COVID-19 Updates

Breaking down COVID-19 vaccine booster approvals

In this Mayo Clinic Q&A podcast, Dr. Poland talks about the approval process for COVID-19 vaccine boosters, including for the Moderna and J&J COVID-19 vaccines, as well as the possibility of emergency use approval for children, down to age 5, before the end of October.
October 13, 2021
Guest: Gregory A. Poland, MD l Host: Halena M. Gazelka, MD


Dr. Halena M. Gazelka: Tell us, Greg, about what was the path? How did all this come down, and what is the answer now about boosters? 

Dr. Greg Poland: The FDA Advisory Committee was confronted after hearing the data with the question: do the safety and effectiveness data support approval of the dose, a booster dose, six months or more after the primary Pfizer series in people 16 and older? So everything we're about to talk about is limited to the narrow case of Pfizer, and they voted 16 No, three Yes, so that was defeated. 


They then revised the voting question: what about a booster dose at six or more months and people age 65 and older and at high risk of severe disease? They voted 100 percent yes on that. Then a third vote, which was: should health care providers and others at high risk for occupational exposure be included? The vote was 100 percent yes. 

Now, what happened is that, this past Wednesday and Thursday, as per protocol, it went from the FDA Advisory Committee to the CDC Advisory Committee, called the ACIP: Advisory Committee on Immunization Practices. I have been a past member of both of these committees, so I know how they work well. 


So again, after hearing the data for a day and a half, they then voted. The first question was, and again, this is only for Pfizer vaccine: should there be booster doses for people age 65 and older or in long-term care facilities six months or more after the primary series? And it was a unanimous yes. Now, that was a should recommendation, it should be offered. 


The second vote was in people 50 to 64, so they've stepped it down one age range who have medical conditions, and the vote there was 13 yes to no. And again, that was a should recommendation. It should be recommended. 


Now, two more votes. The third vote was what about 18 to 49-year-old who have medical conditions, basing that on their individual risk and benefit. And that was nine yes, six no. It was very close vote. That one was different because now you're in the situation and CDC will have to do this very carefully of defining what medical conditions, what would be the individual risk and benefit parameters that a clinician would take into effect. 


Then the final one should 18 to 64-year-olds with occupational and high occupational risk or in an institutional setting that was high risk be offered the vaccine. It was six yes, nine no. So that did not pass. Now, what happened? That was the vote that took place last Thursday. 

On Monday, the CDC director overruled that last vote and approved boosters for 18 to 64-year-olds who are at risk of exposure and transmission because of their occupational or institutional setting. So, that now is being operationalized. The key thing here is that they're going to have to make clear to the public, to the providers, who is at risk? This is a confusing set of recommendations because there have been pro and con votes, one has been added or changed. We're looking at a total of four. So we can kind of make it easy if you got as a primary series, the Pfizer vaccine. OK, that's all we're talking about is Pfizer. 


I know a lot of people are going and getting their booster (they call it freelancing). So I think we have solved the booster issue. Implementation is going to be a challenge. One note, we do not know how long the durability of the booster dose will be, by definition. We just started doing it. 

We also don't know what would happen with a new variant. And many people think that the need for the booster has been based primarily on time since the completion of the primary series, with some effect due to the Delta variant. 


Dr. Halena M. Gazelka: OK, so that's fine for people who had the Pfizer vaccine. But what about people who had Moderna and J&J? What happens to them if they want to booster?

Dr. Greg Poland: It’s a more complicated situation. The reason that they could approve, or if you will expand the Pfizer new way, is because they were the first ones out of the gate who had collected data on this. Both Moderna and JNJ are doing the same thing, but are a bit behind. So what do we know about the J&J vaccine? Well, we don't have a peer-reviewed publication yet. We only have a press release from the company showing that vaccine efficacy went up to 94 percent after a second dose. Globally, that same vaccine efficacy after a second dose was only 75 percent. Unclear why. 

The follow-up for that was only between one month and two months, so again, not a long amount of durability data. For Moderna, that's interesting, both because the dose is almost a little more than three times higher, and there was a week longer between doses and probably some minor differences in the lipid nanoparticle efficacy for the Moderna vaccine has been and persists, being higher than J&J or Pfizer. 

What will be the long-term meaning of that? Again, by definition, we don't know yet. What we can say is there was just released a paper in JAMA looking at a Pfizer booster in those who had gotten the Moderna vaccine and those who had gotten the Pfizer vaccine. 


If you look in people over the age of 50 who got a Moderna primary and Pfizer boost, their antibody level was almost 72 in the way this was measured. If you look at people who got a Pfizer primary series and a Pfizer boost – and again were over the age of 50 – their antibody level was still less than half that of Moderna, only 31. 

Now, what is the clinical meaning of that? It's hard to know at this point. And – I've just given you a very quick run over the data – it's led to a lot of confusion. More confusing? Yeah. More is not necessarily better. Might more mean efficacy for a longer period of time? Yes, maybe. But our way out of this as Dr. Walensky at the CDC said, and I agree with it, “We cannot boost our way out of this pandemic.” 

This is a chasing-our-tail kind of scenario until we get the large proportion of Americans who are eligible for vaccines, vaccinated. The biggest fear we have is that we're going to continue to generate variants that will increasingly learn how to escape immunity. We've seen that with the Delta variant. There's another variant called the R1 variant that has kind of disappeared from the U.S., interestingly enough. But all of these are possibilities. 


Dr. Halena M. Gazelka: So, Greg, one thing I wish you would clear up for me is I have difficulty with what is the difference between a third dose and a booster? Are you getting the same medication, the same vaccine, or is a third dose different than what you'd get in a booster? 

Dr. Greg Poland: No, there they are identical. And again, that terminology, I agree, has led to some confusion. So a late dose, a late third dose is terminology restricted to those who are moderate to severely immunocompromised. They need a three-dose, if you will, primary series, whereas you and I got a two-dose series. A booster dose is something that occurs after the primary series. It is a true boost. 

So it may well turn out that the moderately to severely immunocompromised who got three doses will also have to get what, in essence, is a fourth dose of their booster. Whereas you and I would get a third dose, one booster. And it's the same dose, it's the same vaccine. 


Dr. Halena M. Gazelka: OK. Makes sense. Greg, tell us about the latest with kids in vaccines. 

Dr. Greg Poland: Yeah, this is good news, and I'm pleased to share this. It turns out that the manufacturers have been able to enroll children faster than they thought and collect the data, even though they expanded the size of the study. 

So there is thinking that prior to Halloween, we will see EUA approval for children down to the age of five. So 5 to 11 years old, we already have the EUA for 12 and above. Now it will be a dose of Pfizer vaccine that is 10 micrograms, rather than the 30 micrograms that many of us would have got, so a third the dose. 

Now what they're working on is people six months to four years old who will get a tenth of the dose instead of 30 micrograms. They'll get 3 micrograms, and the studies show it's safe, it's effective, and those younger kids, no surprise with those much lower doses, generate antibody responses equal to people in that 12 to 18-year-old age group. So I think the good news is that we're going to see that become available now. Here's my prediction. 

Dr. Halena M. Gazelka: You heard it here first. 

Dr. Greg Poland: We're going to see, and we are already starting to see, a trend I've been able to follow for over a week or two now of slowly declining cases. If people use masks and responsible distancing, if there's no new variant, I expect that trend to continue. 

What I'm afraid is going to happen is, just like last year, we'll get to mid-winter and have another surge. But that decline is going to fool people into thinking there's no more risk just as the vaccine for kids will be coming out, and people will say, “But we don't need it.” That will fuel a mid-winter surge. 


Dr. Halena M. Gazelka: Greg, continuing on the theme of kids and vaccines, we have had a number of listeners ask us the very same question. They have understood that the Moderna vaccine might be more effective against some of the variants, and they're wondering, even though Pfizer is likely to get an emergency use authorization for children the fastest, should they have their child get the Pfizer vaccine or should they wait? 

Dr. Greg Poland: I'm going to continue what we said from the very beginning. The best vaccine to get is the vaccine available to you. And I say that, particularly in the case of kids. Why are we even immunizing children? A valid question because they tend not to die now. Now, there have been, in fact, over 500 deaths. They tend not to be hospitalized, though, with Delta. 

We've seen over 20,000 hospitalizations, but at the population level for kids, that is still at least an uncommon event. So we're trying to prevent that uncommon event. We're trying to prevent them from spreading it to other people while keeping them in school and social activities. That's the conglomeration of reasons why we would immunize kids. 

So if I had a child that was five, eight years old, as soon as that EUA was available, I would have them immunized with the Pfizer vaccine. Rather than waiting for an unknown amount of time until Moderna presented data to FDA. I might have a slightly different feeling if I had a highly immunocompromised child or if it was an older adult. But for the younger children, we're not as worried about whether they're going to have severe disease or be hospitalized. We're trying to prevent them from having any disease spread, and we want to keep them in school. 

Dr. Halena M. Gazelka: Makes sense. Greg, there's ongoing research for an antiviral medication to help treat COVID. Do you think that, sometime, we're going to have a pill that people could take to treat COVID? 


Dr. Greg Poland: I think I think the odds that we will have it are very, very high. Merck, in particular, is quite advanced in the development of an oral antiviral called molnupiravir. They always have these long names, yes. Roche and Pfizer have also engaged in phase two/three studies of an antiviral, and the thought is much like we treat influenza with an oral medication. 

In fact, influenza has advanced to the point where you take one pill once. To treat an influenza infection, that's an amazing feat of science. And so the landscape going forward with COVID, I would say is rosy. If this large number of unvaccinated people will get on board, otherwise, my concern is we will continue to see the development of new variants and mutants, some of which have already learned how to evade monoclonal antibodies. So it's a serious issue. 

But if we can solve that issue, what I see is that we'll give a coronavirus vaccine, let's say, annually with the flu vaccine. If somebody didn't get it at breakthrough disease, or whatever, I think we'll probably be treating it with an oral antiviral. And I think as time goes on, we're going to see second and third-generation coronavirus vaccines. In particular, there is the potential for an oral vaccine like taking a pill for your vaccine or a nasal spray or a Band-Aid-like patch to administer the vaccine. So I'm very enthusiastic about that. I think the science is heading in that direction, and maybe that will prove to be more acceptable to people who are otherwise hesitant. 

Dr. Halena M. Gazelka: Greg, I'm smiling because you use the word rosy. The outlook is rosy, and I think that's the first time I've heard you say that. It's probably right in a very, very long time. So I felt like we should just stop there while we were ahead with it to 

Dr. Greg Poland: Celebrate that word choice. That's right. 

Dr. Halena M. Gazelka: Tell us you got anything else to share with us today. 

Dr. Greg Poland: I do. We were talking about school, so I thought I would do a show and tell.  


Dr. Greg Poland: We're seeing all kinds of things – people using hydrogen peroxide, including young kids, nebulizing it, swallowing it, gargling it. No. We're seeing people send me this stuff. 

We're seeing people taking high doses of vitamin D and a variety of other repurposed drugs. No data for that. Home remedies that people are using this are cedar shavings in a bottle that you open and sniff, and somehow it wards Covid away. No. 

I find all kinds of pastes, including ivermectin. No. So what does work? Well, what does work is vaccines. We've clearly seen the data in multiple studies across multiple countries over time and mass. The data are clear. Once you get COVID, these other things that I've shown you are not treatments. They're magical thinking, they're not treatments. 

There are valid treatments for COVID monoclonal antibodies, antivirals that are readily available. But as we always say in medicine, prevention is much easier than trying to cure. I would much rather have you suffer an hour or two of arm discomfort and maybe a headache and low-grade fever for a couple of hours and be protected than to see you every day in the hospital with it. Us struggling with whether you need to go on oxygen or not, treating you with a variety of medications, you losing school work time, maybe suffering a complication, maybe having long-term COVID when all of that is unnecessary. 


Dr. Halena M. Gazelka: Well, those are some true words of wisdom. Thank you, Greg. I have never ceased to be amazed by the willingness that some individuals have to use what they read about on the internet or that otherwise might be unproven or even unsafe. 

Dr. Greg Poland: This started early on. People are still gurgling and even swallowing bleach. I didn't have a bottle of that to show. Please do not do that. And the irony I face – it keeps me up at night because I get emails from people from all over the world – they will reject a vaccine that has been studied this intensely and then use treatments for which there are no scientific data. 

I mean, it boggles the mind to understand what tipped you into an unregulated treatment where we have no safety or efficacy data. It doesn't make any real sense.

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