could be mild, moderate, or severe, but you can also look at it to see did it prevent hospitalizations in severe disease.

Patricia Winokur:

And when you looked at it that way, it was 85% effective. So that’s where you’re starting to see, yeah, it isn’t quite as good as 95% effective at any type of symptom, but it sure would be helpful to prevent hospitalizations, ICU use, death. And so it doesn’t mean that it isn’t a good vaccine. And I think we all got a little spoiled, to be honest. I thought that all in all I was actually expecting this vaccine to be closer to 70% effective. I thought it was going to be a little more like flu. And when we saw that early data that it was 95% effective, I mean, we’re all jumping for joy. But 70% effective is really good too.

Alex Murra:

Yes, I definitely agree. I know that when I get the chance to take one of the vaccines, I will be very happy to take any of them at this point.

Patricia Winokur:

And I think another thing is that it probably is going to also impact the spread of disease. We don’t know that for sure yet, but I think the likelihood is when we get that data, it’s going to show that these vaccines do reduce spread from person to person.

Alex Murra:

Yes, I’m looking forward to reading those reports when they come out. And now with the effectiveness of the vaccines, we know that they have been tested against the strains that we have seen previously, but we’re seeing new variants of COVID popping up. Notably, we have the UK, the Brazilian and the South African variants. And a lot of the researchers going into these variants have shown that there may or may not be be better at evading the immune responses, and they might be more infectious. Given these new variants, do you think that the current vaccines are going to be effective? And if they aren’t, how are we going to move forward?

Patricia Winokur:

So I think we’re starting to get some of that data. And this is where some of the new vaccines like Johnson and Johnson had some natural experiments going on. So they were running their trial, not only in the United States, but also in Brazil and also in South America or South Africa. And in some of these other countries, some of the variants were starting to rise. So we had the natural experiment going on because of timing. I think the vaccines are going to show some reduction in efficacy, but it’s not going to be completely reduced. And so this is a good thing in the sense that it is probably going to have the greatest impact on severe disease. We may still see more breakthrough of symptomatic COVID-19, but we’re going to see less of the severe disease. So I think the vaccines are still good, but we need to figure out strategies to make them more effective against these variants.

Patricia Winokur:

And that work is going on today. And this is where we’re looking at the test tube, we’re going back and we’re taking all the blood that we had from some of those that got the original vaccines, we’re testing it in the test tube against some of these new variants trying to learn. But we’re also starting to develop new variations of the vaccine. And there are several ways that we may end up trying to combine different strains in one vaccine. So maybe you would take half of that vaccine and have one variant, and the other half have the other variant so that when you inject it, your body is seeing both variants and making antibodies that are appropriate. Or you might see that you start with one vaccine variant and then you boost with another. And then you’re again, developing an immune response that covers both types of COVID viruses that are circulating. So we’re going to end up learning that that data is still early, and we’re starting to understand how the best strategies for creating these multivalent vaccines will best protect people.

Alex Murra:

That’s interesting. I think about it looking almost like the flu vaccines that we get every year with all those multiple strains of the flu. Especially since there’s talk that COVID is likely to become endemic. There’s a very real chance that it will be. So it’ll be interesting to see if this becomes a new yearly vaccine for us to get.

Patricia Winokur:

And I think that’s true. I think flu is an excellent way of looking at it. The other thing that’s really good is these messenger RNA vaccines, and some of these new types of vaccines can be modified very quickly. And the other thing that’s going on in the background is FDA is working with the companies to try and understand the way that they would approve the next batch of vaccines. Would you have to go back and do a 30,000 person trial? And what I’ve heard through the Grapevine is the answer is no. That they’re going to allow us smaller studies and different ways of proving that these new variations of the vaccine are able to be licensed in the United States. So that part’s really good. So there’s a lot of different things that need to happen at the same time that will bring us these new vaccines that we’ll need.

Alex Murra:

Vaccine news is ever changing and it’s so rapidly changing. Sometimes it’s hard to keep up with. One of the things, well, now we’re talking about news is again, we start seeing these things about the side effects, these reports the side effects of the vaccines. So some people are reporting flu like symptoms or soreness at the injection site after either dose one or dose two. And why would the vaccine, if it’s supposed to prevent illness, why is it going to make people feel ill at the same time?

Patricia Winokur:

Well, so when you stimulate the immune system, the immune system makes chemicals. And these chemicals help your immune system evolved to make the antibodies that are protective, but those chemicals can cause a little bit of a reaction in the body too. And those chemicals can cause that fatigue and a low grade temp and just that achy feeling. So it’s not a bad thing to have those symptoms develop. It means your immune system is revving up, so to speak. So it’s not unexpected. I think this vaccine is a little bit more reactive than some others. And I think that maybe the spike protein that as you’re making an immune system to that spike protein, it may be a pretty good immune stimulant, let’s put it that way.

Alex Murra:

Do you know if there are any recommendations? Like, can you take Tylenol after you take the vaccine to try and curb those symptoms then?

Patricia Winokur:

So people can take Tylenol or ibuprofen to help with the symptoms. I prefer that they don’t take them before they go to get their vaccine. That we do know can reduce the immune response just a little bit, not a lot. So if you made a mistake and took some Tylenol because you had headache or something, you’re okay. But in general, I ask people to wait. And then when they develop the symptoms, take some Tylenol and that’ll help. It does make the symptoms much better. And it’ll get you through that 24 to 48 hours where you feel just a little under the weather.

Alex Murra:

So now we’re starting to see data with an equitable vaccine distribution. As the vaccine is coming out, people across the country who might need the vaccine are not getting it. They don’t have access to it. How are decisions being made as to who has the access to vaccination and when? And as we start to see different groups be vaccinated, when will be began to see the impact of the pandemic start to go down?

Patricia Winokur:

So the United States has a couple of different strategies for deciding who and how gets vaccine. Now, some of it is being managed at the national level, and this is through CDC and some of their committees that recommend the strategies. They’re doing a lot of the modeling, trying to understand who is most at risk, and also who’s the biggest spreader. And those are often two different groups. They make some general recommendations, but then the actual implementation of those strategies is being done state by state. And I think that’s been difficult because you do see different states using different strategies. That’s been hard because we don’t have enough vaccine and to see perhaps your family members in one state getting access, you’re not getting it at your own state, that’s been a really difficult situation.

Patricia Winokur:

But we are starting to get more vaccine delivered. We’re starting to develop better systems, I think in each state to deliver the vaccine. And you can see different strategies all over the country too. Some are doing drive-through vaccines at Dodgers Stadium. Others are doing it at the local pharmacies. As we’re starting to get these different strategies, I think we’re reaching out to different people. But we have to be really careful because there are individuals that don’t have access to computers. They don’t have as much time to find an appointment to get a vaccine. And so the public health departments really are very much trying to figure out strategies to ensure that certain communities are getting access to the vaccine. And that’s really important because some of these communities have been greatly affected.

Alex Murra:

And kind of going off of that as well, there are people who are still hesitant and reluctant to take this vaccine. Despite all the evidence that’s out there, unfortunately, we have these anti-vax movements. What roles can public health and medical professionals play in establishing effective education campaigns for people who are nervous or reluctant about getting the vaccine? And how can we ensure that these messages are reaching everyone?

Patricia Winokur:

So I think the community strategies that the public health departments are using are very effective. I think learning about vaccines and understanding the effects comes much better from someone that you know and trust. So reaching out to trusted community members and working with them to understand what are the side effects? What are the real facts behind this? And having them be the spokesperson is often much more effective than having someone even like the governor or someone at the CDC or the public health department. They’re all really important, but then getting that information into a format that is more grassroots is helpful.

Patricia Winokur:

The thing I’m happy to see as I’ve been watching this, more people who are hesitant at the beginning are now understanding the safety and they’re willing to get it. And I think a lot of it is that kind of person to person communication as much as anything. And so that’s her job, is to get that information out to all sorts of different people and give them the facts, make sure we’re delivering the information in the right language. Maybe a community has English as a second language and we can get that information out in a different way that helps them feel comfortable.

Alex Murra:

Yeah, it’ll be really exciting to see how we can use different forms of media and different types of communication to really get that message out there. And also one of the things I think has been nice to see in this pandemic is some sense of effort to come together and try and work through everything and hopefully move on. One of the last questions that we like to ask all of our guests that come onto the podcast is what is one thing that you thought you knew but were later wrong about?

Patricia Winokur:

So I alluded to it, I really thought this vaccine was going to be a little less effective. I thought it was going to be closer to 70% effective. I also thought that we would see what we’ve seen with most vaccines, which is the 65 and over crowd would have a less impressive immune response. We’ve been lucky. When we’ve looked at these vaccines, their antibody responses might be a little bit less, but the protection against a symptomatic disease has been really good in the elderly. And that’s very helpful since they’ve been so disproportionately affected the severe disease.

Alex Murra:

Yeah, that’s very interesting. I think that with this virus in particular, it’s been, in a way, similar to viruses that we’ve seen in the past, but it’s been very different. And just the whole process, it’s going to be a great learning example. I know that we will all continue to learn from this virus for many years to come. I wanted to thank you, Dr. Winokur, for taking the time to talk with us. I think it was a really interesting conversation to have, and that lots of people hopefully will benefit from hearing all of your expertise on the vaccine. So thank you for coming on to talk with me today.

Patricia Winokur:

Thank you so much.

Steve Sonnier:

That’s it for episode this week. Big thanks to Dr. Patricia Winokur for coming on with us today. This episode was hosted, written, edited, and produced by Alex Murra. You can find more about the University of Iowa, College of Public Health on Facebook. Our podcast is available on Spotify, Apple podcasts, and SoundCloud. If you enjoyed this episode, please share it with your colleagues. Our team can be reached at cph-gradambassador@uiowa.edu. This episode is brought to you by the University of Iowa College of Public Health. Keep on keeping on out there.