E53: The Vaccines are Coming / Kizzmekia Corbett, Sree Chaguturu, Julie Rosenberg

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This, quite frankly, is our generation’s Manhattan project.  –Sree Chaguturu

This has been a big week for vaccines. There are two vaccines under review by the FDA and the United Kingdom has become the first country to authorize Pfizer’s mRNA vaccine. In this episode, we’ll talk about the science behind mRNA vaccines, and discuss the physical and mental logistics needed to get these revolutionary vaccines to the public.

This podcast was created by Just Human Productions. We’re powered and distributed by Simplecast. We’re supported, in part, by listeners like you.

Kizzmekia Corbett: Companies have never had to try to produce an entire world worth of vaccine in such a short period of time or any medicine for that matter

Sree Chaguturu: This, quite frankly, is our generation’s Manhattan project

Celine Gounder: Hi, I’m Dr. Celine Gounder and you’re listening to EPIDEMIC, the podcast about the science, public health, and social impacts of the coronavirus pandemic. 

When Kizzmekia Corbett joined the Vaccine Research Center at the National Institutes of Health in 2014, she wanted to make her mark. 

Kizzmekia Corbett: I wanted to be different [laughs] I tend to kind of try to, like, stay, um under the radar and, and work on something that a lot of other people aren’t. 

Celine Gounder: So, in 2014, that meant studying something no one was really talking about: coronaviruses. Kizzmekia wanted to study potential vaccines for the viruses that cause SARS and MERS, short for Middle East Respiratory Syndrome. 

Kizzmekia Corbett: I mean, when I started working in 2014 at the NIH, the MERS epidemic was just dying down. We had just seen SARS about a decade before that. So I think it was pretty clear that this type of thing was bound to happen.

Celine Gounder: In 2017, she and others at NIH published research on the spike protein… the little projections sticking out of the coronavirus that give it that unique shape. 

Kizzmekia Corbett: That structure really led the way to understanding the immune landscape or what could be a good coronavirus vaccine.

Celine Gounder: Kizzmekia’s team at NIH started working with the pharmaceutical company Moderna, to help them develop the technology that could turn her research into a vaccine. 

Fast forward to 2020. That research Kizzmekia was doing on vaccines for obscure coronaviruses? It was suddenly the focus of a global effort to develop a vaccine for SARS-CoV-2. And Kizzmekia… was ready. 

Kizzmekia Corbett: And so when the, the sequence of the virus came out on January 10th, we had a plan and it was largely based on all of this research that we’d done before.

Celine Gounder: On the morning of November 16th, Kizzmekia got an email. The vaccine was 95% effective.  

To put this into context for people, how good is that for a vaccine? 

Kizzmekia Corbett: Amazing. It is Absolutely amazing. I’ve worked on, you know, these vaccines from literally from day one. Um, and I cried [laughs] because it was it actually, it absolutely shattered my all, any expectation that I could have had. 

Celine Gounder: A lot of news has been coming out these weeks about new vaccines. The Moderna vaccine Kizzmekia helped lay the groundwork for back in 2017, and helped usher through phase one trials, was submitted to the FDA for emergency use authorization on November 30th, the same week this podcast was released.

The United Kingdom became the first country to approve the Pfizer vaccine for distribution on December 2nd. 

On this episode of EPIDEMIC, we’re going to hear about the science and distribution of the two coronavirus vaccines currently under review by the FDA: the Pfizer and Moderna mRNA vaccines.

We’ll hear what makes vaccines like the one Kizzmekia worked on so special…  

Kizzmekia Corbett: mRNA technology is going to change how we think about vaccines and vaccine delivery.

Celine Gounder: What some of the hurdles will be in convincing the public to take the vaccine.

Sree Chaguturu: So these numbers, Celine, um, give me significant pause and concern about the amount of hesitancy that we’re seeing.

Celine Gounder: And some lessons we could learn when it comes to convincing people to accept the vaccine from… Elvis Presley?

Elvis: You ain’t nothing but a hound dog, cryin’ all the time 

Celine Gounder: On today’s episode of EPIDEMIC… the vaccines are coming. 

Before we talk too much about what makes Kizzmekia’s vaccine so special, let’s review what a traditional vaccine is. Generally speaking, vaccines protect people from disease by priming and preparing the immune system to fight off a virus before someone is infected. There are four kinds of traditional vaccines, but there are two you’re probably most familiar with. They’re called live-attenuated and inactivated vaccines. 

The smallpox and measles vaccines are examples of live-attenuated vaccines. These vaccines work by exposing someone to a virus that’s so weak it doesn’t make them sick… but it’s enough to teach their immune system how to fight off the real thing.

Flu shots are an example of an inactivated vaccine. These vaccines work by exposing the body to a dead virus. When the body sees these dead viruses, it recognizes them as something bad, and develops an immune response to get rid of them. 

Many of these vaccines were developed in the 1950s and 1960s.

Kizzmekia Corbett: What happened is that as technology progressed, it became clear that you didn’t need to make an immune response to the entire virus and that oftentimes it’s good enough and actually sometimes even more optimal to just make an immune response to one part of the virus. And so figuring out what part of the virus you want to make an immune response to is the first step.

Celine Gounder: So when it comes to the SARS-CoV-2 coronavirus… that means the spike protein. The same spike protein that Kizzmekia’s lab worked on back in 2017.

Kizzmekia Corbett: So if you take all the rest of the virus away and just deliver that spike protein, and cause the body to mount an immune response to that spike protein, then you can make a successful vaccine.

Celine Gounder: Kizzmekia’s team at NIH and Moderna took this idea a step further. Their vaccine uses something called messenger RNA, or mRNA for short. So, what is mRNA? In a sense, mRNA is a message… a set of instructions… a recipe for how a cell makes a specific protein. 

After a COVID mRNA vaccine is injected into someone’s arm, the messenger RNA gets picked up by cells in the muscle, and they start to make the harmless spike protein that studs the surface of the coronavirus.

When the immune system sees those spike proteins, it knows that those spikes aren’t supposed to be there. The immune system mounts a response to get rid of them. In the process, the body has learned how to identify and defeat the SARS-CoV-2 virus if it ever sees it naturally. 

Kizzmekia Corbett: So, uh, with mRNA, instead of having to make that protein outside of the body in a laboratory, we are delivering that protein to the body by a message, a messenger mRNA.

Celine Gounder: There are a lot of advantages to these mRNA vaccines. They’re fast to produce. And they create a robust immune response. Two things that really matter in a pandemic. 

But there are things we still don’t know about the mRNA vaccines under review. One question that sounds small but has big implications is if the vaccine prevents just disease…. or also infection and transmission.

Kizzmekia Corbett: So, um, sterilizing immunity is prevention of infection and um, the data that are coming out, those endpoints are prevention of disease.

Celine Gounder: This means that someone who gets an mRNA vaccine may not develop severe COVID disease… but they could still—potentially—be infected and transmit the virus to other people. We just don’t know yet.

Kizzmekia Corbett: And it’s understandably scary, right? Because such a large proportion of cases, uh, for the SARS CoV-2 are asymptomatic. And it’s notable that asymptomatic people can transmit virus onward.

Celine Gounder: But Kizzmekia says it’s important to remember that if someone has been vaccinated and they’re exposed to SARS-CoV-2 after that… their immune system will keep the virus in check…  and will block it from making too many copies of itself. So even if someone who’s been vaccinated can still be infected… we think they’ll have less virus in their body… and will therefore be less likely to spread it to others… than someone who’s never been vaccinated.

Kizzmekia Corbett: I think that sterilizing immunity is a bar that maybe people would like to see, but in all accounts with 95% efficacy against prevention of disease, people actually taking the vaccines will see these vaccines, having a really, really good effect on the downturn of the pandemic and all. 

Celine Gounder: Kizzmekia’s part in the vaccine may be coming to an end, but it’s just starting for Sree Chaguturu. 

Sree Chaguturu: My name is Sree Chaguturu, I’m chief medical officer for CVS Caremark.

Celine Gounder: Companies like CVS will be working with federal, state, and local governments to make sure the vaccine actually gets to the people who need it. We’ll hear how the vaccine will get distributed… and what can be done to convince people to take it. That’s after the break.

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On December 1st, a federal advisory committee announced its recommendations for who should get the vaccine first. The Advisory Committee on Immunization Practices said that healthcare workers and residents of long-term care facilities, like nursing homes, should get top priority. 

Sree Chaguturu: There’s nearly 60,000 long-term care facilities and skilled nursing facilities. So we will be, uh, partnering up with a little over half of them.

Celine Gounder: Staff and residents of long-term care facilities are some of the most vulnerable in the pandemic. According to the Kaiser Family Foundation, this group only makes up 6% of the COVID cases in the United States… but it accounts for 40% of the deaths. CVS has been partnering with these institutions to provide on-site flu vaccinations for a long time, so the COVID vaccine will roll out in a similar fashion there. But these mRNA vaccines require extra care. 

Sree Chaguturu: Our pharmacists come on site with all the PPE and we have our electronic health records. We administer the doses. We upload all the data on anyone who’s been actually vaccinated that day so that when we come back for the second vaccination clinic, we can make sure that people get the right second dose.

Celine Gounder: So do you have some sense as to when you’ll start vaccinating people in these facilities? 

Sree Chaguturu: So, our expectation is, uh, within days after, uh, the emergency use authorization for one or either of these leading products from Pfizer, Moderna. So, possibly as soon as, uh, the second week of December. 

Celine Gounder: And based on your experience with flu vaccination, do you have a sense for how long It’ll take to actually reach your 30,000 or so facilities that you guys are covering. 

Sree Chaguturu: I can’t see it going longer than three months or four months. 

Celine Gounder: Remember, those three months just cover CVS’s rollout of the vaccine at nursing homes and long-term care facilities.

Celine Gounder: After this first phase of vaccine distribution, other groups will become eligible. Sree says retail pharmacies will be one of the many places where people will be able to get vaccinated in 2021. But developing a vaccine… coordinating all these logistics… won’t do us any good if people won’t take the vaccine. 

Sree says CVS conducts surveys all the time to see what their customers want. Things like drive-thru COVID testing sites, for example. So, as the pharmacy chain started to plan how they would distribute vaccines, they wanted to know… what do people think about a potential coronavirus vaccine? 

CVS conducted an email survey of 5,000 participants designed to be representative of the United States. This is what they found:

Sree Chaguturu: The likelihood to be vaccinated is really a function of gender and level of education. Uh, surprisingly men were more willing than women to be, uh, vaccinated. Um, and college educated patients were more likely to be vaccinated than non-college educated, uh, patients. Um, we saw that lower-income patients are least likely to seek the vaccine right away and most likely not to get it at all. 

Celine Gounder: The survey found that African-Americans were the group least likely to want to get the vaccine. Asian and white Americans were the most likely to say they’d get it. 

Other trends were along geographic or political lines. The Midwest and West were the regions of the country where people said they were most likely to get vaccinated. The South was the least likely. Urban areas were more likely than rural. 

Politically, people who identify as Republicans or independents who lean Republican were more likely to wait to get vaccinated or refuse it all together. 

Lastly, people who use more healthcare were more likely to get vaccinated. Older people… people who are immunocompromised or have chronic health issues, like diabetes… and even people who reported previously  getting a COVID test were all more likely to say they would get vaccinated. 

Sree Chaguturu: So, really some findings here that, um, we’re unfortunately, uh, um, you know, given previous history of, uh, disparities in healthcare, we see just continuing in this data such as, uh, hesitancy by community by, um, race and ethnicity.

Celine Gounder: But the most disheartening thing for Sree was the number of respondents who said they would not get vaccinated. 

Sree Chaguturu: We have almost a, a fifth of the country that is saying that they don’t plan to receive it at all.

Sree Chaguturu: So, Celine, there’s a lot of work ahead of us to combat significant vaccine hesitancy. 

Julie Rosenberg:  Hesitancy, I think, stems from a lack of trust.

Celine Gounder: This is Julie Rosenberg. She’s the Deputy Director of Harvard’s Global Health Delivery Project. She and her colleagues are focused on how to distribute vaccines and get people vaccinated.

Julie Rosenberg: I think people have also started losing trust in, in the systems, um, in the people, in the companies, in the leadership that has been guiding the development of vaccines. Um, I think our current political environment has eroded a lot of trust.

Celine Gounder: On both sides of the aisle. The CVS survey suggests Republicans may be less likely to get the vaccine. But Democrats who saw the Trump administration’s push for a vaccine approval before the election may also have doubts about the process. To be clear, the FDA is proceeding with its normal process for vetting the safety and efficacy of coronavirus vaccines. They are not cutting corners.

But vaccine hesitancy is a problem… and one way to overcome this hesitancy is by working with trusted voices in different communities. 

Let’s go back to the 1950s. 

Polio was a serious disease in the United States. If children caught it, it could leave them paralyzed. It was not uncommon to see children with leg braces or wheelchairs. But when a vaccine was developed, not everyone was lining up to get it… especially teenagers. 

And who was a big hit with teenagers in the 1950s? Elvis Presley. 

Elvis: Kids, could I talk to you for about 30 seconds? This is Elivs Presley… 

Elvis participated in a public service campaign with the March of Dimes to encourage kids to get vaccinated.

Elvis: You know, so many kids and adults have gotten some of the roughest breaks that can happen to a person. I’m talking about polio. MOD clip

In 1956, he went on the Ed Sullivan Show and got vaccinated live on TV. 

Julie Rosenberg: And in the six months following that they saw vaccination rates increased dramatically among teenagers. So that rock and roll star was really kind of a powerful influence, um, for that age group.

Celine Gounder: Magic Johnson played a similar role in the 1990s with HIV awareness. 

Magic Johnson: I will now become a spokesman for the HIV because I want young people to realize that they can practice safe sex and sometimes you’re a little naive about it and think it’ll never happen to you. https://www.youtube.com/watch?v=VbdOQUARrEU 

Julie Rosenberg: I think it helped to break down the stigma around the disease and let people know that there wasn’t shame in talking about it. There wasn’t shame in getting tested, that it could happen to anyone.

Celine Gounder: And it doesn’t have to be celebrities. Former U.S. Surgeon-General Dr. David Satcher led an influential campaign to encourage immunization of African American children that relied on the influence of churches and faith-based organizations. Julie says another group that could play an important role is healthcare workers. 

Julie Rosenberg: They will be some of the first to get the vaccines, and people will be turning to them, whether it’s, you know, you know, a neighbor, whether it’s a patient, um, whether it’s another community leader reaching out to them as you know, experts in health, um, for healthcare workforce is often a trusted source of health information.

Celine Gounder: One of the reasons so many are hesitant to get vaccinated is the speed at which these vaccines were developed. New vaccines are rare and typically take years to develop. Kizzmekia Corbett, who helped develop the Moderna vaccine, knows this better than anyone. 

Kizzmekia Corbett: My boss is, you know, thirty years into his vaccinology career and this is the first time he’s seen a phase three all the way through. 

Kizzmekia Corbett: A lot of the stuff that we did this entire time has been groundbreaking. I mean, getting a vaccine into a phase one clinical trial in sixty-six days after a, uh, the sequence of a virus comes out is like very revolutionary.

Celine Gounder: But Kizzmekia wants people to know that everything that went into that mRNA vaccine did not happen in just those sixty-six days.

Kizzmekia Corbett: We didn’t just wake up on January 10th and say, let’s go grab this protein and let’s throw it in some new platform and see what happens. 

Celine Gounder: Years before Kizzmekia came to the NIH’s Vaccine Research Center, people were already thinking about what a coronavirus pandemic would look like…. And how to develop a vaccine for it. So when the team heard the results saying the phase three trials were 95% effective, it was a big moment. 

Kizzmekia Corbett: And we came together on our celebratory call and it, it felt like family because we’d been working together even before this. And so I want people to kind of understand how much like tenderness went into this. 

Celine Gounder: But Kizzmekia knows there is still a lot of work ahead. 

Kizzmekia Corbett: I have yet to pop a bottle of champagne and, um, I imagine that that won’t happen until we get to a place where there are significant, um, distribution of the vaccine happening and, you know, things have a downturn and that’s okay.

Celine Gounder: And things are likely going to get worse before they get better. The winter months are going to be the deadliest we’ve seen in this pandemic. So please, don’t drop your guard. Stick to your household bubble as much as you can. Wear a mask. Social distance. And if you’re going to see other people, do that outside or in really well ventilated spaces. We need to do everything possible to protect as many people as possible this winter until the vaccines can do their work… and getting everyone vaccinated is going to take time.

Kizzmekia Corbett: At this point, only a vaccine is going to substantially make this pandemic go away, and so saving lives and helping to get us back to what we can consider to be normal. That’s what we’re trying to do at the end of the day. 

EPIDEMIC is brought to you by Just Human Productions. We’re funded in part by listeners like you. We’re powered and distributed by Simplecast. 

Today’s episode was produced by Zach Dyer and me. Our music is by the Blue Dot Sessions. Our interns are Tabata Gordillo, Annabel Chen, and Bryan Chen.

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And check out our sister podcast AMERICAN DIAGNOSIS. You can find it wherever you listen to podcasts or at AMERICANDIAGNOSIS.fm. On AMERICAN DIAGNOSIS, we cover some of the biggest public health challenges affecting the nation today. In Season 1, we covered youth and mental health; in season 2, the opioid overdose crisis; and in season 3, gun violence in America.

I’m Dr. Celine Gounder. Thanks for listening to EPIDEMIC.

Guests
Julie Rosenberg Julie Rosenberg
Kizzmekia Corbett Kizzmekia Corbett
Sree Chaguturu Sree Chaguturu
Host
Dr. Celine Gounder Dr. Celine Gounder