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Can the Same Vaccines Protect Against New COVID Strains?

— Questions about long-term efficacy become more insistent

MedpageToday

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As many as a dozen COVID-19 variants are knowingly circulating worldwide. Among them, B.1.1.7 and B.1.351, the highly transmissible strains that originated in the U.K. and South Africa, respectively.

As more vaccines continue to push forward for emergency approval worldwide, we're still learning the effectiveness of the current vaccines against the new strains; and how the new mutations mean even those who have already had COVID-19 may not be immune from reinfection.

To explore the new strains and what it means for vaccination efforts, future mutations, and herd immunity, Angela Rasmussen, PhD, a virologist with Georgetown University's Center for Global Health Science and Security, joins us on this week's episode.

The following is a transcript of her interviews with "Track the Vax" host Serena Marshall:

Marshall: I want to jump right in because we have all of these new strains that we're hearing about in Brazil, South Africa, U.K., the CDC has called them a threat to the U.S.

How concerned should we really be about this?

Rasmussen: So I think we need to be very concerned, but we also shouldn't freak out. I think that these variants, what they've done in other countries, where they've rapidly become dominant. And in some cases, such as the B.1.351 variant from South Africa, may not be as neutralized as well by antibodies elicited by the vaccines.

We need to make sure that these variants are not able to spread further within our population. And one way to do that is through vaccination, of course; but right now we don't have enough vaccine supplies to vaccinate enough people quickly enough. So that means that we also should be directing our energy and our concern to reducing transmission as much as possible through other means.

And that means I'm doubling down on the precautions that we have been taking for the past year. So masking, physical distancing, avoiding enclosed spaces, not having gatherings unless they're absolutely necessary. Improving ventilation, if possible. Washing our hands and disinfecting high touch surfaces; by taking all of those measures and applying them as much as we can in any given situation, we'll be able to reduce our transmission risk until we can ramp up vaccination to the point that enough people are immunized.

Marshall: And our goal here at 'Track the Vax' is to really dive into the vaccines. But before we get into how the vaccines might or might not work against these strains, I want to break down how these strains came to be. Explain for us: is COVID mutating at a faster rate than perhaps other viruses, like the flu? Is that even an equivalent comparison?

Rasmussen: So that's not a very good comparison at all because SARS Coronavirus-2 is mutating but actually not at a faster rate compared to many other RNA viruses. Coronaviruses... well, let me back up and explain mutation. So mutation is just: what is described as essentially a spelling error. When the enzyme that copies the genomes for these viruses is copying them...it can sometimes essentially make a typo. That typo is called a mutation. Sometimes mutations have absolutely no impact at all. Sometimes they're bad for the virus. Sometimes they give the virus an advantage. Those are the mutations that we are concerned about -- the advantage ones. The ones that make the virus better at doing what viruses do, which is replicating. Any mutation that does that is going to be of concern to us.

Now again, most mutations actually don't give any kind of advantage and they can actually be detrimental to the virus, but if the virus gets enough opportunity to replicate we will eventually, through random chance, just acquire some of those mutations. Now, coronaviruses don't mutate as rapidly as the flu for a couple of reasons.

One is that they actually have an enzyme, in addition to the one that replicates the genome, that acts as sort of a spellchecker. And it can correct some of the mutations that are made. So it has a lower mutation rate in general than other RNA viruses, such as influenza. It also doesn't have a segmented genome, meaning its genome is all just one big piece of RNA.

So influenza has a segmented genome and that means that if a person or an animal is infected with two different influenza viruses, those genome segments can sort of, it's called reassortment. They can sort of be shuffled together in unpredictable ways, like a deck of cards. And this allows new variants to emerge very rapidly.

That's not the case with coronaviruses either. So it is mutating more slowly than many other RNA viruses and it can't re-sort; but at the same time, because there has been so much transmission and the virus has gotten so many different opportunities to replicate.

Marshall: We've heard that some of these mutations, the way where they're coming in from places that haven't perhaps had the strongest lockdown measures. So you started out saying: if we started washing our hands, doing more lockdowns, mask wearing, et cetera, we could maybe put some of these strains to bed. Is that because the strains are occurring in places where the virus has more opportunity to infect a wider swath of the population?

Rasmussen: That's right. So anytime the virus is getting a lot of different opportunities to replicate, such as in places where there is widespread transmission and a lot of new hosts for the virus, that's going to increase the likelihood that these variants will emerge. And that also unfortunately increases the likelihood that new variants will emerge in the future, which is why it's even more important to get transmission under control.

Marshall: Are we expecting to have a U.S. virus strain? I mean, the U.S. has the highest death toll in the world right now.

Rasmussen: Well, we already certainly know that there are variants that have emerged in the U.S., whether or not they are of concern, meaning that they have some of these mutations that will confer some type of advantage to the virus remains to be seen. But we also are having a harder time tracking the new variants that might emerge here just because we're not doing as much genomic surveillance as other countries.

So it's entirely possible that there could be "U.S. variants" that are circulating that we should be worried about, but we just don't know about yet. Again, that's another reason to really crack down on trying to reduce transmission as much as possible, so that any variants that might have emerged here aren't going to rapidly take over.

Marshall: That's kind of a terrifying thing to think about that we could have these U.S. strains that are going to emerge and we just won't know about it.

Rasmussen: I mean, it's certainly scary. What to me is scarier, though, rather than a hypothetical future U.S. variant, are the P.1, B1.351., B.1.1.7 variants, which we know are already in the U.S. Not being able to track those as well as we'd like is a concern that I have all the time. I think that that's why, again, I can't emphasize enough how important it is to take as many measures as possible to reduce transmission, because we already know that these variants are here.

Marshall: Will we see re-infection with these new strains go up? Will the numbers start to rise again because people can be reinfected with the new strain?

Rasmussen: So the jury's really still out on how common re-infection is. I realize that there's that one alarming study from South Africa that suggests that vaccination or prior infection might have a minimal impact on being susceptible to the variant that is circulating there, the B.1.351 variant, but that's one study.

We actually don't know if all these variants are going to be able to completely evade immunity from prior infection. So rather than worrying about that, I really encourage people, if you don't want to get reinfected, don't get infected in the first place. So again, take all those measures possible to reduce your exposure risk.

Marshall: Good message for sure. And let's talk now about those vaccines. Will the vaccinations that we've seen ramp up throughout the country, in addition to the mask wearing and prevention measures, will that mean that we can reduce these strains and their spread? Will we be able to vaccinate our way out of these new variants?

Rasmussen: So I don't think we'll be able to completely vaccinate our way out of them. Just the supply issues. Doing the math, and that's completely ignoring all of the distribution issues we have. Doing the math on the number of doses that we have. It's going to be very unlikely that we would be able to vaccinate enough people in the population to reduce the risk of these variants posed by vaccination alone.

I think that if we really, again, apply these different risk reduction measures, in addition to ramping up vaccination, that will give us a much better shot at preventing these variants from being commonplace and widespread in the U.S.

Marshall: Is it important to get vaccinated with the doses we have, even though we don't really know...the sides are starting to come out. So we're starting to see that some of these vaccines do protect against some of these variants, but we don't really know the full picture of protection with these new strains.

So are those vaccines still going to be helpful against these strains?

Rasmussen: Absolutely. All the data that we have so far suggests that even in situations where the vaccines might not protect completely against symptomatic COVID; they all seem to remain effective against severe COVID-19. And that's really the most basic and most important thing that we want these vaccines to be able to do.

We want to be able to keep people out of the hospital. If somebody is going to get COVID, we want to make sure that they don't die from it. So I think that right now, we still don't have any news that any of these vaccines or any data indicating that these vaccines can't protect against that severe COVID-19 that actually kills people. That puts people in the hospital and strains our healthcare system.

So I think that we should absolutely take the vaccines as soon as we have access to them. And that is what I'm planning to do. That's what I've encouraged all of my family and friends to do, as well.

Marshall: But in South Africa they have suspended the AstraZeneca vaccine. That's one that hasn't been even put forward yet in the U.S. for FDA approval. But the preliminary data there showed that it was ineffective against the primary variants circulating in the country. And in some ways, undermined public confidence in the vaccine.

Rasmussen: That's correct, but that study only looked at mild or moderate COVID-19. It did not look at severe COVID-19 and the data from the Johnson & Johnson and Novavax trials suggest that those vaccines do remain protective against severe COVID-19 in the case of people infected with that variant. I think that the decision to suspend the use of the AstraZeneca vaccine, of course, is the decision of health officials in South Africa. But I don't necessarily think that that's warranted based on a single study, essentially.

I think that there is still quite a bit of value if that vaccine is capable of protecting against severe outcomes. Now that said, I haven't seen data that suggests that it's not.

Maybe that data exists? But from what I can tell these vaccines remain effective at preventing severe COVID-19. For that reason, I don't think that any of the vaccines should be suspended. But, of course this is an emerging area of research and data may be uncovered that would change my opinion on that.

Marshall: One of the things we do know with some of the research that is starting to be released when it comes to these new variances, the mRNA vaccines appear to offer a little bit more protection than the AstraZeneca or Johnson & Johnson ones, which use that adenovirus vector format. Why would perhaps the mRNA ones offer a little bit greater protection than the more traditional vaccine route?

Rasmussen: Well, that's a great question. And to be honest, I don't completely know the answer to that. Certainly, one of the things to keep in mind about that is that the trials also have different end points and different vaccine regimens. So the AstraZeneca vaccine is two doses of a chimpanzee adenovirus vectored vaccine given up to 12 weeks apart. The Johnson & Johnson vaccine is a human adenovirus-26 vectored vaccine. That's only given once.

Whereas the mRNA vaccines have no virus in them. They're just mRNA given in two doses, three to four weeks apart. So they're completely different vaccine regimens. They're completely different vaccine technologies. It could have everything to do with the types of adenovirus, vectors that are used.

It might have something to do with the fact that Johnson & Johnson is a single shot. In the case of AstraZeneca, it may have something to do with the fact that there could be vector immunity. So that's immunity against the vaccine itself rather than against the spike protein from SARS coronavirus-2 that the vaccine is expressing. It could be a lot of different things, but it's really hard to compare across different dosing regimens, different vaccine technologies, that sort of thing.

So my short answer is, I don't know. And my longer answer is that it could be a variety of different factors.

Marshall: Yeah, there's a lot we are learning on this it seems every day on this, for sure. When it comes to those different types of vectors, how easy would it be to adjust them or switch them? Switching mRNA vaccine so it is specifically targeted to one of these new strains?

Rasmussen: So the nice thing about all of these technologies is it's actually relatively easy to change all of them. So the mRNA vaccines, you're just synthesizing essentially a piece of mRNA. That's very, very easy to change from a technical point of view.

Same with the viral vector vaccines, although it's a little bit more complicated. They still are recombinant vaccine viruses and they can be edited quite easily in a lab to cover these variants.

I think that what we might be looking at in the future. One possible scenario, we start looking at heterologous boosting. Which is boosting with a different vaccine platform than what you were initially vaccinated with. The same thing is true by the way, for the protein subunit vaccines, such as Novavax as well.

It's relatively easy to change them. Some of the more complicated features of this would be in the manufacturing part. It is a little harder to manufacture viral vector vaccines than it is mRNA or protein subunit vaccines. So it may be that people who got vaccinated initially with Pfizer or, or Moderna, might be getting a Novavax booster.

Or people who got vaccinated initially with Johnson & Johnson or AstraZeneca might be getting a Pfizer or Moderna booster that addresses the variant. And this is something that we really need to look into to have the maximum flexibility in terms of boosting to account for variants that might emerge.

Marshall: Is there any research being done on cross boosting, cross vaccination across the different types of vaccines?

Rasmussen: I'm not aware of any clinical trials yet. But I know that people are definitely talking about heterologous boosting. I imagine that also once these boosters start being rolled out, probably that will be looked at. I think that going forward, it's going to be really important that we do that.

But historically, you know, with many other vaccines, they have looked at heterologous boosting and heterologous dosing regimens. This is not a new concept in terms of vaccinology. So there's no reason to think that it would be bad or less effective if you were to sort of start mixing and matching vaccines. Right now, that's not going to happen just because of the supply issues with most of the vaccines. But going forward, I think, especially if we have to start developing boosters for emerging variants, we probably will get a lot of experience with using heterologous vaccine regimens.

Marshall: So, what about these mRNA vaccines that require two doses? Could you then do a Pfizer for number one? And a Moderna for number two?

Rasmussen: Probably. Honestly, I mean, those vaccines are very, very similar. I wouldn't be surprised at all to see that there was really no difference using heterologous dosing. With dosing with Pfizer and Moderna. That hasn't been done. I imagine that experiment might happen naturally in some cases when somebody accidentally gets a second dose from the other company than what they got their first dose. But to my knowledge that hasn't been studied rigorously, yet.

Marshall: What about if we have to switch these vaccines and then go through this whole FDA-EUA approval again. That takes time. Would they need new studies to examine the specific strains and changes to these vaccines?

Rasmussen: So they would. But the question for me is what are those studies going to look like? I don't think they're going to require a full phase three clinical trial similar to what was needed to authorize the vaccines in the first place.

And we routinely do this with vaccines. We do this with the influenza vaccine every year, for example. And it doesn't require extensive phase three clinical trials to do it. So there is a regulatory framework for this in place. My question is really what that looks like for SARS-coronavirus-two vaccines. But I do know that the FDA and its regulatory equivalents in Europe and in other countries are already talking about this.

They're talking about what that process is going to look like and how long it's going to take. Because I think everybody understands that time is of the essence with regard to boosting against these variants.

Marshall: We've heard a lot of talk about not even going forward with the second dose for some of these mRNA vaccines. J&J is only one dose, but the mRNA, AstraZeneca -- those are all two doses as you explained. If we only give one of those doses because of the supply chain issues, will we see new strains pop up in the way we saw antibiotic-resistant bacteria mutate and become resistant to those drugs?

Rasmussen: Well, it's not completely analogous to antibiotic-resistant bacteria. But we certainly could see variants emerge as a result of these incomplete vaccination regimens that people have proposed. So, so far, all of the data suggests that in order to elicit a robust neutralizing antibody response, you really do need the second dose for those mRNA vaccines.

There's one exception. And now three studies have shown that people who previously had COVID-19 who already have antibodies to COVID-19 end up eliciting very robust neutralizing antibody responses with just one dose of the vaccine. And that's essentially because that one dose of the vaccine is acting, effectively, as a booster shot for their prior natural immunity.

But in people who've never had COVID-19, it does suggest that for a maximum neutralizing antibody response, you really do need the second dose. And where that's important for variants is that if you do not have high levels of neutralizing antibodies that are sustained, you might have sort of, subpar levels of antibodies circulating.

And that essentially gives the virus an opportunity to replicate in the presence of some antibodies that would target it. And that will select for variants that will not be targeted by those antibodies. So the sub-protective immune response that one dose might elicit could actually be worse in the long run in terms of giving sort of a good training environment for new variants to emerge in.

So for that reason, I think that all of the data is really suggesting that we do need to follow through with the second dose within the timeframe that has been tested. Just to make sure that what we know works is going to work. Then potentially study different timing, different dosing regimens going forward.

For now, I'm pretty staunchly opposed to single dose vaccine regimens, just because the data doesn't really support that they will be protective, particularly in the long term.

Marshall: Okay. So looking here stateside. What projections can you make looking forward about distribution, vaccination rates, hospitalization rates, and the variants continuing to circulate?

Rasmussen: Boy, this is such a hard question to answer, for a variety of reasons.

And let me tell you why my answer to this is still: 'I don't know.' One reason is that it's very difficult to say where we're going to be at with vaccinations. Johnson & Johnson has also said that due to manufacturing issues, they're only going to have about 4 million doses available until April.

So that's not really gonna make a huge dent when we need to be vaccinating hundreds of millions of people. Four million doses is still kind of a drop in the bucket. So some of this will depend a lot on how quickly and efficiently we can roll out these vaccines. We're still not doing a good enough job of getting vaccines to some of the people in the communities that are most at risk.

Another issue is that the restrictions have been lifted in many states, but they're very different from state to state. And from state to state, and even within those states from community to community. There are different levels of prevalence and there are different types of behavior that people are engaging in that can change their risk for contracting COVID-19.

While these variants are still low prevalence here, we can't rely just on vaccination because, again, we don't even know how quickly we're going to be able to immunize large portions of the country -- much less in individual communities. So I think it's a very, very, bad idea to be opening things back up, even if we're doing so, "cautiously."

What I would rather see is people hanging on just a little bit longer. Until we can get more vaccines rolled out, continue to reduce transmission. Then we will be able to actually open up sooner, for good. Sustainably in the long run. What I have been very frustrated by are these constant flip-flopping back and forth between: 'okay.... transmission's down, let's open things back up. Oh, no transmissions back up again. Let's shut back down again.'

People are getting very tired of this. And I think that it would be more helpful if people knew that if they took extra measures now to reduce transmission, got vaccinated. Then in a couple months, we could start relaxing those restrictions and opening back up for good and not be trapped in this continued cycle of restrictions, fewer restrictions, more restrictions, and so on and so forth.

Marshall: That's what you see happening if these viruses, these variants continue to spread.

Rasmussen: I think if these variants continue to spread and particularly if the variants do cause some reinfection....if natural immunities are not completely protective against them at population scale, that puts us back in this never-ending cycle of restrictions, fewer restrictions, more restrictions again. I think that by controlling the variants now, before they become prevalent in the U.S., and by simultaneously ramping up vaccination that would keep us from getting stuck in this cycle again with these variants.

Marshall: Dr. Rasmussen, Thank you so much for joining us with these fascinating insights into the strains and likely the strains they'll put on the vaccination efforts.

Rasmussen: Oh, really my pleasure to be here. And my take-home message is keep yourself safe for now and get vaccinated when you can.