How Long Does COVID Immunity Last Anyway? : Short Wave With booster shots on the horizon for some people, one of the biggest questions is: Am I still protected against COVID-19 if I've only had two doses of the vaccine? As science correspondent Michaeleen Doucleff reports, the answer is...complicated.

Read more of Michaeleen's reporting on COVID immunity: https://n.pr/2XIQ6KX

Reach the show by emailing shortwave@npr.org.

How Long Does COVID Immunity Last Anyway?

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MADDIE SOFIA, HOST:

You're listening to SHORT WAVE from NPR.

EMILY KWONG, BYLINE: Hey. Emily Kwong here with science correspondent Michaeleen Doucleff.

MICHAELEEN DOUCLEFF, BYLINE: Hi, Emily.

KWONG: Hey. You're here to talk about a question that a lot of people have had about the COVID vaccine - myself included - but no one really knows the answer to it. How long does immunity last?

DOUCLEFF: Totally. This is the question. And it is super complicated. I mean, there's a huge debate about boosters.

KWONG: Right. I mean, the Biden administration and the FDA are discussing this right now, whether people - and if so, who? - should receive a booster shot about eight months after their original vaccine. Some scientists advising the White House say that the effectiveness of the original vaccine is waning.

DOUCLEFF: Yeah. But many, many scientists I talked to, Emily, say, not so fast. Is that really necessary? They don't agree at all with the administration's call for boosters for most adults because they say the science just isn't there. You know, recent studies have actually shown the opposite, that eight months after the vaccine, your body actually may be better prepared to fight an infection, better able to handle it.

KWONG: This is what I've heard. How is that possible?

DOUCLEFF: OK. So right after you get a vaccine, your immune system starts to make a lot of antibodies in a big burst, which can prevent an infection, right? But that high level of antibodies, it doesn't last very long. About a month after you get vaccinated, they start to disappear. Deepta Bhattacharya is an immunologist at the University of Arizona.

DEEPTA BHATTACHARYA: Every single immune response, there is a sharp rise in antibodies. And there's a period of sharp decline.

DOUCLEFF: But, Bhattacharya says, that's totally expected. It happens after every vaccine you get, no matter if it's for the flu, the measles, whatever. And actually, Bhattacharya says, the antibodies don't decline forever. They stick around and stabilize at a lower level. And guess what, Emily.

KWONG: What?

DOUCLEFF: The antibodies that are left over are, in many ways, better than the original ones. They are more powerful - I'm talking much more powerful. They are better able to stick to and neutralize the virus.

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BHATTACHARYA: The quality of the antibodies improves. And so it takes far fewer of those antibodies to protect you. So think, like, worrying about antibody decline is not something that's productive.

DOUCLEFF: And that's not the only way they've changed. There's other remarkable ways that are preparing your body for a future encounter, not just with delta, but even future variants.

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KWONG: So today on the show, a pulse check of your COVID antibodies, what happens to them months after a vaccine and why some people may even have an exceptionally strong immune response. I'm Emily Kwong.

DOUCLEFF: I'm Michaeleen Doucleff.

KWONG: And you're listening to SHORT WAVE, the daily science podcast from NPR.

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KWONG: All right. Michaeleen, you're telling me that even though the antibody count goes down over time after you get the COVID vaccine, the antibodies that remain are, like, low-key powerful? But how exactly are they still powerful?

DOUCLEFF: OK. So there are two ways to think about it. You can think about it as they're more durable, and they're more flexible.

KWONG: OK. What does that mean?

DOUCLEFF: All right. Let's tackle the first one, durability, OK? It's the easiest. Scientists think these antibodies will likely stay in your blood and your body for a very long time, like decades, even maybe your lifetime. And so they could give you long-term protection against severe COVID because the cells that create these antibodies do something remarkable. Immunologist Ali Ellebedy and his colleagues at Washington University of St. Louis have just completed studies showing that several months after the vaccine, these cells migrate into the bone marrow and stay there.

ALI ELLEBEDY: The cells go to the bone marrow. And they become eternal.

DOUCLEFF: So they're immortal?

ELLEBEDY: They are. They live for us for the rest of our lives.

DOUCLEFF: Wow. And the vaccine can do that?

ELLEBEDY: And the vaccine can do that.

DOUCLEFF: And, Emily, the immune system doesn't stop there. While it's making these more powerful antibodies, it's also training up other cells, cells that patrol around your respiratory tract looking for SARS-CoV-2 infections.

ELLEBEDY: It's almost like going to neighborhood house by house and...

DOUCLEFF: Knocking on doors.

ELLEBEDY: Yes, just making sure it's clean, there is no virus inside.

DOUCLEFF: These cells are called T cells. And, you know, they kind of hunt for infections.

KWONG: Right, like if they find an infected cell in your nose or throat.

DOUCLEFF: Or in your lungs. And then they literally kill that infected cell and clear it out (laughter).

KWONG: Yeah, big fan of T cells on this podcast. So let's say...

DOUCLEFF: Who is not a big fan of T cells (laughter)?

KWONG: It's true. It's true. It's true. Let's say you are vaccinated.

DOUCLEFF: OK.

KWONG: OK. You're healthy, so not immunocompromised. And eight months later, boom, you get exposed to the delta variant. What happens then?

DOUCLEFF: OK. So I talked with Jennifer Gommerman at the University of Toronto. She's an immunologist there.

KWONG: OK.

DOUCLEFF: She says, at this point, the level of antibodies in your body have waned, right? So if you get a big dose of the virus in your nose, the antibodies might get overwhelmed and won't be able to stop the virus from entering cells.

KWONG: And this is how we get breakthrough infections.

DOUCLEFF: Exactly.

JENNIFER GOMMERMAN: There is more symptomatic infection happening as we go further out following the vaccination rollout. So this waning antibody response is having an impact.

DOUCLEFF: But remember, your immune system isn't starting from scratch. In fact, it's been training cells and antibodies for months to detect the virus and kill it, to clear away cells infected with SARS-CoV-2.

GOMMERMAN: But you still have all the immunity inside of your body that will then say, OK, we've had a breach. And it's time to bring in the cellular immunity and respond to this threat. And because of vaccination, you have cells that can do that really quickly.

KWONG: Right. And while a breakthrough infection can knock you flat on your butt for a few days, most of them don't cause severe disease or land you in the hospital because you've got these antibodies from getting vaccinated.

DOUCLEFF: Absolutely. If you're healthy, under age 75 and not immunocompromised, the vaccines offer about 90% protection against severe disease. So your chances of ending up with a severe course of COVID or in the hospital is very, very low.

KWONG: Yeah. Michaeleen, antibodies that last decades sound amazing.

DOUCLEFF: Yeah.

KWONG: But you and I both know SARS-CoV-2 is crafty. It's more crafty than scientists originally thought. And over the past year, we've seen it mutate and evolve in ways that allow it to avoid detection by antibodies. So does that mean that eventually we'll need vaccines for different variants that crop up, like what we do with the flu?

DOUCLEFF: A few months ago, that's what many scientists thought would be the case.

KWONG: Right. Yeah.

DOUCLEFF: And to be honest, that's what I thought, too. And then this summer, some incredible research started to come out, started to shift the thinking because this research shows that the mRNA vaccines we have can actually trigger the immune system to fight off not just the original version of SARS-CoV-2 or just the delta variant, but also protect people from any variant circulating, as well as future variants.

KWONG: That's a big deal. I mean, who figured that out?

DOUCLEFF: It is a really big deal. So a big chunk of this research has actually been performed at Rockefeller University by a virologist named Theodora Hatziioannou. She studied HIV for about 20 years. And when COVID hit, she shifted her focus. For about the last year and a half or so, she's been following, with excruciating detail, how the immune system learns to protect a person from COVID. Specifically, what happens to individual antibodies in a person's blood after an exposure?

THEODORA HATZIIOANNOU: It's extremely laborious work. And it's extremely difficult to do. You can't do it with a lot of patients.

DOUCLEFF: You know, she and her colleagues have been following about 60 people throughout the pandemic.

KWONG: Wow.

DOUCLEFF: And there's lots of other research going on like it. And earlier this year, Hatziioannou started to notice something really surprising. After getting vaccinated, some people in this group she's following mount this exceptionally potent response to mRNA vaccines.

HATZIIOANNOU: Those people have amazing responses.

DOUCLEFF: She says they generate high levels of antibodies.

HATZIIOANNOU: They're the best, I mean, unusually high.

DOUCLEFF: But - and here's the key.

KWONG: OK.

DOUCLEFF: It's the type of antibodies they make which gives them an exceptional response. They're more powerful because they're more flexible, more diverse. They both recognize and kill the original version of SARS-CoV-2 and all the variants they tested, including delta. And they can also kill other SARS-like viruses, ones found in bats and pangolins.

HATZIIOANNOU: These people even neutralize SARS-CoV, the first coronavirus that came 20 years ago...

KWONG: Whoa.

HATZIIOANNOU: ...Which is very, very different.

KWONG: That's amazing.

DOUCLEFF: (Laughter) It is. I mean, to be honest, when I saw this research, I kind of didn't believe it at first. It's really incredible. And I have to say, it kind of is giving me the first glimmer of hope that the immune system is going to have an edge over COVID.

KWONG: Who is capable of mounting this immune response?

DOUCLEFF: Yeah. So I talked to Paul Bieniasz. He's also at Rockefeller University and helped lead these studies. So far, they've seen it in people with a very specific history.

PAUL BIENIASZ: Individuals who were infected early in the pandemic and then sort of between six and 12 months later, they were then vaccinated.

KWONG: OK.

DOUCLEFF: So he's talking about people who got sick last year, and then received a Pfizer or a Moderna vaccine this year. Bieniasz says that the natural infection is critical to this immunity because the virus may stick around in the body long after exposure.

BIENIASZ: While SARS-CoV-2 infection itself is thought to be quite short-lived, it is likely that some viral proteins, and possibly even some infected cells, persist, perhaps even for months.

DOUCLEFF: So this may give the immune system extra time to optimize and diversify its antibodies. So the antibodies can recognize all sorts of variants. Then, upon vaccination, these antibodies get boosted to a high level.

BIENIASZ: One could reasonably predict that these individuals would be quite well-protected against most and, perhaps, all of the SARS-CoV-2 variants that we are likely to see in the foreseeable future.

KWONG: That's powerful stuff. But we don't want people foregoing the vaccine just to get naturally infected and get antibodies that way, right?

DOUCLEFF: Oh, absolutely not. We do not want that at all, you know? Vaccines are by far the best tool we have to keep people out of the hospital, to keep people alive. There's growing evidence that when you get vaccinated, you also protect the people around you. And so John Wherry, this immunologist at the University of Pennsylvania, says there's evidence that you don't need a natural infection to get this impressive immune response.

JOHN WHERRY: We see some of it happening just in vaccinated individuals.

DOUCLEFF: His lab's research shows that months after the vaccine - just the vaccine - a person's antibodies begin to become more powerful, more flexible.

WHERRY: So the same antibody can actually detect and, presumably, neutralize the alpha variant, the beta variant, and very likely the delta variant as well.

KWONG: So the implications of that are huge, right? I mean, it means that many people could have long-term protection against COVID no matter what variants crop up.

DOUCLEFF: Yes. And the implications of that are even bigger - right? - because it means that the human immune system is eventually going to have the advantage over this virus, that with enough exposure, even just from the vaccine, the body will eventually figure out a way to keep this critter at bay for years.

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KWONG: Michaeleen, I'm feeling my body physically relax hearing you say this. Thanks for bringing us the latest science on the nuances of our immunity when it comes to this virus.

DOUCLEFF: Thank you so much for having me, Emily.

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KWONG: Today's episode was produced by Rebecca Ramirez, edited by Gisele Grayson and fact-checked by Berly McCoy. Alex Drewenskus was the audio engineer. I'm Emily Kwong. Thanks for listening to SHORT WAVE, the daily science podcast from NPR. Come back tomorrow for more.

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