The Science Behind The Historic Pfizer-BioNTech mRNA Vaccine : Short Wave Millions of doses of the Pfizer-BioNTech vaccine, just days ago granted emergency use authorization by the FDA, are being distributed across the country. It's the first widely-available vaccine to use something called mRNA technology. So, with the help of epidemiologist Rene Najera, Maddie explains the science behind this vaccine and how it was developed so quickly.

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The Science Behind The Historic mRNA Vaccine

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Geoff Brumfiel. What's up, Geoff?


SOFIA: Hey, now.

Hello, Pien Huang. Hiya (ph), Pien.


SOFIA: ...In a while.

EMILY KWONG, BYLINE: Hi, Maddie. I miss you so much.

SOFIA: I know. I miss your face.

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SOFIA: Yes, for the love of science itself...

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SOFIA: You're listening to SHORT WAVE from NPR.

Maddie Sofia here with Emily Kwong.

KWONG: Hi, Maddie.

SOFIA: Hey, you. So recently, we've had some sobering coronavirus news. Not only have we passed 300,000 coronavirus deaths in the U.S., but for the last two weeks, COVID-19 was the leading cause of death, ahead of heart disease and cancer.

KWONG: But that news was contrasted by something hopeful on the vaccine side of things, news that began with a simple meeting.


KATHLEEN HAYES: And I will read the votes aloud for the record. Dr. Moore voted yes.

KWONG: Following the vote of a panel of independent medical experts...


HAYES: Dr. Kurilla voted no. Dr. Rubin voted yes.

KWONG: ...On Friday, the Food and Drug Administration moved to authorize the emergency use of the Pfizer-BioNTech coronavirus vaccine.

SOFIA: It's the first COVID-19 vaccine to be authorized by the FDA. It's also the first authorized vaccine to use something called mRNA technology. And to be clear, this is not an approval by the FDA.

KWONG: Right. Emergency use authorizations are faster and have fewer steps.

SOFIA: I mean, it is an emergency, after all.

KWONG: But Pfizer-BioNTech still went through rigorous safety and efficacy trials in order to get this authorization. And the CDC also gave its endorsement the day after for use by people 16 and older in the U.S.

SOFIA: And Monday...


SOFIA: Sandra Lindsay, a critical care nurse at Long Island Jewish Medical Center, became the first person in the U.S. to receive the vaccine.


SANDRA LINDSAY: I hope this marks the beginning to the end of a very painful time in our history.


KWONG: This week, many other health care workers are following suit, taking the first of the two-dose vaccine.

SOFIA: Which is why, today, we're talking about the science behind the vaccine, how it works in your body and how it was developed so quickly. You're listening to SHORT WAVE from NPR.


KWONG: OK, Maddie. So today, we are talking about how mRNA vaccines actually work. Where should we start?

SOFIA: So in order to get more context on this vaccine, I called up Rene Najera. He's the editor of the History of Vaccines Project with the College of Physicians - Philadelphia. Rene is also an associate of epidemiology at Johns Hopkins Bloomberg School of Public Health.

KWONG: Whoa.

SOFIA: On top of that, he is a senior epidemiologist in a health department in the D.C. area.

KWONG: What?

SOFIA: Plus, he's got a little one at home.

RENE NAJERA: I've got to warn you, though, the toddler is on her way home. So they'll be here, like, in 45 minutes. And she is loud.

SOFIA: (Laughter).

KWONG: That's really, really cute.

SOFIA: Yeah. He says, you know, even though we've never had an mRNA vaccine licensed in the United States before, the basis for this technology has actually been around for a while.

NAJERA: Yeah, the '90s and the turn of the century is when the actual hardware to do this, the actual techniques in the lab become more well-understood. It's only now that you have this true global pandemic, global emergency that pushed that technology to mature rather quickly.

KWONG: And like we've talked about on the show before, this speeding along was the result of a huge effort by the global scientific community. Pretty much as soon as scientists got their hands on the genetic sequence of the virus in January, they were off to the races developing a vaccine.

SOFIA: Right.

KWONG: And like we said earlier, this is an emergency use authorization which, by its nature, happens pretty quickly.

SOFIA: Yeah. And another reason this vaccine came along quickly is because it's just simply quicker to make in the lab compared to, like, the flu vaccine or other viral vaccines.

KWONG: Yeah, those are the vaccines that I'm honestly more familiar with. So let's start there. How do they generally work?

SOFIA: So they all work by giving your body a little taste of a potential virus, just enough for your immune system to recognize, hey, there's something in my body that is not mine, react to that intruder and build up immunity to that virus.

KWONG: Right. So later, if that germ comes to town for real, your body can say, hey, I remember you; I'm ready for you now.

SOFIA: (Laughter). Yeah, exactly like that. That's how the immune system sounds. But so...

KWONG: (Laughter) Like a 1930s cartoon character.

SOFIA: Yeah, absolutely. So most vaccines use a weakened version of a virus or just little pieces of it. But that requires time to grow up a bunch of virus, to process it in order to make the vaccine. But for this vaccine, the mRNA vaccine, there's no virus in it.

KWONG: Wait, wait, wait. You're saying there's no actual virus in the vaccine at all? Because I didn't really realize that.

SOFIA: Nope.

NAJERA: And so, you know, you have this mRNA vaccine that all you need really was the genetic sequence, the template for what mRNA you were going to make. You didn't need to grow the virus. You didn't need to expose your workers at a lab to it. And so it just - you just skipped a few steps in that way. And...

KWONG: That is amazing, Maddie, to hear.

SOFIA: (Laughter) Yes.

KWONG: It's also a little confusing. Like, what does he mean, the mRNA template?

SOFIA: So mRNA vaccines take advantage of a process that already happens in our body.


SOFIA: Like, every minute of every day, our body is making this thing called mRNA, and it's like an instruction manual that tells our body how to make proteins. And so if you make a little piece of mRNA in a lab and feed it to our cells, our cells will naturally read that little piece of code, that instruction, and use it to make a protein, whatever you want. And in this case, it's a coronavirus protein.

KWONG: So it's like we're hacking ourselves.

SOFIA: Right.

KWONG: And instead of putting a bunch of proteins from the virus into the shot, we give the cells in our body the instructions to make that coronavirus protein themselves.

SOFIA: Exactly. That little protein by itself cannot give us COVID, but it is enough to trigger an immune response so that the body learns to fight it.

KWONG: Wow. So let's say I'm at a doctor's office about to get this vaccine. How do I get it? And how does my immune system actually respond to it?

SOFIA: OK. So let's walk through it. So these mRNA vaccines are an injection in the arm. After the injection, your muscle cells kind of swallow up the mRNA and bring it into the cell. Now, this mRNA doesn't get into the nucleus of the cell where your DNA hangs out. It can't. So there's no worries about the vaccine, like, messing with your DNA at all.


SOFIA: Instead, that mRNA hangs out in the cytoplasm of your cells where it gets turned into protein.

KWONG: I remember drawing the cytoplasm in bio class.


SOFIA: Honestly, I think it's an underrated part of the cell.

KWONG: Yeah.

SOFIA: OK. So after our body uses mRNA to make protein, the cell puts some of that protein on its surface, like on the outside of the cell, which allows other cells in your body to see it.

KWONG: And that's the goal, right? The point of the vaccine is for your body to recognize pieces of the coronavirus without actually having to get the coronavirus.

SOFIA: Yeah. And at this point, the vaccine kind of acts like all other vaccines. Throughout the whole process at different times, our immune system cells recognize and react to that self-made coronavirus protein. I mean, Kwong, there's a whole subset of cells where their entire job is to tattle on invaders. Like, they pick up foreign proteins that are in your body, like this coronavirus protein, and kind of, like, wave it around to other cells, like, oh, guys, I found this protein...

KWONG: (Laughter).

SOFIA: ...It's not supposed to be here. And honestly, I think it should get in trouble.

KWONG: (Laughter) I'm sure the scientific term for these is not tattle cells.

SOFIA: No, but it should be...

KWONG: (Laughter).

SOFIA: ...Because they're actually called antigen-presenting cells.

KWONG: Tattle cells is definitely memorable. I'm going to remember that.

SOFIA: (Laughter) Thank you. Thank you. So these tattle cells can activate other cells...


SOFIA: ...Including this diverse group of cells called T cells. So some of them get activated and become very murder-y (ph).


SOFIA: Those are literally called killer T cells. They go around sniffing out cells infected by the virus and kill them. Some of these T cells help raise the alarm. They bring other cells into the area. I call them supertattle T cells. You know, they're helping with the tattling.

KWONG: (Laughter).

SOFIA: And then some of those same T cells help other cells make antibodies. And so later, after you've gotten the vaccine, if you're exposed to the real coronavirus, those antibodies can recognize that protein, grab onto it and keep the virus from getting into our cells.

KWONG: And antibodies are what protect us in the long term, right? We want those.

SOFIA: That's a huge part of it. You have this initial wave of antibodies and T cells right after vaccination or infection, but your body also creates this kind of memory bank, too.

NAJERA: Once the threat is over, once there's no more percentage of the antigen, the cells will revert into kind of a dormant stage that'll - they'll still be around and still be circulating, still growing and dividing until the protein gets presented again, and then they'll activate again almost immediately.

SOFIA: And that memory is why some vaccines work for years and years after you get them.


SOFIA: Now, we don't know if this vaccine will lead to long-term immunity, but that's what everybody's hoping will happen.

KWONG: Sure. All right. Well, I have some general questions left about the vaccine.

SOFIA: OK. Let's do it.

KWONG: OK. How long does it take for the vaccine to work?

SOFIA: OK. So this vaccine is two doses three weeks apart. You see some pretty good protection around 14 days after the first dose, but way better protection after the second.

KWONG: And after the second, can I stop wearing this mask all the time?

SOFIA: No, Kwong. You keep that mask right on. Even in your closet alone right now, I want you to be wearing that. No, at this point, the vaccine has been shown to prevent people from getting symptoms of COVID-19 from, you know, those mildly annoying ones to those really scary symptoms that we worry about that can lead to death. So obviously, that alone is huge. But it's possible you could still harbor the virus in your body.

KWONG: Oh. So I could feel fine but still have the virus in my body and, I guess, pass on the virus?

SOFIA: Yeah, that's possible. And we will have more information on that at some point. But at this time, you know, it's still really important to wear masks and physically distance with people, you know, especially those who have not yet received the vaccine.

KWONG: Got it. That's really, really important to hear. OK. And there are side effects to the vaccine, yes, no?

SOFIA: Yeah.


SOFIA: Pretty much every vaccine, some people will experience minor side effects, like a low-grade fever or fatigue or achiness. And that is normal. It is actually just a result of your immune system gearing up to kind of fight. For some people who have had a history of severe allergic reactions, those people can have bad side effects.

NAJERA: That's why you get asked, you know, have you ever had an allergic reaction to a vaccine? Are you allergic to any of the components in the vaccine? And that's why you look at people and make sure that, you know, you give them the information of what to look for in case they're going to have a bad reaction so they can report back right away and get taken care of.

SOFIA: Scientists are still tracking symptoms of people from early on in clinical trials to make sure that no longer-term side effects show up.

KWONG: All right, last question - I read that one of the big downsides to these mRNA vaccines is that you have to keep them really, really cold.

SOFIA: Right.

KWONG: The Pfizer-BioNTech one has to be kept at minus 70 degrees Celsius. Why is that? And is that going to be a problem when we're thinking about how to get this to millions of people across the country, not to mention other parts of the world?

SOFIA: Yeah. So mRNA is pretty unstable, which just means it falls apart easily, especially at higher temperatures. So that's why you have to keep it really cold. So, yes, the cold storage requirements are going to put limits on distributing the vaccine. But there is another mRNA vaccine from a company called Moderna that'll be likely approved very soon. And it can be stored at a little bit of a higher temperature, like the temperature of your household freezer. Not to mention, there are other vaccines further down the pike.

KWONG: That's great to hear, especially since this is a global pandemic. We're going to need other vaccines, some that will use different technologies, some that can be stored more easily to really curb the pandemic so we can take off our masks and live our lives the way we once did.

SOFIA: Yeah. I mean, that is far off, to be honest. And it's important to keep our eye on that. But I do think it's important to celebrate this moment right now, you know? We have to keep an eye on the future and how long this is going to take to kick in. But we also have to take a moment and celebrate the sheer amount of work and investment and scientific cooperation it took to get to this moment and, you know, the relief that some of our health care workers are finally going to have.


KWONG: Maddie, thank you so much for all of this reporting. It's really fantastic.

SOFIA: Yeah. Absolutely, Kwong.

Today's episode was produced by Rebecca Ramirez, edited by Viet Le and Gisele Grayson and fact-checked by Ariela Zebede. Alex Drewenskus was our sound engineer. I'm Maddie Sofia.

KWONG: And I'm Emily Kwong.

SOFIA: Thanks for listening to SHORT WAVE from NPR.

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