Video and Text Passages
Part of the Putting COVID-19 Vaccines to the Test Curriculum Collection.
Part 1: How Do You Prepare for a Pandemic of a Virus That Doesn’t Exist Yet?
Years before SARS-CoV-2 even existed, scientists who study viral pathogens knew that a pandemic caused by a novel coronavirus was likely.
In December 2019, health experts became aware of a fast-spreading virus in Wuhan, China.
At the end of 2019, I published two reports that looked specifically at whether countries, governments, the world was ready for a pandemic and unfortunately found that while we've gotten a bit better, there were still many gaps that remained.
It's important that you understand the virus that you're dealing with. And this is the hardest part when responding rapidly to a pandemic threat. And even once you understand what the virus is, you may not understand very much about the virus if it's new.
There's an old adage that when America catches a cold, Black America catches pneumonia. Whenever there's a crisis and it could be an environmental crisis or a health crisis, the people who are most vulnerable already are the ones that are most likely to be hard hit.
The COVID-19 pandemic is not likely to be the last global pandemic we experience. So it's very important that we all learn more about how pandemics happen, how better public health measures can lessen their impact, and why vaccines are a vital tool for fighting infectious disease in general.
Sometimes people when they hear the word pandemic think that it means simply a very serious or deadly disease. And that's not necessarily the case. Pandemics can occur even with pathogens that cause mild diseases. But, really, what makes something a pandemic is its geographic spread. And usually it involves many parts of the world.
It only took a few weeks from when scientists first learned of the pathogen that causes COVID-19 to when the World Health Organization issued their highest level of warning for it on January 30, 2020.
COVID-19 is the disease caused by the coronavirus that we call SARS-CoV-2. The virus typically infects the cells in the respiratory tract, and it damages the cells. And that can make it difficult for people to take in oxygen. And so that's why it's quite a serious disease and why some people can get quite sick, and, ultimately, some people can die.
The simplest definition of a virus is something with a genome that relies on its host cell for its propagation, for its replication. Many viruses don't cause any symptoms at all. Coronaviruses are everywhere in our environment.
And most of the time, they cause a few symptoms and sometimes the common cold. Like a lot of viruses that are transmitted in aerosol, we inhale them. And it turns out that coronaviruses are particularly happy in our nasal passage in general. It's only when the genome of the coronavirus changes and causes it to infect different tissues or causes it to be more infective that we start to worry about it.
Respiratory pathogens are difficult pathogens to control. And they have a number of characteristics that make it easy for them to spread and go on to cause global pandemics. When you get sick with a respiratory pathogen, the illness and the symptoms that you may have at first look like many other illnesses that you may have, a common cold or even allergies.
Respiratory pathogens also tend to have something called a short incubation time, which is the period from when you've exposed to when you go on to develop symptoms or become contagious. Pathogens with short incubation periods are hard to control because if I'm sick and if I give it to you and you become sick in say two days, and then you can give it to somebody else who could become sick in two days, there's a very narrow window to act to try to stop transmission from one person to another. Respiratory pathogens are also difficult to stop in part because they just spread really easily between people.
I wasn't surprised at all that COVID-19 had a disproportionate effect on communities of color. There's a huge amount of studies that show that people who belong to racial and ethnic minority groups in this country and also people who have lower levels of income are more likely to become ill at younger ages. I think it's important for us to know that health disparities are caused by exposures to things in our environment and to the way we distribute our resources within our society.
So there's no reason to believe that COVID-19 would affect people of different racial or ethnic groups differently based on anything about their biology. Many of these people are also overrepresented in essential worker groups. And so they were the people who had to be out there when everyone else could be safe at home.
Well, essential and frontline workers have certainly been at greater risk for coronavirus infection. The data shows us that everyone is susceptible to this virus. And that's because of where the virus comes from. It's not unusual for the viral infections that make us sick from season to season to come from an animal host or what's called an animal reservoir. We call that zoonotic movement.
Sometimes a virus will jump that our immune systems have never experienced. We call these viruses novel. They shock our immune systems and our immune systems just can't really deal with them.
We've actually had experiences with new coronaviruses that have jumped from animals to humans in the past. So the first situation was in 2003. That was called SARS. That went on to cause an epidemic that sickened about 8,000 people in the world.
And then, later, we had something called MERS, which was Middle East Respiratory Syndrome. So scientists have been working on developing coronavirus vaccines since pretty much that first epidemic in 2003.
We're always developing new technology. That's the beauty of science. Early in the pandemic, a lot of focus was put on both the classical ways of developing vaccines and on mRNA vaccine development.
So from the beginning, the mindset was we're going to develop a vaccine. But in order to begin using the vaccine on the general population, we had to test to make sure it was safe and it kept people from getting seriously ill. And we had to do this as quickly as possible.
Part 2: How Do You Develop a Vaccine for a Novel Disease in Less Than a Year?
How thousands of volunteers are recruited and how the clinical trials are conducted.
There's two major parts to vaccine development. One is developing the chemistry and the delivery of the vaccine, and the other is getting it tested and getting it through clinical trials. Scientists were able to get through both of those processes remarkably quickly and safely for the COVID-19 mRNA vaccines.
A clinical trial is a study where a certain number of people receive the vaccine, and a certain number of people don't get it. We compare what we call the experimental group to a placebo or control group.
The racial distribution in clinical trials and in vaccine trials is supposed to represent, as much as possible, the population for whom the vaccine is intended. I think there's been more recognition among scientists that it's really important to have people from really diverse environments and backgrounds involved in the trials.
The messenger RNA vaccines give your body very specific instructions to make a very specific part of the virus so that it can train your immune system to go after the virus as soon as it sees it. The vaccines themselves do not contain the virus at all. The messenger RNA that your body's cells take up do not in any way interact with your cell's own genetic material.
The muscle cells use the mirror. They make the spike protein. Your immune system goes after it, and then, after a few weeks, it's gone-- gone from your body entirely. No more spike protein, no more vaccine-- gone. What's left behind, though, is the knowledge of what that spike protein looks like. And your immune system uses that knowledge to respond if it ever sees the virus trying to enter your body.
mRNA vaccines are very rapidly developed, and it's because they're very simple. They are based on a gene in the genome of the infectious virus so we can easily synthesize the messenger RNA that's targeted toward that virus.
Any virus has 10 to 20 proteins that it expresses. But usually only one or two of those invoke a protective immune response. So when you design a vaccine, you only need to plan to show the immune system one or two of those proteins. But you need to know which those are.
They are often the proteins on the outer surface of the virus. In the case of coronavirus, it's the spike protein, and that's the piece that sticks up and gives it its name "corona," like crown.
These spike proteins are what it uses to attach to surfaces of cells in our bodies, and so these spike proteins are very specifically structured. Past research has shown the importance of the spike protein to coronavirus vaccines.
We also had done research on SARS-CoV-1. There was a group of research teams that worked on that virus, including here at the Vaccine Research Center, and we studied a prototype vaccine for that virus, encoding that spike protein.
And then later, researchers at the NIH were studying MERS, which was caused by another coronavirus. They were able to show that its spike protein was the key to making a prototype vaccine against that coronavirus as well.
So now fast forward to December of 2019. There was a lot of interest and concern about what was happening with this outbreak in China. We didn't yet know it was a coronavirus, but a lot of coronavirus experts thought it was likely to be. It just had those characteristics.
So they decided to pivot, and on about January 15, decided, let's do this. Let's make a prototype vaccine for SARS-CoV-2.
It was apparent to scientists around the world that we had to act quickly. And because so much of the vaccine research and development had already been done with other coronaviruses to identify the spike protein, the scientists were able to synthesize the mRNA for the SARS-CoV-1 vaccine and begin clinical trials in March 2020. That's a much faster time frame than for vaccines that have to be researched from scratch.
What we didn't know when we were planning these trials in spring of 2020 was where the outbreak would be most present at the time that the efficacy trials were being done-- summer and fall of 2020. We used what's called predictive analytics to try to assess what's happening in the outbreak now, which communities are becoming infected. We looked for trial sites with experience who had been involved in these kinds of efforts before. We brought them all together and said, we need all of you to participate.
Generally, for efficacy trials for vaccines, we use a double-blind strategy to eliminate bias. So the research teams-- the doctors, the nurses who are conducting the trial, giving the shots, assessing safety-- and the participants who are enrolled and receiving the shots-- neither of them know who got what.
One aspect of blinding a trial is that you can ensure that the participants in the trial all behave the same way. They don't know if they got a vaccine or not. So they all have to be careful to avoid infection.
In the case of SARS-CoV-2, it was easy to-- very rapidly and in large, large numbers-- see how the vaccine was working. It was sort of like trial by fire, really. The fact that the virus was widespread around the country was an advantage to vaccine developers and to the vaccine testing because it meant large numbers of people could participate in the trial. Basic statistics tells you the threshold of infections that you need to meet. Once you see that threshold, it's very easy to analyze how well the vaccine protects people.
Part 3: How Do We Know the Vaccine Is Safe and Effective?
The safety and efficacy results of the COVID-19 vaccine trials.
When we came to the COVID situation, it was very clear to us that communities who were hit the hardest were often communities of color. So we wanted to make sure that the trials that looked at safety and efficacy of the vaccines had a large enough number of people from different backgrounds that we could see clear signals in all of the populations that would be important for the vaccine to be delivered to later.
I think it's really important that the COVID-19 vaccine has been tested in people of a wide range of ages, demographic groups, things like by race and ethnicity in both men and women, as well as in people who have certain chronic diseases like heart disease and diabetes. One of the reasons that's really important is because we want to make sure that the vaccine is safe in people regardless of what age they are or what gender they are. But we also want people to be able to see themselves among the people who have been tested because that also makes people feel like I could imagine myself getting that vaccine.
In the case of the Moderna vaccine efficacy trial, the results came out to show that the vaccine had a 94.1% vaccine efficacy. To help put that in context, if a vaccine does nothing, the percent reduction of disease would be a vaccine efficacy of 0. If a vaccine completely prevents infection and no one in the vaccine group gets infected, only the placebo group, that would be a vaccine efficacy of 100%.
So 94.1% is very high. Most vaccines that we know, like flu vaccines and others, don't reach that level of vaccine efficacy when they're tested. So this was a very high vaccine efficacy. We were very excited about this data.
The way we arrive at the number that determines how efficacious any kind of treatment is, including a vaccine, us we look at among the people who got the vaccine, how many of them actually ended up getting infected compared to among the people who didn't get the vaccine or were in the control group, how many of those people actually ended up getting the infection? But we also like to look at not only does the vaccine protect people from getting infected, but does it actually also protect them from getting sick enough that they require treatment or hospitalization or that they end up dying?
When the COVID vaccine was developed, the one by Moderna, in particular, I was invited to become part of the data safety monitoring board for those trials. So I was able to participate in looking at how those studies were recruiting and enrolling people from different racial and ethnic backgrounds, different age groups, and to look at the monitoring of the safety and the effectiveness of that vaccine. The fact that these people were followed for up to three months, up to six months and we didn't see safety issues come up in those groups means that the vaccine is safe.
When they saw, for example, that the Moderna vaccine was effective in about November of 2020, they said to the study team leadership, we have a signal that would indicate efficacy. And we don't see a safety concern. So you need to start the process of authorization or approval.
When you're conducting a study like the Moderna vaccine clinical trial, you're looking for what's called a signal in the data, a statistical signal. And this is what tips researchers off that they're on to something. The signal says that the experiment has gone on long enough and produced enough data so the scientists can be confident in the results. It was obvious very quickly that the signal was going to be very, very strong and that the vaccines developed by the different pharmaceutical companies were very efficacious.
Often once we start using a vaccine, we also study people who receive the vaccine not as an official part of a clinical trial, but just they got it from their doctor, they got it from somewhere. And we still compare people who receive the vaccine versus people who didn't. And that's when you hear the term vaccine effectiveness.
We know that COVID-19 vaccines are effective because once we began to administer the vaccine to certain groups of people, we noticed that their death rates, hospitalization rates, and their infection rates went down dramatically. So, for example, we started out with people over age 65, those who were very vulnerable to getting COVID-19 and dying from it. And we saw their death rates go down dramatically.
It's really important that people continue to get vaccinated. Some people can't get the vaccine because they have allergies or other health conditions that make it questionable for them. So it's not only for you that you get vaccinated. You get vaccinated to protect yourself from getting sick, but it also helps other people around you who are vulnerable not get sick. So it's really kind of like a community responsibility, something we all do to help each other.
Part 4: What Is the Future of Pandemics and Vaccines?
How vaccine technology and public health measures can prepare us for the next pandemic.
Our society was not prepared for this pandemic. We tended to focus a lot on how to treat people once they got sick, but we had much less preparation for preventing the spread of the infection and for educating people and motivating them to do things to protect themselves from getting sick.
I think the overarching lesson from all of this is that it's really important to have very strong public health systems, laboratories, the ability to diagnose and test people to know what's causing their illness and to know who's well and who's sick.
There are some communities where there's a high level of mistrust in health care, public health, and in science. Those communities tend to be communities of color, and their mistrust is well-founded because there have been generations of discrimination and just really egregious treatment of people in those communities by scientists and by health professionals and frankly by our entire society, lots of other institutions.
What I try to say to people in those communities now is that science and health care continue to change. Scientists are required to involve people from diverse communities in their science. It's no longer acceptable to not tell people what the risks are of being involved in certain studies, and so there are lots of laws and regulations that have now been introduced that weren't there before.
Also scientists are slowly becoming more diverse, so we have lots of scientists who are from communities of color, many of whom were actually involved in developing the COVID-19 vaccine, in serving on the data safety monitoring boards as well as just studying the public health effects of COVID-19.
Vaccines paved the pathway back to normalcy and help end our concerns about pandemics. They're incredibly important tools for giving people long-term protection against pathogens.
I would predict that most of our vaccine development in the future is going to be through mRNA technology. It's quicker. It's more flexible. The synthesis of mRNA is one of the simplest biochemical processes that we know of. You can synthesize mRNA for multiple parts of the virus that you want to target. Or if you get a new strain that's resistant to a previous vaccine, you simply have to change the mRNA little bit to make a new vaccine that's effective.
Viruses are always changing, and so when we develop vaccines that are designed to work against a certain variant, we want to give them right away. Because what will happen is if a lot of people don't take advantage of that vaccine, the variants will start to develop and circulate, and pretty soon the virus will change to the point that the existing vaccines don't work anymore.
It's not that the science is bad. It's that these viruses can be so tough that they sometimes outstrip the speed with which we can understand them. And this is the nature of modern human viral infection and vaccine development and treatment development. It's very complex, not so complex that science can't understand it.
One thing we can do is we can survey populations of organisms where we think the virus might be coming from and get an idea of how the virus changes in those natural populations. People have known for a long time that understanding the wild populations, their reservoirs, for these infectious agents is very important. And that's where natural history comes in. That's what makes the work that people do at the American Museum of Natural History really important.
Another thing we need to understand is that the impact that humans have on natural populations of organisms influences how easy it is for something like a coronavirus to jump from an animal population into a human population. And a lot of the things that we do as humans that are destructive of the environment are bringing those populations closer to human populations and making the opportunities for jumping much more probable.
If it sounds to you like there are always these new viruses that are emerging and potentially posing threats to people, that's because there are. So we are increasingly seeing important outbreaks happening in parts of the world that we have to study and understand and stop so they don't go on to become epidemics or pandemics.
One of the beauties of science is that we learn things about the natural world using science, and then we can take what we've learned and make predictions about the natural world that are oftentimes very useful to human health.
That said, there's still a lot of challenges that we have, and some that I have seen that really worry me are vaccine hesitancy and the level of myths and disinformation that spreads about viruses and vaccines. There is a lot of that, and I think one of our big challenges going forward is to make sure that enough people understand scientific concepts so that they can critically examine the information they see and judge fairly and accurately and with facts whether they should get vaccinated or how worried they should be about pathogens.
I'm optimistic that things will change because I've seen throughout this pandemic period that people are now becoming more aware of how interconnected we are. We really need to work on some long-standing issues that have been around for a long time. So there are things like access to safe housing to water to food to a job that pays a living wage and to health care. So we really have to work on those basic what we call social determinants of health and making sure that everyone has access to those things. That way people will be as healthy as they can possibly be and they'll be in the best position to protect themselves when there's a crisis like a pandemic.