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A new episode of our podcast, “Show Me the Science,” has been posted. At present, these podcast episodes are highlighting research and patient care on the Washington University Medical Campus as our scientists and clinicians confront the COVID-19 pandemic.

It’s been a busy summer in the laboratory of Ali Ellebedy, PhD, an associate professor of pathology & immunology and of molecular microbiology at Washington University School of Medicine in St. Louis. Studying samples from patients with COVID-19 infections and others who have been vaccinated against the virus, he’s found hopeful signs in the immune system — even regarding the vaccine’s response to the highly infectious delta variant. His laboratory has reported that the immune system continues to make protective antibodies for many months after both natural infection and vaccination, but he says that as long as anyone on the planet is infected with COVID-19, the rest of the world can’t be fully protected. As his research continues to show that vaccines are effective at preventing severe disease, Ellebedy says it’s important to increase access to vaccines and to encourage people to get vaccinated. The current vaccines are effective at protecting the vaccinated from severe disease in the lungs, but to eliminate most  breakthrough infections, Ellebedy says it may be important to develop vaccines that better protect tissues in the nose and throat.

The podcast, “Show Me the Science,” is produced by the Office of Medical Public Affairs at Washington University School of Medicine in St. Louis.

Transcript

Jim Dryden (host): Hello and welcome to “Show Me the Science,” conversations about science and health with the people of Washington University School of Medicine in St. Louis, Missouri … the Show-Me State. As we continue to detail Washington University’s response to the COVID-19 pandemic, we look in this episode at some good news that has appeared in the midst of the bad news involving the delta variant. New research from the laboratory of Washington University’s Ali Ellebedy has shown that the delta variant of the coronavirus is not particularly good at evading the antibodies created by vaccination.

Ali Ellebedy, PhD: Breakthrough infections are not really a failure. The goal of the vaccine is not really to prevent infection. The goal of the vaccine is to prevent severe disease and prevent death. And from that perspective, vaccines are working very efficiently.

Dryden: Ellebedy, a researcher in the Departments of Pathology & Immunology and of Molecular Microbiology, has had a busy few months publishing papers that demonstrate that vaccines and natural infections with the SARS-CoV-2 virus produce antibodies that remain in the system and provide pretty good protection against future infections. He says there are many reasons for the surge in cases that’s been seen over the course of the summer.

Ellebedy: One of the things that we are learning — actually, we all should know that not all vaccinated people are the same. And the same thing for all infected: Not all infected people are the same. If we randomly take 100 people from the street and give them the same vaccine, their responses will be all over the place. And that’s natural. And that’s normal. It remains a problem that we have a significant proportion of the society that’s really not vaccinated, and that gives ground for the virus to still propagate, to multiply, to even — as we are seeing now, the virus itself changes and becomes more infectious. That allows the virus now to come back. And even for people who have been partially protected because of immunization, now they are more vulnerable because the virus itself changes. I think we should always remember that as long as there is someone on this planet that hasn’t been immunized or infected, the virus will never go away. The other part that we really don’t have to even go outside of there is our children. I have three children, and I am very concerned. I’m hoping that with all the precautions being taken in the school and hoping that everyone, every adult in the school, hopefully, had a chance or been offered the vaccine. But still, this is where, really, our — I would think this is our front line now. This is the population who have a very established history of being able to transmit freely respiratory viruses. And this is a population that we are now putting into large groups, completely unimmunized, no prior immunity. We are already seeing some signs of school closures and a lot of things that — but this is where, I think, we could use the vaccine. And if that third dose that we will be offered a month from now or two can go to one of my children, I’ll be happily giving that, because that’s where I think we should build our barrier.

Dryden: Now, as you worry about your children, as they go back to school, my understanding is that this summer, as you’ve been publishing all these big papers and talking to all of these reporters from around the world, your children presented a slightly different problem to you in terms of, like, finding a quiet space in your house where you could talk to The New York Times.

Ellebedy: Yes, that has been an interesting challenge as well. Yeah, they were at home — and this is something, obviously, new to me. It wasn’t really something part of our normal activity before the pandemic. Lots of Zoom calls, lots of have to stay at home with the kids, lots of social distancing and all of that. So yes, it has been an interesting time. They keep asking me, “When is the COVID going to end? When can we go back?” And they stayed at home for most of the last year. So it wasn’t an experience that we would like to repeat. We are hoping that we don’t need to go through this again. I’m sure many, many parents, especially of kids in elementary school, will be sharing the same experience. This was not fun time. I have to say, they asked me last year, “When do you think — when COVID will end?” And I was wrong. I told them, “It’s going to be May.” Given that this was when they asked me — last Christmas — when it’s going to end, I told them (that) given how the vaccine is doing, knowing vaccine, and we’ve seen the vaccine just being rolled out, I thought we would be in very good shape in May. And relatively, we were in good shape. But unfortunately, delta happened. So right now, when they ask me, I tell them I don’t know.

Dryden: With the current delta variant and with what you have found about the fact that vaccines are very effective against this variant, we have, on the other hand, seen a lot of what they call breakthrough infections. Is that because there’s so much more virus that people are being exposed to from delta, that the load that we get is that much larger? Or what is the reason for these breakthroughs? Or is it just because the more people who get vaccinated, the more people are going to have breakthrough infections, just because the vaccine isn’t 100% foolproof?

Ellebedy: Yes, that’s very close. I think one thing we have to also even take a step back and think about: Breakthrough infections are not really a failure. The goal of the vaccine is not really to prevent infection. The goal of the vaccine is to prevent severe disease and prevent death. And from that perspective, vaccines are working very efficiently. Even after six months. Now, coming back to delta, which made that point very clear, that even people who had been vaccinated can be infected and can transmit the virus. This is where I think the danger is from a variant like delta — because once the virus can replicate efficiently, especially in the upper respiratory tract, in our nose and areas where our first barrier to meet that virus. And we know that the vaccines are actually not really providing a huge immunity in that barrier. We have good antibodies that are circulating in our blood, but we don’t know how much of that is actually being shared with these very barrier sites like the upper respiratory tract in general. So it could be that a variant like Delta is taking advantage of that. But again, the vaccine itself, once the virus starts going deeper in our lungs, now we are seeing the difference. We are seeing people don’t need to go to the hospital. They are not as sick. One way to hopefully prevent that in the future is to try to develop a vaccine targeting the mucosal sites. And that’s intranasal vaccines, for example. And we have known that, that these will be more superior for respiratory pathogens. It’s just that we didn’t have the time.

Dryden: Some vaccines, MMR, they last a long time. Other vaccines, flu shot, we got to get every year. Where, in that spectrum, does the COVID vaccine fit?

Ellebedy: I guess this is the million dollar question — we’ve been asked that many, many times. And it’s a very important question. Unfortunately, I wish I knew the answer for it. Obviously, the clear difference between those successful vaccines you mentioned and the problem with influenza, which I’m very familiar with, is that the virus itself is either stable antigenically or doesn’t change its features, or is a virus that change features frequently like influenza. And these are the two extremes. I mean, when we started this, every one of us was hoping that SARS would be belonging more to the first category, or that the viruses that are more stable antigenically and we don’t need a booster in any sense. Over the last eight months now, we learned that this is not going to be the case with this virus. And not surprisingly, these variants came from populations that were not vaccinated. And then, we are seeing that the virus continues to evolve. So the answer to this question will really depend on how the situation with the variants evolve. If we get to a situation where we have enough people immune, either by vaccination, hopefully, or infection, then the virus will not be spreading as easily. It will not be circulating as easily. And then that will limit the ability of the virus to change its features. And consequently, it will be able — we will be able to control it with the current level of immunity and hopefully will not need any boosters in the future. Obviously, things can change. We don’t know what’s going to come next. I’m hoping that delta will be the most serious variant we have to manage. But I really don’t know at this stage.

Dryden: When you talk about flu shots and boosters, one of the things that you were working on before SARS-CoV-2 was trying to develop flu vaccines that could be given once and we’d be done. How does that work relate to what you’re understanding about about SARS-CoV-2 now?

Ellebedy: Our work with influenza actually has benefited us a lot in the last 18 months because it allows to have the infrastructure and the set-up here at WashU to actually be able to quickly adapt our teams and our capability to study the immune response to SARS-CoV-2 either infection or vaccination. The situation with influenza has been very challenging. We all were hoping, and we’re still hoping, that SARS-CoV-2 will not be an influenza, it will be less able to actually change and less able to evade our immune system or immunity, and that we will not need a regular shot for it. We never had a good vaccine against influenza, similar to what we are seeing now with SARS-CoV-2. So my prediction is that one of the things that actually we will benefit from, if there is any benefit from this pandemic, if there is any positive things we can take, is the RNA platform for a vaccination. I think this is a — this is one of the things, I think, 10 years from now, we will look back and think a major change in our way of developing vaccines and utilizing vaccines and vaccine platforms, is how the pandemic provided this opportunity for this novel platform to actually be utilized that broadly. So I have no doubt that there will be influenza vaccines that are utilizing the RNA platform. I think they will be changing a lot of what we are seeing with influenza. I think we will — I’m optimistic that these vaccines will actually probably help us control influenza in a much better way. Maybe it will be a shot every three, four, or five years.

Dryden: Before you published the paper about vaccines, you published a paper showing that even people who had had mild infections or asymptomatic infections were still making antibodies months later. A friend of ours saw the press release or read the paper, had had a mild case of COVID, and elected not to get vaccinated. Tell me how we convince that person that they need a shot.

Ellebedy: This has been an unintended consequence of our paper, many people thinking that if we are getting infected, we are protected for life. And we really have to make a distinction between having detectable immune response versus protected. Totally different things. What we said and what was very clear from the data that, yes, you will have — your body has developed — if you have a mild infection, your immune system has developed a memory that likely will continue for the rest of your life. That doesn’t mean, in any way, that you are protected for the rest of your life. Totally different things. Because you could have — first, as I started from the very first sentence, is that not all infected people respond similarly. So it doesn’t mean you’re infected. There are many reasons that you are infected or vaccinated and your immune response wasn’t optimal in any way. So you might not have developed, really, a great memory. So that’s number one. Number two is, even if you did, and yes, you have detectable, immune antibodies months and even a year later or two years later, that would have been OK if the virus didn’t change. But if we are telling you, and if we are seeing that the original virus is no longer circulating — 98% of the viruses circulating globally now are actually delta variant. So that original virus completely now doesn’t exist. What you have your memory recognizing is something that doesn’t exist anymore. And what you really need to be concerned or thinking about, “Is my immune memory that was generated by the infection a year ago still sufficiently able to recognize those shared features between the original virus and the delta variant?” If the virus didn’t change, you would have an argument. For anyone infected, you would have an argument. If the virus didn’t change. But now, once the virus changes, and not only changed, it acquired the ability to replicate more efficiently, as we are seeing with this delta variant. So that, now, completely changed the game.

Dryden: Is something similar happening with vaccines, because the virus has changed into the delta variant? Or is our immune response wearing off over time from the vaccine?

Ellebedy: One of the things that I was hoping to see is that at certain point, we will be offered a booster immunization based on one of those variants. And this is likely the reason — not likely, this is probably the reason why the CDC decided or the decision that we all heard, that proposal that next month, they will be offering a booster immunization. And this really was a surprise for many, many scientists. The reason is that we don’t see any need for it at the moment. But I understand this was almost a precautionary step, because you want to see people who are elderly who probably didn’t have a very robust immune response. And although we are not seeing any significant problem with this vaccinated population at the moment, but you can anticipate maybe a year or eight months after being immunized, the immunity starts to wane, which is a natural process. You don’t have to sustain high level of immunity because we have this immune memory. So I understand that part. What I don’t understand is, all right, I still don’t fully agree with: Do we really need that for the general population? Do we need the third immunization? Especially that’s not based on any of the variants, so it’s really not providing — it’s not training our immune system to recognize any of the novel or new features of the variants you are seeing. I’m hoping that this — again, this was a proposal and we are all waiting to see the events that will happen next month. But for the elderly, I think this will be important, to get a booster immunization.

Dryden: To elaborate on that a little bit, it would make more sense to you if the vaccine had been tweaked slightly to address a different feature that delta has rather than the original virus?

Ellebedy: Yes, exactly, actually. And one of the things that we are learning about the RNA technology is that you can actually include multiple different RNAs that — for example, you can include the original spike protein, which was the original vaccine, but also add to that one or two of the variants. And that would allow us to really broaden our arsenal of our immune cells that can target these different features or new features that these new variants are bringing. Right now, what we know that will happen is that, really, this booster immunization will engage these memory cells that we formed over the last few months after receiving the vaccination. And that, overall, probably will enhance our baseline of immunity.

Dryden: What about the thought that we, in the United States, will be getting a third shot while so much of the globe that is also suffering with delta still hasn’t had an opportunity to get the first shot?

Ellebedy: That’s another very important point that has been raised by many epidemiologists and public health experts, that, really, is that the best use of our resources, knowing that, again, this is a global problem, it’s not a U.S. problem? The most dangerous variants, the most variants of concern came from — right now, we know delta variant first emerged in India, where vaccination rate is very low. Before that, there was the beta variant, was first detected in South Africa. Again, where we know that the whole continent of Africa, the vaccination rate is very low. So it’s obvious that the virus flourishes in communities or places where there’s very low vaccination rate. So from a point of controlling a pandemic, should we actually spread this and make sure that the virus doesn’t have ground for continuing to evolve? It’s like building a higher wall or actually making the wall really, covering more ground. And I think, at this stage, given the success of the vaccines, our wall seems to be high enough. So I think our priority should have been, really, to expand that wall and really try to make that barrier cover more ground so when we cut the holes and the virus doesn’t get to us.

Dryden: Ellebedy says, for now, it’s important for people with access to vaccines to get them and for access to vaccines to be expanded, and for those things to happen as soon as possible so that the virus doesn’t get the chance to evolve into new variants, because even though the vaccines provide pretty good protection against delta, that might not continue to be the case as SARS-CoV-2 continues to evolve.

“Show Me the Science” is a production of the Office of Medical Public Affairs at Washington University School of Medicine in St Louis. The goal of this project is to keep you informed and maybe teach you some things that will give you hope. If you’ve enjoyed what you’ve heard, please remember to subscribe and tell your friends. Thank you for tuning in. I’m Jim Dryden. Stay safe.

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