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As the U.S. hits the half-million death mark from COVID-19 — a grim milestone that is equal to roughly the entire population of Atlanta and more than that of Miami — a new weapon is being added to the COVID-19 vaccine arsenal.
Johnson & Johnson is seeking emergency use authorization for what would become the U.S.’s first one-dose and non-mRNA COVID vaccine. It employs adenovirus vectors, a technology that has been used in labs for decades and was approved for the Ebola vaccine by the FDA in December 2019. It’s the same technology that AstraZeneca/Oxford and Sputnik V use.
Still, questions remain on how these vaccines may be different than mRNA or similar enough to other existing shots to encourage vaccine uptake. To explain how adenovirus vectors work and what to expect from the new products, Daniel Griffin, MD, PhD, chief of infectious disease at ProHEALTH Care, an Optum unit, joins us on this week’s episode.
The following is a transcript of his interview with “Track the Vax” host Serena Marshall:
Marshall: Dr. Griffin, welcome to Track the Vax. I want to talk today about adenovirus vectors and the new vaccines that are coming out. But before we do that, let’s talk about adenoviruses. Those are something that cause a range of illnesses that people get every day. Right?
Griffin: That’s correct. I think people are unfortunately familiar with adenoviruses. These are the common cold viruses and, you know, I think all of us, at some point, at far too many points, you know, you’ve had the sniffle. You’ve had the cough. You felt crummy. If it’s a cold it’s often adenovirus.
Marshall: So why would you use an adenovirus for a vaccine? Why does that make a good mechanism to deliver the vaccine, specifically when it comes to COVID vaccines?
Griffin: There’s a couple reasons. And I think the first is the common cold issue, and this is a mild virus. It’s not something that we worry about. It’s an inconvenience and someday someone will cure the common cold and that’ll be exciting. We won’t have that. But this is a mild respiratory virus.
It also is one that we have a lot of experience making even more mild. So we can actually use this common cold virus as a delivery system to allow our immune system to see spike protein. To see basically something that our immune system can learn to respond to; can hopefully allow us to develop an immune response so we don’t get sick with COVID.
Marshall: So these have been termed: the tried and true vaccine mechanism, when it comes to COVID. Specifically compared to the mRNA vaccines, what vaccines currently use this or employ this technology?
Griffin: I think that is interesting. We definitely have a lot of people and they say, “yeah, all these mRNAs, when’s the normal coming? I want the normal vaccine.” I think there’s a couple of things when people say they want the normal vaccine.
One is they, I think they’re thinking of something like the J&J. I just want to get one shot and then be done.
Marshall: One and done. Exactly.
Griffin: One and done exactly. I’m sure that will be part of their marketing campaign. They also want a vaccine that: I want a vaccine that like hundreds of thousands of people have gotten this technology. I don’t want to be one of the first people.
And that’s where the adenoviral vaccines come in. We’ve been working with these really since the 1970s. We’ve been studying, working with these. So not just two decades, but I guess we’re going to say 50 years, five decades.
This was the technology that was used when they had issues with Ebola, right, in West Africa. They were very able to quickly get a couple of these up and running. Two Ebola vaccines were actually engineered using the viral vector technology, and were used in a couple hundred thousand people in the outbreaks in West Africa and the Democratic Republic of Congo.
So yeah, in many ways this is technology that hundreds of thousands of people have used. We have a side effect profile. We have safety profile data. And now with AstraZeneca and J&J we have a couple of COVID vaccines with really good, good data as well as really impressive safety profiles.
Marshall: Now, this is interesting, Dr. Griffin, because you mentioned that the research goes back five decades, but you only really mentioned the Ebola vaccine. Is that the only vaccine that currently exists because that’s only a couple of years old?
Griffin: Yeah. The challenge with vaccine technology has often been the market for our newer ideas. Right. You know, we do the flu vaccine, a number of the childhood vaccines. But we really have a price point for vaccines being: “Oh, it’s only going to cost a few dollars.”
I don’t think we’ve appreciated until this current pandemic, how valuable it can be to spending money on vaccines and getting new technologies out there. We’ve been working with these viral vectors for decades now. But it wasn’t until we had issues like Zika, RSV, malaria. And then as I mentioned, the Ebola outbreaks, where we really took these viral vectors and really got them out there to hundreds of thousands of people.
Marshall: But these viral vector vaccines have also kind of gotten a little bit of a bad rap specifically when it came to some research done with HIV. I know there’s concern that there’s an issue with preexisting immunity and adenoviral vectors. Can you explain why people should not be worried about that little bad rap that came through with HIV?
Griffin: HIV is tricky. And unfortunately too tricky. I grew up in Greenwich Village in the early eighties when, you know, when HIV was really sweeping through our country and still continues to be a problem today. Two of the issues with HIV, one is it’s constantly changing. So it’s such a hard target because as soon as you think you know what you’re going after, it’s already changed its genetic code. We’re starting to see a slower issue with COVID on those lines. But the other is when you activate cells, the cells that you activate are actually the ones that are most vulnerable to HIV.
So when you try to use a vaccine and try to turn on the immune system, HIV takes advantage of that. So we’re lucky in certain ways with COVID in that when you turn on the immune system early, when you give someone a vaccine, we’re seeing really great results. Some of the attempts to use this technology in HIV, unfortunately, as you bring up, they did not go well.
Marshall: And that’s not something though that we’d have to worry about when it comes to these COVID viral vector vaccines.
Griffin: No, we really don’t. I mean, people know with COVID that there’s this early viral phase and then followed by an inflammatory phase. But what we’ve seen is that if you can give someone protection with a vaccine so that they don’t have much of that early viral phase, then we’re not seeing that they go on to develop any sort of an inflammatory issue.
So no. These concerns are not there for COVID. And the other side of the coin and just make sure I throw this in, is that with COVID, it just doesn’t change as quickly. It is changing. But these vaccines can actually change as quick as the virus changes.
Marshall: So let’s talk about some of these vaccines that are using adenoviral vectors. We know that you mentioned Johnson & Johnson, AstraZeneca, also Sputnik and Russia. How are they each different from each other? Is it kind of like the mRNA, Pfizer and Moderna ones where they’re relatively similar, just different research mechanisms in place?
Griffin: I really say the difference between Moderna and Pfizer is whether you’re getting your Coca-Cola in a can or a bottle, right? The Moderna, maybe you can screw the cap back on.
Marshall: That’s a good analogy.
Griffin: I don’t think there’s a huge, you know, same as Coca-Cola’s inside, you know? And I think the Moderna and Pfizer, it’s the same RNA, it’s the same stuff inside the packaging. Packaging’s a little different.
But here with Sputnik, with the AstraZeneca and the J&J, they’re using slightly different adenoviruses. So, there are a number of adenoviruses. You can take an adenovirus from a chimpanzee, and that’s what they’re using at AstraZeneca. They took a chimp adenovirus, the original ChAdOx.
What the Russians are doing and I think this is clever, is they’re using two different adenoviruses. One for the delivery of the initial and then a different one for the boost. And then J&J is actually just using one adenovirus, because you know, they’re hoping for a one-shot, one and done vaccine. Why would you use these different ones?
Part of it is the idea that we do have a concern, and fortunately I don’t think this is panning out, that, “Ooh boy, if you had that particular adenoviral infection before, maybe that would somehow prevent you from having a good, robust immune system.” We’re not seeing that.
With the Russians, that was their idea. You don’t want to have a really strong reaction. Now you’re immune to that adenovirus. Hey, what about focusing on getting immune to COVID? So that that’s their idea behind it. But again, maybe this goes to which car you’re putting that spike protein antigen in. So maybe a little bit different in the packaging and the delivery system. But ultimately these are ways for your immune system to see the spike protein, so it can learn how to respond and protect you against COVID.
Marshall: No, we’ve seen the efficacy for these adenovirus vector vaccines to be a little bit different in some cases, a little bit lower than the mRNA ones. Why is that? Is that because of the packaging or something else?
Griffin: So we don’t know, to be honest, right? Vaccine technology is, you know, learning on the fly here, how to get the best response. Most people, to be completely honest, were shocked at the efficacy that we saw with the mRNA vaccines. I mean, they really work well. And, you know, is it that you’re delivering it as an RNA package so you’re also getting the immune system all excited about how to respond to, “Hey, there’s a foreign RNA like COVID virus has.”
We’re not sure exactly, but, I want to draw, what I think is a really critical distinction is when you look at the ability of any of these vaccines to prevent you from dying of COVID. Once you get out to about six or seven weeks after you’ve started your vaccine regimen in a two dose series or six to seven weeks after you’ve gotten your J&J or your vector based vaccine.
You’re not going to die of COVID. I mean, your chance of dying a COVID is really pretty much erased. And that’s huge. A little bit of differences; you know, whether or not you get the sniffles or a mild case. But what I think a lot of us really care about, “Am I going to end up in the ICU? Am I going to end up on a ventilator or am I going to die of COVID?” All the vaccines are tremendous at preventing that from happening.
Marshall: And that’s definitely good news when it comes to all of these. J&J’s likely the next one to gain emergency use authorization here in the U.S. When they start to roll those vaccines out, what kind of side effects could we expect? Will they have similar side effects to what we’ve heard with the mRNA ones?
Sore arm, maybe a little weakness. You know, they say when you get those symptoms, it’s a good, robust immune response. Will that likely be similar for vaccines with adenovirus vectors?
Griffin: I have to say, if you’re looking for a sore arm and an excuse to miss a day of work, you may be disappointed with these vector-based vaccines. They tend to be incredibly well tolerated. At most it’s like getting a flu shot. So, you know, don’t expect to get those fevers, that really sore arm.
Don’t expect for your coworkers to miss a day at work. That’s actually one of the nice things about the adenoviral vector based vaccines. Very similar as far as, we talk about reactogenicity, very similar side effect, right up front profile to your flu shot.
Marshall: Now we’ve heard a lot, Dr. Griffin, about these new strains that are popping up. They said one of the benefits of the mRNA technology is it’s very easy to just tweak that vaccine to adjust for the new strains.
Is that the same with adenovirus vectors?
Griffin: Yeah. I will say when the COVID, when the virus that causes COVID, so when SARS-CoV-2 changes its genetics a little bit. When we end up with these variants. It really doesn’t take very much for the mRNA, basically you’re putting a slightly different bit of RNA in your package.
It actually is not that much harder to go ahead and do this with the viral vector vaccine. So, when they talk about easier, we’re talking about days versus a couple of weeks. I think that the viral vector vaccines are also something we can very easily update as the virus updates itself.
Marshall: That’s good news I’m sure for everybody who’s joining us.
I want to come back to something you said earlier, Dr. Griffin, about potential immunity to the different, adenoviral vectors. Now that is a problem for these boosters might not work as well, right? Because the bodies can develop immunity to adenoviral vectors. So how would they adjust for that? If you already, I mean, that’s what we’re seeing in South Africa, right? With the AstraZeneca and some of the older people not being recommended to get that specific brand of vaccine?
Griffin: You know, that is definitely something we’re gonna have to learn about as we go forward. And this is why I think it’s fantastic that we have so many options out there. You know, we talked today about that the mRNA vaccines, which are already out there and ramping up here in the U.S. and hopefully more around the world. AstraZeneca, which is in some places and J&J.
We’ll probably have protein-based and others, and sorry for leaving Sputnik V out again, but no, that might be an issue. There might be certain parts of the world where you say, “Ooh, we want to use the J&J; other parts of the world where we say, hey, let’s get the Russians to get Sputnik V here.”
So there may also be the issue that you want to alternate; like, you know, rotating your crops or something. So I think as we go forward, we’re going to learn more about boosters. About what’s the best vaccine in different populations. But that might be one of the issues with AstraZeneca.
The other issue, which I will bring up, so sort of getting into the weeds here, is that most of our vaccines take the spike protein and present it to our immune cells in sort of this fixed form. Before it undergoes a conformational change and they change a couple of amino acids, some proleins to make it look like a pre-fusion spike.
AstraZeneca didn’t do that. So it actually is this post-fusion change. And it’s not clear to me. I don’t think we know yet whether or not AstraZeneca was a little less effective because of that, or because it has to do with the delivery system they’re using, the chimp adenovirus.
Marshall: Now, when it comes to immunity, that’s something we’re still learning about, especially how long that immunity from these vaccines will last. mRNA because it’s never been in a phase three clinical trial, we really don’t know how long the immunity from that type of technology will work. Do we have any guidance on what we can expect when it comes to immunity from vaccines that are delivered through the adenovirus?
Griffin: I think again, we’re going to have to wait for the data here. You know, with the mRNA vaccines, we’re already starting to hear from Moderna, I think, encouraging reports. That it looks like those antibody titers, those neutralizing antibody titers stay high for periods of time. They’re saying maybe a year or two. So maybe a yearly boost there. We’re hoping we see the same things with the adenoviral vectors, but, interesting enough, I mean, this is sort of a positive spin the longer you wait initially, actually it looks like those neutralizing, antibody titers keep rising. Right?
Marshall: With the adenoviral vectors?
Griffin: Yeah. When you look at two weeks, four weeks. That was why we said: Hey, after seven weeks, that’s when no one’s going to die once they got their J&J vaccine. It was because those antibody titers keep rising and that’s something we’ve seen with other vaccines through the years.
So, it may be that at three months, six months, you may actually have more immunity. And I’m going to say, you probably, have more immunity than you did four weeks after the shot.
Marshall: So, when we look at the other vaccines that have used this technology, like Ebola, do we know how long that immunity lasts when its delivered through an adenoviral vector?
Griffin: So, I don’t.
Marshall: Okay, I just wanted to know if there was any background there.
Griffin: As soon as we get off, I know what I will be looking up.
Marshall: Dr. Griffin, I think you answered all of our questions when it comes to this technology, when it really comes down to it, it sounds like if you have adenovirus vector or an mRNA, they really kind of work in the same way.
Griffin: It really is. The whole name of the game here is showing your body the spike protein from SARS-CoV-2 so that your immune system is ready to respond, should you encounter the virus that causes COVID-19. So yeah, it’s just different delivery ways. Either, you know, serving up the mRNAs and your body’s got to make the protein or giving a viral vector. And again, your body’s gonna make the protein down the road.
I think at some point we’ll probably have a vaccine where we just show you the protein and you get the immune response.
Marshall: Great. Well, thank you so much for joining us at Track the Vax.
Griffin: Oh, it’s been my pleasure.
Last Updated February 24, 2021