Watch the AMA's daily COVID-19 update, with insights from AMA leaders and experts about the pandemic.


In today’s COVID-19 Update, a discussion on vaccines and how to protect against variants with Paul Offit, MD, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia.

Learn more at the AMA COVID-19 resource center.

Speakers

  • Paul Offit, MD, director, Vaccine Education Center, Children's Hospital of Philadelphia

AMA COVID-19 Daily Video Update

AMA’s video collection features experts and physician leaders discussing the latest on the pandemic.


Unger: Hello, this is the American Medical Association's COVID-19 Update. Today, we're discussing vaccines with Dr. Paul Offit, the director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia. I'm Todd Unger, AMA's chief experience officer in Chicago. Dr. Offit, first, thank you so much for being with us today. We're going to jump right into this and ask about a topic that's on everybody's mind right now, which are the variants. What do we know about them, and are the vaccines that we have effective against them? How worried should we be?

Dr. Offit: So to put this in perspective, this is a bat coronavirus. It made its debut in Wuhan, China, in November 2019. As it started to march across the globe, it formed his first variant, probably from Europe. It had the fancy name of D614G variant, and that was the first variant, and then it moved from Europe into the United States. There have been a series of other variants that have formed. There's the U.K. variant, there's the South African variant, there's the Brazilian variant and most recently, the California variant. The critical questions for these variants are not that they would occur. Of course, they're going to occur. As this bat virus adapts itself to growth in people, it's going to create variants. The critical question is, are there going to be functional differences with these variants? In other words, are they more contagious? Which is generally true for many of them. Are they more virion, meaning more likely to cause disease? That really doesn't appear to be true.

And third, and far and away most importantly, will they escape recognition by vaccines? Because the vaccines really are all generated for that original strain that really came out of Europe, that so-called D614G variant. That's really how all the vaccines are made, to prevent that particular variant. So will it protect other variants? Now, it certainly looks like it's going to protect the U.K. variant, because they're so similar that immunization with one I think would protect against disease caused by the other. The one that's more worrisome is this so-called South African variant. And now we're seeing data generated from the Johnson & Johnson trial that was performed in South Africa that it does somewhat escape recognition, but not entirely. And really that's what you worry about.

What you worry about with these variants is, if you've been given a vaccine or you've been naturally infected, and then you're exposed to, let's say, the South African variant of this SARS-CoV-2 coronavirus, do you then get hospitalized or worse, go to the ICU, or worse die? And so far there is no evidence for that. So as long as these vaccines can prevent against moderate to severe disease, I think we're good. And so far, that's where it stands. Now, that said, I think we need to prepare for the fact that these variants may completely escape vaccine recognition, which if that's true, we're going to need to have second generation vaccines.

Unger: Well, that's it exactly. Let's just follow up on that. Are we going to, at this point, do you think have to reformulate vaccines to be more effective against these variants? And what does that process look like? Is it starting all over again? And how fast is that?

Dr. Offit: Well, should we get ready for the fact that these variants as they pop up may completely escape vaccine recognition? Yes. How does that work? Well, it's actually fairly easy to construct the variant. I mean, for the messenger RNA vaccines, which are made by Pfizer or Moderna, or these so-called replication defective, simian or human adenovirus vaccines, which are made by Johnson & Johnson and AstraZeneca and now the Russian group. Can you reconstruct them fairly easily? Yes. You just reinsert the different gene. That's easy. The hard part, the really hard part as we're learning, is mass production, mass distribution and mass administration. That's going to be just as hard as it's been now.

Unger: How long does it take to construct something new for a variant like that? Are we looking at another year?

Dr. Offit: To construct it, you can probably do it in a week. The problem is mass producing it.

Unger: Yeah.

Dr. Offit: And do you want to then add it? In other words, for the mRNA vaccines, you could argue that you would include in that little lipid nano particle, that fatty drop of not only the mRNA from what we're doing now, which is that first variant, the D614G variant, but also, let's say, for the South African variant or the Brazilian variant, you can put more than one mRNA in that capsule so you can get essentially a multivalent vaccine. So making that I think wouldn't be that hard, or constructing it wouldn't be hard. Mass producing it is always hard. I mean, as they say in the vaccine world, the hardest part of making vaccines is making vaccines. And I think that's always true.

Unger: I want ask you a big picture question about variants for those who might not understand it. Why did they emerge and how does this happen?

Dr. Offit: So for viruses like SARS-CoV-2, it's a so-called single-stranded RNA virus. So its ability to proofread itself when it reproduces itself is poorer than, say, for DNA vaccines. So there's always variants generated. The question is, are those variants functionally different? So, for example, flu is a single-stranded RNA virus. It mutates so much from one year to the next, frankly, from one minute to the next, flu is a moving target, that vaccination or natural infection the previous year doesn't protect you, hence the need for a yearly vaccine. Measles also is a single-stranded RNA virus. It also mutates. But we've had a measles vaccine since 1963, and that virus has never mutated away from the vaccine. I think the question for us with this particular virus, SARS-CoV-2, which is it going to be more like, is it going to be more like flu or more like measles? I suspect it'll be somewhere in between.

Unger: Interesting. Well, we learned more about the Johnson & Johnson vaccine last Friday. How should physicians be talking about efficacy to their patients when you have a spectrum of vaccine, or you might in the future, especially if Johnson & Johnson, for instance, their vaccine becomes another viable option? If given a choice, which type of vaccine would you prefer, an mRNA vaccine or the Johnson & Johnson candidate?

Dr. Offit: Whichever one I can get. I mean, right now, we're in a world where these vaccines are in limited, limited supply. I mean, now what's happened is we've gotten much better at administering these vaccines. Initially, if you recall, the percentage of vaccines that were administered versus distributed was 20%. Then we were 30%. Then we were 40%. Now, we're over 50%. And you have a lot of these mass vaccination clinics that are just standing back and saying, "We were just going to have to stop until we get more vaccine." We need more vaccines. So the Johnson & Johnson candidate, should it be approved through Emergency Use Authorization by the FDA's Vaccine Advisory Committee, on which I sit, and then the FDA itself, we'll see. I mean, right now, we're all looking at press release data. We haven't really seen all the data. We will see all those data when they're submitted, when the company actually submits for approval.

But for right now if you look at it, it appears to be highly effective at preventing severe disease. I mean, there were 40 to 60 cases of severe disease or fatal disease in that trial, and they were all in the placebo group. So, I mean, if you tell somebody, "Look, I have a vaccine that's going to keep you out of the hospital, keep you out of the ICU and keep you out of the morgue," do you want to get this one? Yes. I would think a lot of people would see this as a desirable product.

Unger: It's an interesting difference in the way that you're talking about it versus what I read in the mainstream press, that your focus here has been on that preventing of severe or possibly deadly cases of that, whereas what you read a lot about is just general effectiveness. How do you look at that?

Dr. Offit: That's a good point. I mean, it's when Moderna and Pfizer did their trials, they looked to show that they were at 95% effective against mild, moderate, to severe disease. And this Johnson & Johnson vaccine may not be as effective, again, I think we need to look at the data and see how people were defining things, may not have been as effective against mild disease, but that's a luxury. I mean, I think that if you have mild symptoms, the kind of symptom that's not going to bring you to medical attention, that's not going to make you go to the doctor, that is certainly not a burden on the health care system, which is really the goal here. I think it's we're being overwhelmed. The health care systems are overwhelmed, not only with this, but we're not able to take care of all the other things that require acute intensive care because of this virus. This virus is now the most common reason to die in the United States. I mean, it's exceeded things like heart disease and stroke, which is remarkable.

Unger: Well, this might be a moot question given your point, but if someone gets a Johnson & Johnson vaccine, assuming it's authorized, then they receive the Moderna or Pfizer vaccine at a later date once we have more supply, is that a rational approach?

Dr. Offit: So, again, you'd like to see the data, even just phase one data where you give the vaccine, give them the other vaccine, and see what happens in at least a few 100 people before you would make that kind of recommendation. But Johnson & Johnson is also in the midst of doing a two dose trial in the United States, so those data probably will be available sometime around April, in which case, then you'll see whether two doses is better than one for the Johnson & Johnson product had may then mimic what we see for Pfizer or Moderna. We'll just have to wait and see.

Unger: Very interesting. What other promising vaccines are in development, to your knowledge, and what do the timelines look like given that supply is a major issue right now?

Dr. Offit: Right. So China has a whole kill viral vaccine where you take the virus, grow it up, purify it and then kill it with a chemical, which is the way we make the inactivated polio vaccine or the Hepatitis A vaccine or the rabies vaccine. I haven't seen published data on that vaccine. I mean, you hear press release data that it's protective in the low 90% range. The advantage of that kind of vaccine is you would certainly expect it to be safe. Even though it requires more than one dose, you at least have commercial experience with that kind of vaccine. Russia just actually published a paper today in The Lancet. They have a two-dose strategy using replication defective human adenovirus type 26, followed by replication defective human adenovirus type five, which the 26 is exactly the same strategy that's being used by Johnson & Johnson.

The way that works is that you have a virus like adenovirus, which is really a common cold virus, that you then disable it so it can't possibly reproduce itself. So it serves as a trojan horse to bring into the cell the gene that codes for, in this case, the SARS-CoV-2 spike protein. It's in the form of DNA, so it's then transcribed to RNA. It then goes into the cytoplasm. And at this point, it's just like the messenger RNA vaccines. You have messenger RNA that's in the cytoplasm that codes for the coronavirus spike protein, so your body makes a spike protein, then your body makes antibodies to the spike protein. The data that were presented out of the Gamaleya Research Institute for this Russian vaccine called Sputnik five is based on those original sputniks that went into outer space, on which the movie "My Life as a Dog" was made, not that that's an important part for your crowd, but it's true, like what's the name of the dog in Sputnik two?

So, in any case, what they found was that it's roughly 92% effective, all age groups. It's highly effective against severe disease. There were 20 cases of severe disease on the placebo group. So if you trust those data, it looks good. Again, I can't imagine we would use that vaccine in this country until it was tested extensively in this country.

Unger: Okay. Well, there's been a plenty of debate about reopening schools. Much of the conversation on that front though has been about getting teachers vaccinated. Where do we stand on getting an authorized vaccine for children under 16? And are we closer? And will that be a game changer in your mind?

Dr. Offit: I'm not sure it'll be a game changer. I mean, I think that if you look at children regarding COVID-19 vaccine, I think the people less than 21 years of age make up about 26% of the United States population, yet they account for 0.08% of the deaths. So they're not the people that die. I mean, I work at the Children's Hospital of Philadelphia, we certainly have a COVID ward, but we're not nearly as overwhelmed by that virus as say our neighbor the Hospital of the University of Pennsylvania which takes care of adult patients is. So I don't see it as a game changer. Certainly, we'd like to get teachers vaccinated, but that said, I think, we're not helpless here. We still can wear masks, social distance. I think, there are countries like Denmark which have gotten their kids back to school. Frankly, in the Philadelphia community, the parochial schools are still in school.

I just think that I agree with teachers. I think that they are essential workers for society. We need kids to be back in school. Distanced learning is not the same as on-site learning. There's an increase in incidence of depression among school children. Certainly, for many school children to Philadelphia, that's the only decent meal they get during the day. Child abuse is often noted in school. We need to get kids back to school. And I think we can do that safely. I do think though that the goal is to mitigate risk. The minute you walk outside, you are taking some level of risk. The goal is to mitigate risk as much as you can. We're never going to completely eliminate risk and I just think that's a concept we need to get used to.

Unger: Excellent. All right. Well, as we know, and you've talked about before, supply and distribution have both been challenges in this rollout. How do you see the next few weeks and months playing out? Should we be thinking about end of summer is the goal for a large percentage of Americans to be completely vaccinated? What's the expectation that you would like to see set?

Dr. Offit: If you agree with Tony Fauci, and I do, that we need to get at least 70% of the population vaccinated, we have a population of 330 million people, so if you're talking about 70% of the population, that's about 240, 250 million people for a two-dose vaccine. That's roughly 500 million doses. If we give a million doses a day, then we're going to get to 500 million doses sometime in the middle of the end of next year. That's not acceptable. I think, right now, we're at about 1.35 million doses a day. We need to get to three million doses a day to really get us vaccinated by summer. And then there are other good things here, by the way. First of all, we'd have two excellent vaccines. That's good. I think we have two more vaccines, Johnson & Johnson and the AstraZeneca product, which may well get EUA approval, we'll see.

Also, the thing we never talk about is there are a lot of people in this country who already have been infected, who are likely to be immune when exposed to the virus again. I mean, the recorded number is 26 million, but that's just people who've been tested and found to be infected. Many people have been infected, but they've never been tested either because they're asymptomatically infected or mildly symptomatically infected, or they've tried to get tested and couldn't get it done. So how many people is that? When you do antibody surveillance studies to see how many people really have been infected in this country, you realize that, that 26 million number is probably off by a factor of at least three. So probably between 75, 80, as many as 90 million people in this country may already have been infected, which is 20% to 30% of the population that's essentially immune.

So we already have that base that we're working with, and then we'll continue to vaccinate people. We're already at more than six million people who have already gotten two doses of vaccine. I predict that things are just going to get better over the next six months, despite what you hear when you watch television. You have two doses with more coming. You have an administration is clearly committed to getting this done. You have a large number, a fairly large percentage of populations already immune, because they've been naturally infected. And the weather will get warmer, which makes it more and more difficult for this virus to spread. So I see over the next four or five, six months, I see the number of cases, the number of hospitalizations, the number of deaths coming down.

Unger: Excellent. Do you think the bottleneck is going to be on the supply or the distribution side, or do you just see concomitant progress on both ends?

Dr. Offit: I think we're certainly getting better on the administration side. I mean, we've gone from 20% to 30% to 40%, to now more than 50% of distributed vaccines administered as we've gotten better and better at mass vaccination. So that's good. I think right now the biggest promise is production, mass production, of getting the vaccine out there. I think if we can make it, we can distribute it, and if we can distribute it, we can administer it, but we need to make it.

Unger: So longer term, and you referenced this at the beginning of our interview, do you see COVID vaccines following the same path that we see with flu vaccines where there's some reformulation every season and we get a shot annually? Or is this more like a long term immunity thing that might be achievable?

Dr. Offit: I think if you look at the immune data associated with two doses of vaccine, I want to emphasize how important it is to get two doses of these vaccines, I think that we will have immunological memory, which is to say that for a virus like this, which has an incubation period, meaning from the time when you're exposed to the time when you develop symptoms of it, at least around six days, that's plenty of time for activation and differentiation of memory cells to become effector cells, meaning antibody producing cells. So I think the vaccine could be effective for years. A few years, not decades, probably, but certainly for two, three years. I think that's possible. So the only reason to give another dose the following years is for like flu, that the viruses have mutated so much that your previous immunization does protect you.

That would surprise me. We're certainly not there yet. I mean, look for those people who've been immunized, who are then still getting admitted to the hospital with severe disease. When you start to see that happening, that's when you worry. But for right now, for all the fear of these variants, that hasn't happened yet. It may well happen, but it hasn't happened yet.

Unger: Well, thank you so much, Dr. Offit. I learned a lot today. I think our viewers will too. Appreciate your perspective. That's it for today's COVID-19 Update. We'll be back soon with another update. For resources on COVID-19 visit ama-assn.org/COVID-19. Thanks for joining us and please take.


Disclaimer: The viewpoints expressed in this video are those of the participants and/or do not necessarily reflect the views and policies of the AMA.

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