S1E53 / The Vaccines are Coming / Kizzmekia Corbett, Sree Chaguturu, Julie Rosenberg

Companies have never had to try to produce an entire world worth of vaccine in such a short period of time.

This, quite frankly, is our generation's Manhattan Project.

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.

I wanted to be different. I tend to kind of try to like stay under the radar and work on something that a lot of other people aren't.

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

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

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

That structure really led the way to understanding the immune landscape for what could be a good coronavirus vaccine.

Kozmicki'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 Kozmicki 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.

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.

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?

Amazing. It is absolutely amazing. I've worked on, you know, these vaccines from literally from day one, and I cried because it was— it actually, it absolutely shattered any expectation that I could have had.

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 1 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.

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

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

These numbers, Celine, give me significant pause and concern about this, the amount of hesitancy that we're seeing.

And some lessons we could learn when it comes to convincing people to accept the vaccine from Elvis Presley? On today's episode of Epidemic, the vaccines are coming. Before we talk too much about what makes Kuzmichya'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 4 kinds of traditional vaccines, but there are 2 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 '60s.

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.

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.

So if you take all of 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.

Kizmicki'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 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.

So with mRNA, instead of having to make that protein outside of of the body in a laboratory. We are delivering that protein to the body by a message, a messenger mRNA.

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.

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

This means that someone who gets an mRNA vaccine may not develop severe COVID disease, but they could still be infected and transmit the virus to other people. We just don't know yet.

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

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.

I think that sterilizing immunity is a bar that maybe people you 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.

Kasmikiya's part in the vaccine may be coming to an end, but it's just starting for Sri Srinivasa Gutturu.

My name is Shree Chagatiru. I'm the chief medical officer for CVS Caremark.

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. 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.

There's nearly 60,000 long-term care facilities and skilled nursing facilities, so we will be partnering up with a little over half of them.

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 similar fashion there. But these mRNA vaccines require extra care.

Our pharmacists come on site with all the PPE. You know, we have our electronic health records, we administer the doses, we upload all of 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.

So do you have some sense as to when you'll start vaccinating people in these facilities?

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

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?

I can't see it really going longer than 3 to 4 months.

Remember, those 3 months just cover CVS's rollout of the vaccine at nursing homes and long-term care facilities. After this first phase of vaccine distribution, other groups will become eligible. Shree 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. Shree says CVS conducts surveys all the time to see what their customers want. Things like drive-through 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.

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

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 Republican or independents who lean Republican were more likely to wait to get vaccinated or refuse it altogether. 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.

Some findings here that, given previous history of disparities in healthcare, we see just continuing in this data, such as hesitancy by community, by race and ethnicity.

But the most disheartening thing for Sri was the number of respondents who said they would not get vaccinated.

We have almost a fifth of the country that is saying that they don't plan to receive it at all. So, Celine, there's a lot of work ahead of us to combat significant vaccine hesitancy.

Hesitancy, I think, stems from a lack of trust.

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.

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

On both sides of the aisle, the CBS 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.

Today, the tragedy of paralytic polio can be prevented in individuals protected by all 3 recommended doses of polio vaccine. However, there are still millions of Americans who have received only one or two of the doses, or none at all. These are today's potential victims.

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?

Hey kids, could I talk to you for about 30 seconds?

Elvis Presley.

This is Elvis Presley. If you believe polio is beaten, I ask you to listen.

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

You know, so many kids and adults too have gotten just about one of the roughest breaks that can happen to a person. I'm talking about polio. Sure, we're on the way to conquering it thanks to the Salk vaccine. But take it from me, it sure isn't a lick yet.

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

And in the 6 months following that, they saw vaccination rates increase dramatically among teenagers. So the rock and roll star was really kind of a powerful influence for that age group.

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

I would now become a spokesman for the HIV virus because I want people and young people to realize that they can practice safe sex.

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.

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.

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

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.

My boss is 30 years into his vaccinology career, and this is the first time he's seen a Phase 3 all the way through. A lot of the stuff that we did has been groundbreaking. I mean, getting a vaccine into a Phase 1 clinical trial in 66 days after the sequence of a virus comes out is, like, very revolutionary.

But Kizzmekia wants people to know that everything that went into that mRNA vaccine did not just happen in those 66 days.

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.

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 3 trials were 95% effective,— it was a big moment.

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

But Kazmikia knows there's still a lot of work ahead.

I have yet to pop a bottle of champagne. I imagine that that won't happen until we get to a place where there is significant distribution of the vaccine happening and, you know, things have a downturn. And that's okay.

And things are likely 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.

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.

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