The science behind booster shots

Federal health officials recently announced that COVID-19 booster shots will be available to adults in the U.S. in September. Corey Casper is the CEO of the Infectious Disease Research Institute and a professor of medicine and global health at the University of Washington. He joins us to tell us more about the science behind booster shots.

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Note: This transcript was computer generated and edited by a volunteer

Dave Miller: This is Think out Loud on OPB. I’m Dave Miller. Last week, the Biden administration announced that fully vaccinated adults in the U.S. who received two doses of either the Pfizer or Moderna vaccines will be able to receive a third shot, eight months after they were initially vaccinated. The idea behind these extra doses is to increase protection against COVID-19. The booster shots could be available starting next month. Meanwhile, in huge swaths of the world, most people have not gotten a single dose yet, let alone one booster or a second booster. We’re going to talk about all this now with Corey Casper. He’s the CEO of the Infectious Disease Research Institute and a professor of medicine and global health at the University of Washington. Corey Casper, welcome back to the show.

Corey Casper: Nice to be here. Thanks for having me.

Miller: Let’s start with the science, and then we can turn to the policies and the ethics. Why is it that immune protection from COVID-19 vaccines is reduced over time?

Casper: First it’s really important to remember that there are many different types of vaccines against SARS-CoV-2. They all work in different ways, which means that they trigger different types of immune responses and frankly it may last different amounts of time. But what we do know is for the vaccines that are currently used under emergency use in the United States– the protection wanes. We’ve known this for some time based on models, but now we know it from the experience that we can follow levels of antibodies in people who have received the vaccine. What you see is that after the course of vaccines has been completed, you get a very high level of antibodies that protect you against this virus. Those antibodies begin to decline over time. And what we now know is that probably about six to eight months after you’ve received the last dose of your vaccine, the level of those antibodies may not be sufficient to protect you from infection.

Miller: Is this different from the way other kinds vaccines or natural immunity works, that if a body isn’t exposed to some particular pathogen after a while, it stops making as many antibodies for that virus?

Casper: Yes, it’s hard to generalize, but overall that’s correct. What we know is that it differs by the type of vaccine or the type of natural infection. Maybe on one side of the spectrum would be diseases like measles or like chicken pox, where a very strong and broad immune response is elicited either by natural infection or vaccination, and protection can be lifelong. On the other hand, we’re all very used to seasonal flu vaccines and influenza vaccines that really only last a few months. It depends on the type of infection and on the type of vaccine, but generally the concept is that most vaccines have a duration of immunity. Unfortunately for these covid vaccines, that duration is about six to eight months.

Miller: Is it fair to say that we would be having perhaps a similar conversation today, even if it weren’t for the Delta variant?

Casper: That is absolutely correct. We likely would be facing a waning immunity to our vaccine even in the absence of variants of concern. Unfortunately, the variants of concern– the Delta variant, the Lambda variant, and even new variants that are predicted to be emerging– are less susceptible to the current vaccines. That means they require higher levels of antibody to maintain that same degree of protection. That means it’s a shorter amount of time that you are protected from these variants of concern after your primary vaccination series.

Miller: You mentioned the two ends of the spectrum in terms of the duration of immune response, with measles at one end and, say, the flu– where many of us take yearly flu vaccines– at the other. Is it a given for you that going forward there will be yearly COVID vaccine booster shots the way there are for the flu?

Casper: No, it’s not a given at all. If we choose to address this pandemic in a holistic fashion. What I mean by that is that we are in an unprecedented new age of vaccinology. We have the technology, I believe, to make what I would call a “universal booster,” and one that could be a durable booster, that could last maybe a decade or more. But we need to make investments in these new vaccine technologies rather than rest on the successes that we had in the first phase of this pandemic.

Miller: Can you help us understand what that means? I thought the mRNA vaccines, which had been in development for many years but not globally deployed like they have been now, as a novel vaccine technology. It seems like you’re talking about something altogether different?

Casper: In some ways, yes, in some ways, no. The whole field of vaccinology has taken leaps and bounds over the last 10 years. RNA vaccines, [we’ve all become] familiar with them really just over the last year with Covid, but they’ve been in development for some time. But there’s been many other technologies that have also been brought forward. I’ve talked before about these immune stimulating molecules known as adjuvants which increase the strength, breath and duration of immune responses. We now know that the Johnson & Johnson vaccine is based on an Adenovirus Vector. All of these different technologies are incredibly exciting. Data that I’ve seen– some generated here and some elsewhere– [shows] that many of these strategies can lead to a broader and more durable protection. As a few examples, one thing we now know is that you can mix and match vaccines. We’re encouraging individuals to not do this on their own. But in the controlled setting of clinical trials, we’ve seen that when you combine two different types of vaccines, let’s say an adenovirus vaccine and an RNA vaccine, you get a much broader and longer lasting response,

Miller: Meaning if you got the Johnson & Johnson vaccine for your first dose and then the booster a couple weeks later of Moderna– would that be an example of what you’re talking about?

Casper: That’s exactly right. The scientific term for that is a mouthful. It’s called a heterologous prime boost. It means that the first and second doses of the vaccine you got are not the same. And so what you just cited as an example has been shown in small studies to lead to broader and more durable protection. What’s very interesting is that the sequence of the vaccine seems to make a difference which you get first and some are more synergistic than others. I’ve had patients, friends, [and] family ask me if they got [the] Moderna vaccine, should they now run out and get the Johnson & Johnson or vice versa. And I would say that this isn’t something that we should do at the level of an individual experimenting. We really need to see the data from clinical trials. But the preliminary data that we’ve seen [is] quite exciting. That’s one example of an approach that will lead to a longer lasting response against a broader swath of coronaviruses. Similarly, a few months ago we published data that showed that when you give one of these immune stimulating adjuvants with a protein against COVID, we were able to protect against all of the coronavirus families that we tested– the original SARS-CoV-1, MERS, and all of the variants of concern that we looked at. That approach– using these immune stimulating molecules– is also one that we’re proceeding quickly with developing. But at this point, none of those technologies are available to people who [were] vaccinated early in the pandemic.

Miller: Do you think that pharmaceutical companies have as much of an incentive to create a vaccine technology that would provide protection for a decade or more if they can make money by selling us on doses that we have to have at least once a year?

Casper: Yeah, I hate to be so cynical, but I think there’s a lot of truth to what you just said. Vaccines were long considered to be a very unprofitable arm– all puns intended– of the pharmaceutical industry. The better ones were given either once in your lifetime, or once every 10 years, or even just once a year. The way that pharmaceutical companies are moving right now, they’re preferring medications that are chronic– things that you need to take every day or that are very expensive, like cancer therapeutics, because of the return of life received by those products. They can charge such a high amount for them. Vaccines have long been thought to be unprofitable. If anyone is looking at the profit and loss statements of Moderna and Pfizer, you can see that vaccines can be very profitable, especially when subsidized by the government. But yes, I would say that there’s a disincentive to vaccines that are longer lasting or even just to develop new vaccine technology, which is extremely expensive.

Miller: We got a question from Gabriel Cavatorta on our Facebook page. He says, “I gather each vaccine manufacturer will be using the same vaccine formulation for the booster shots as for the first two doses. Is this indeed the case? Will the formulation be adapted to provide better protection against the now dominant Delta variant anytime soon? And one more question, how long will it take for an updated version of the vaccine to get full FDA approval?”

Casper: Great, great questions, exactly the ones we should be asking. Right now the strategy that is being pursued is to give a third dose, and I say a third because really this is only being recommended with the two RNA vaccines. A third dose ideally of the same vaccine that you got before. So if you’ve got two doses of Moderna you’d get a third dose of Moderna. I will say that in development right now and in testing, Moderna has made a delta virus variant specific booster. Unfortunately, that’s just finishing phase two trials now. It will be some time until you see the results of the phase three studies, and until it’s approved to be used more broadly. Unfortunately we’re chasing our tail a little bit or we’re lagging behind the virus. The virus is running way past us and how quickly we can manufacture and test these new constructs. That being said, there are a number of different vaccine manufacturers right now and developers who are looking at different approaches like a universal approach that I’m very excited about. The problem is that it just takes a long time for the testing and approval.

Miller: Let’s turn to ethics. How do you personally reckon with this policy in the U.S. and Israel and other rich developed countries that will give many people, in the richest countries on earth, third vaccine doses before–I think the number is billions– of people in poor countries around the world have gotten a single dose?

Casper: This is a really hard question to wrestle with. We are under the illusion right now that there’s even any equity in how these vaccines are being distributed. And the statistics that you pointed to are quite striking. About five percent of the billion people in Sub-Saharan Africa have been vaccinated against COVID. Right now there is really not equity in the way that this vaccine is being distributed across the world. The booster policy here in the United States and in other wealthy countries will only exacerbate that inequity by taking those doses that could be repurposed for other settings and reapply them back here in the United States. The way I’ve sort of reconciled this is that we need to come to the conclusion that vaccine production and distribution really has to be a local endeavor. Every country or every region is going to be fighting to protect themselves first, and the countries that are richest or that make these vaccines will always have first access to them. We and others have been working very hard to develop strategies by which these vaccines are made locally or regionally and they can then be prioritized and distributed locally and regionally. But until that happens, it’s a fallacy to think that there’s much equity in this vaccine distribution. That being said, the United States has entered these long term contracts with vaccine producers to have additional doses of vaccine available. We have more vaccine that we need here in the United States. On one hand, you could say that we should just begin to ship those around the world. And certainly I think that that is possible. There are logistical issues like cold chain and others that make that complicated. Given the way that these contracts are set up, if a third dose is needed to protect high risk individuals, I would say really the highest risk individuals should be those prioritized. I can see an ethical argument where that would be okay.

Miller: The premise of my question and of your response is a kind of global selflessness– is it right? Is it moral for us to grab all these things when other people have nothing? But is it possible to look at the same question from a more selfish lens and to say that the more people around the world have gotten there first or their second doses, the less likely it is that a variant worse than delta will emerge somewhere in the world and sweep the world the way Delta did?

Casper: One hundred percent. The concept we miss here in the United States is that until everyone on this planet is protected, none of us are protected. What we saw with the Delta variant is that [it] emerged from places where there [were] low rates of vaccination, and it really ran rampant. You’re exactly right. Unfortunately that applies to us here in the United States as well. There are huge segments of our population that have not been vaccinated, and those segments of the population put us at great risk for brewing new variants of concern.

Miller: The delta variant has basically taken over the world, but there are more Greek letters in the alphabet. What variants are you paying attention to right now?

Casper: Obviously the lambda variant is one that has been recently identified and a reduced protection from our current vaccines has been predicted. I recently saw some very preliminary data on new variants of concern from Sub-Saharan Africa where there are additional mutations that we right now can just predict will also make these vaccines less effective. The reason I’m concerned is we have the perfect setup for breeding viruses that are resistant to our vaccines and that’s a twofold situation. One you just alluded to which is that there are huge parts of the world where people are completely susceptible and therefore can get bad infections where you grow the virus in a person and it can mutate and be transmitted. What worries me is that what we now know in the United States is even if you’ve been vaccinated against COVID, you can incubate and replicate these variants, or even perhaps the native virus, in your nose, because we have incomplete immunity in the nose in someone who’s been vaccinated fully against covid. That’s a recipe for breeding variants where you have the virus replicating in the nose under no real immune pressure and then can be immediately transmitted to others because of its proximity to the respiratory tract.

Miller: What [does] the next year look like to you? Not what do you hope it’s going to be, but what are you actually expecting?

Casper: I hate to be such a naysayer, but I cannot see a situation in which in the next several months we wouldn’t meet the criteria for another series of broad and significant lockdowns. I don’t know whether or not our public or our politicians will have the will or the fortitude to enforce those. But in terms of the epidemiologic necessity, I see a much worse situation emerging and that worries me very much. We could mitigate that if we could rapidly vaccinate the swaths of people who are not currently vaccinated. But that would be both here and around the world. What we really need to do right now is prioritize that, and prioritize the development of more effective, universal durable boosters.