Posted on by Dr. Francis Collins
More than 170 million Americans already have received COVID-19 vaccines. As this number continues to grow and expand to younger age groups, I’m filled with overwhelming gratitude for all of the researchers who worked so diligently, over the course of decades, to build the scientific foundation for these life-saving vaccines. One of them is Dr. Kizzmekia Corbett, who played a central role in the fact that, in the span of less than a year, we were able to develop safe and effective mRNA-based vaccines to protect against this devastating infectious disease.
As leader of the immunopathogenesis team at NIH’s Dale and Betty Bumpers Vaccine Research Center in Bethesda, MD, Dr. Corbett was ready, willing, and able when the COVID-19 pandemic emerged to take the critical first steps in developing what would become the Moderna and Pfizer/BioNTech mRNA vaccines. Recently, she accepted a position at Harvard University T.H. Chan School of Public Health, Boston, where she will soon open her own viral immunology lab to help inform future vaccine development for coronaviruses and other respiratory viruses.
While she was preparing for her move to Harvard, I had a chance to speak with Dr. Corbett about her COVID-19 research experience and what it was like to get immunized with the vaccine that she helped to create. Our conversation was part of an NIH Facebook Live event in which we connected virtually from our homes in Maryland. Here is a condensed version of our chat.
Collins: You’ve studied SARS, MERS, and other coronaviruses for many years. Then, in early January 2020, like all of us, you heard that something was going on that sounded worrisome in Wuhan, China. What did you think?
Corbett: Well, the story actually began for me on December 31, 2019. My boss Dr. Barney Graham sent me an email at 6 a.m. that said: “Get ready for 2020.” There had been some news of a respiratory virus outbreak in the Wuhan district of China. I honestly wrote it off as probably a strain of the flu. Then, we got back to NIH after the holidays, and it was determined around January 6 that the virus was for certain a coronavirus. That meant our team would be responding to it.
We sat down and planned to monitor the situation very closely. We knew exactly what to do, based on our past work. We would go into full force to make a vaccine—the one now known as “the Moderna vaccine” —as quickly as possible for testing in a clinical trial. The goal was to make the vaccine in 100 days. And so when the genetic sequence of this new virus came out on January 10, I sprung out of bed and so did everyone on the team. It’s been kind of a whirlwind ever since.
Collins: Tell us a little bit more about that. The sequence got posted on the internet by a Chinese scientist. So you have this sequence, and everyone gathers in NIH’s Vaccine Research Center. Then what happens?
Corbett: The cool thing about this type of technology is you don’t even need the lab to design the vaccine. All you need are the letters, or sequence, that encodes the virus’ genetic material displayed on your computer screen. We could actually do the work from our homes, obviously in close conversation with each other.
This sequence is the virus’s genetic code. Just like humans have families—brothers, sisters, cousins—viruses also have families. So, we could see when looking at the sequence of letters, how similar this particular virus was to viruses that we’ve worked with before in the coronavirus family. It was almost like “A-ha! This is the part of the sequence that represents the protein on the surface of the virus.”
We knew that we could take the sequence of that surface protein and use all of the knowledge that we had from previous years to design a vaccine. And that’s what we did. We took that sequence on our computer screen and said we said this is exactly how we want this vaccine to look. The process was as straightforward as that.
Collins: In other words, you already knew that these coronaviruses have spike proteins on their surface and that’s the thing that’s going to be really useful for making an antibody. You’d already taken this approach in developing a vaccine for MERS, right?
Corbett: Exactly, we’d done that for MERS. Vaccines are basically a way to teach your body how to see a pathogen. Over the years, as vaccinology and technology have progressed, different scientists have figured out that you don’t really need the whole virus as a part of the vaccine. You can just take a small portion of that virus to alert your body.
In this case, taking the spike protein and teaching your immune system how to specifically spot and attack it, you can now protect yourself from COVID-19. So, we used the sequence of that spike protein, with some modifications to make it much better as a vaccine. We then deliver that to you as a message—messenger RNA (mRNA) —to get your muscle cells briefly to make the spike protein. Then, your body sees that spike protein hanging out on your cells and makes a really specific immune response to it. That way the next time your body sees the spike protein, if you ever come into contact with the virus, your immune system is armed and ready to attack.
Collins: Say more about this messenger RNA approach. It’s been so revolutionary and one of the reasons that we got vaccines into people’s arms in just 11 months. Had this approach ever been used before?
Corbett: Yes, messenger RNA technologies have been in development from a basic science perspective for over 15 years. A lot of that work was funded by NIH. Soon after I got to NIH, I attended a meeting in London called Transforming Vaccinology. At the time, Moderna was a smaller company that was working to make messenger RNA technologies, mostly centered around cancer therapies. But they had started to test some flu vaccines that used messenger RNA. My question to the presenter was: “Every single time I see you guys present, it looks like mRNA technology has always worked. Can you tell me a time that it hasn’t?” And he said, “I can’t.”
So, our understanding of how this technology works to make really good vaccines predates this pandemic. I think one of the worries that many people have is how fast and how new this technology is. But all science is compounded knowledge—everything builds on itself.
Collins: Right! We only learned about messenger RNA, because back in the 1950s and 1960s, some researchers decided to figure out how the information in our genetic instruction book, our DNA, can ultimately turn into proteins. It turned out that the message that carries that information is made of RNA.
So, you knew which kinds of letters to program into the messenger RNA vaccine. Would you explain how this vaccine, its messenger RNA, produces a spike protein. Where does that step happen?
Corbett: Your cells are machines built for this kind of thing. I like to remind people that, on a day-in, day-out basis, our cells make proteins—all of the hormones and other things our bodies needs to survive. So, we’re not teaching the cells to do anything different than they would normally do. That’s important to understand.
The way that cells do this is by reading the mRNA sequence. As they’re reading that sequence, they chew it up, like eating it, and say, “Okay, this sequence is for this very specific protein.” Then, they make that protein and push it to the surface of your cells. That’s how it happens.
Collins: And for mRNA vaccines, that’s the point when your immune system says “Wait a minute! I don’t recognize that as part of me, so I’ve got to make an antibody to it.” Then you’re off to the races and develop your immunity. Now that this mRNA vaccine strategy has succeeded for COVID-19, could it be applied to other infectious diseases or even non-infectious conditions?
Corbett: Yes, I heard that about 60 new companies have sprouted up in the last year around messenger RNA technology. They have ideas for different types of infectious disease vaccines and cancer therapies. I expect that this technology will be transformative to medicine in general.
Collins: Here’s a question from social media: “Why does it take two shots for the Pfizer and the Moderna mRNA vaccines? Why isn’t one good enough?”
Corbett: The way that these vaccines work is much like an alarm clock. Imagine your immune system is in bed and the first shot is the alarm clock going off to say, “Hey, wake up and get ready.” And just like I did this morning, the immune system pressed snooze and took a little nap. But when you hear the alarm clock the second time, it’s like someone rushing into your room and pouring a cold bucket of water on you. You have no choice but to get out of bed.
That’s what the second dose of the vaccine does. It pushes your immune response to the next level. That’s why you need two shots to get the type of efficacy that you want and be fully protected for the optimal immune response.
Collins: You were a co-leader of the team that created what became the Moderna vaccine—and you ended up getting immunized with the Moderna vaccine. What did that feel like?
Corbett: It was pretty surreal. I cried. At the end of it, I felt a lot of relief after getting my vaccine, particularly after getting the second dose. There was this breath of fresh air. It was also a birthday present. I got my second dose the day before my 35th birthday, as a birthday present to myself.
Collins: I have to admit, I cried a little bit too after my second dose. It’s just the sense of relief and incredible gratitude that we’ve reached this point. Here we are with vaccines that have 95 percent effectiveness and an incredibly good safety record, which is almost better than we could have hoped for. I’m a person of faith, so there were a lot of my prayers that went into this and it sure felt like they got answered.
Corbett: Yes, same.
Collins: You are out there a lot talking to people about the vaccines. There are still about 100 million Americans that have not yet received their first dose. Many of them still unsure about getting vaccinated. What do you say to those who are on the fence?
Corbett: In this past year, I’ve spent a lot of time talking about the vaccine with people in the community. One thing that I realized, is that I don’t need to say anything unless I’m asked. I think it’s important that I listen first, instead of just speaking.
So I do that, and I try to answer people’s inquiries as specifically as possible. But people have some very broad questions. One thing that is happening is people are seeing vaccines being developed right before their eyes. That can be a little confusing. I try to explain the process, how we went from the preclinical stage all the way to the point of getting the vaccine to hundreds of millions of people. I explain how each step along the way is very highly vetted by regulatory agencies and data safety monitoring committees. I also tell them that the monitoring continues. People from the clinical trials are still being evaluated, and there’s monitoring in the real world as the vaccine is being rolled out. I think that all of those things are really important for people to know.
Collins: Another question from social media: “As a successful scientist, what advice would you give to people who are thinking about a career in science?”
Corbett: If you think you’re interested, you just have to start. There are internship programs, there are scholarship programs, there are shadowing programs all over this country and even globally that can help you get your feet wet. I think the first thing that you want to do with any career is to figure out whether or not you like it. The only way that you can do that is to just explore, explore, explore.
Collins: Didn’t you kind of roll up your sleeves and take the plunge at a young age?
Corbett: Yes, at age 16, I went off and did summer internships at the University of North Carolina. I was able to see first-hand the day-to-day life of science and what being a scientist would look like. That was really important for me. That’s what I mean by exploring.
Collins: And a follow-up question: “Is the biomedical research community welcoming to women of color?”
Corbett: Not always, frankly. I was very fortunate to have been under the wings of a lot of mentors and advocates, who have helped to advance my career to where it is now. I had great mentors at NIH. My graduate school mentor was amazing, and my main collaborator in the coronavirus field was on my dissertation committee. Even prior to this pandemic, when I was doing work that was very obscure, he checked on me very often and made sure that he had a sense of where I wanted to go and how he could help me get there, including collaborating with me.
That kind of thing is very important, particularly for women of color or anyone from a marginalized community. That’s because there will be a point where there might be a glass ceiling. Unfortunately, we don’t necessarily have the tools to break those just yet. So, someone else is going to have to break those down, and most often than not, that person is going to have to be a white man. Finding those people who are allies with you and joining in your fight for your career trajectory is very helpful.
I remember when I was choosing a college, it was a very difficult decision for me. I got accepted into Ivy League schools, and I’d gone to all of the scholarship weekends all over the country. When I was making the decision, my dad said, “Kizzy, just always go where there is love.”
That really sticks to me with every single choice that I make around my career. You want to be at a place that’s welcoming, a place that understands you, and a place that fosters the next version of who you are destined to be. You need to make sure to step back outside of the day-to-day stuff and say, “Okay, does this place love me and people like me?” It’s important to remember that’s how you thrive: when you are comfortable in and in love with your environment.
Collins: Yes, we have to move our scientific workforce into a place where it is not necessary for a white man to advocate for a talented Black woman. There’s something very wrong with that particular circumstance. As NIH Director, I want to assure you, we are motivated more than ever to change that, including through a new initiative called UNITE. We’re missing out on welcoming the talents of so many folks who currently don’t see our research agenda as theirs, and we need to change that.
Kizzmekia, this has been a lot of fun. Thank you for giving us a half-hour of your time when you’re in the midst of this crazy two-week period of moving from Bethesda to Boston. We wish you the very best for this next chapter, which I know is going to be just amazing.
Corbett: Thank you so much.
Video: COVID-19 mRNA Vaccine Q & A – Kizzmekia Corbett and Francis Collins (NIH)
Video: Lead COVID-19 scientist Kizzmekia Corbett to join Harvard Chan School faculty (Harvard University, Boston)
COVID-19 Research (NIH)
Dale and Betty Bumpers Vaccine Research Center (National Institute of Allergy and Infectious Diseases/NIH)
UNITE Initiative (NIH)
Posted on by Dr. Francis Collins
It’s truly encouraging to witness people all across our nation rolling up their sleeves to get their COVID-19 vaccines. That is our best chance to end this pandemic. But this is the third coronavirus to emerge and cause serious human illness in the last 20 years, and it’s probably not the last. So, this is also an opportunity to step up our efforts to develop vaccines to combat future strains of disease-causing coronavirus. With this in mind, I’m heartened by a new NIH-funded study showing the potential of a remarkably adaptable, nanoparticle-based approach to coronavirus vaccine development .
Both COVID-19 vaccines currently authorized for human use by the Food and Drug Administration (FDA) work by using mRNA to instruct our cells to make an essential portion of the spike protein of SARS-CoV-2, which is the novel coronavirus that causes COVID-19. As our immune system learns to recognize this protein fragment as foreign, it produces antibodies to attack SARS-CoV-2 and prevent COVID-19. What makes the new vaccine technology so powerful is that it raises the possibility of training the immune system to recognize not just one strain of coronavirus—but up to eight—with a single shot.
This approach has not yet been tested in people, but when a research team, led by Pamela Bjorkman, California Institute of Technology, Pasadena, injected this new type of vaccine into mice, it spurred the production of antibodies that react to a variety of different coronaviruses. In fact, some of the mouse antibodies proved to be reactive to related strains of coronavirus that weren’t even represented in the vaccine. These findings suggest that if presented with multiple different fragments of the spike protein’s receptor binding domain (RBD), which is what SARS-like coronaviruses use to infect human cells, the immune system may learn to recognize common features that might protect against as-yet unknown, newly emerging coronaviruses.
This new work, published in the journal Science, utilizes a technology called a mosaic nanoparticle vaccine platform . Originally developed by collaborators at the University of Oxford, United Kingdom, the nanoparticle component of the platform is a “cage” made up of 60 identical proteins. Each of those proteins has a small protein tag that functions much like a piece of Velcro®. In their SARS-CoV-2 work, Bjorkman and her colleagues, including graduate student Alex A. Cohen, engineered multiple different fragments of the spike protein so each had its own Velcro-like tag. When mixed with the nanoparticle, the spike protein fragments stuck to the cage, resulting in a vaccine nanoparticle with spikes representing four to eight distinct coronavirus strains on its surface. In this instance, the researchers chose spike protein fragments from several different strains of SARS-CoV-2, as well as from other related bat coronaviruses thought to pose a threat to humans.
The researchers then injected the vaccine nanoparticles into mice and the results were encouraging. After inoculation, the mice began producing antibodies that could neutralize many different strains of coronavirus. In fact, while more study is needed to understand the mechanisms, the antibodies responded to coronavirus strains that weren’t even represented on the mosaic nanoparticle. Importantly, this broad antibody response came without apparent loss in the antibodies’ ability to respond to any one particular coronavirus strain.
The findings raise the exciting possibility that this new vaccine technology could provide protection against many coronavirus strains with a single shot. Of course, far more study is needed to explore how well such vaccines work to protect animals against infection, and whether they will prove to be safe and effective in people. There will also be significant challenges in scaling up manufacturing. Our goal is not to replace the mRNA COVID-19 vaccines that scientists developed at such a remarkable pace over the last year, but to provide much-needed vaccine strategies and tools to respond swiftly to the emerging coronavirus strains of the future.
As we double down on efforts to combat COVID-19, we must also come to grips with the fact that SARS-CoV-2 isn’t the first—and surely won’t be the last—novel coronavirus to cause disease in humans. With continued research and development of new technologies such as this one, the hope is that we will come out of this terrible pandemic better prepared for future infectious disease threats.
 Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses. Cohen AA, Gnanapragasam PNP, Lee YE, Hoffman PR, Ou S, Kakutani LM, Keeffe JR, Barnes CO, Nussenzweig MC, Bjorkman PJ. Science. 2021 Jan 12.
COVID-19 Research (NIH)
Bjorkman Lab (California Institute of Technology, Pasadena)
NIH Support: National Institute of Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
The winter holidays are traditionally a time of gift-giving. As fatiguing as 2020 and the COVID-19 pandemic have been, science has stepped up this year to provide humankind with a pair of truly hopeful gifts: the first two COVID-19 vaccines.
Two weeks ago, the U.S. Food and Drug Administration (FDA) granted emergency use authorization (EUA) to a COVID-19 vaccine from Pfizer/BioNTech, enabling distribution to begin to certain high-risk groups just three days later. More recently, the FDA granted an EUA to a COVID-19 vaccine from the biotechnology company Moderna, Cambridge, MA. This messenger RNA (mRNA) vaccine, which is part of a new approach to vaccination, was co-developed by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The EUA is based on data showing the vaccine is safe and 94.5 percent effective at protecting people from infection with SARS-CoV-2, the coronavirus that causes COVID-19.
Those data on the Moderna vaccine come from a clinical trial of 30,000 individuals, who generously participated to help others. We can’t thank those trial participants enough for this gift. The distribution of millions of Moderna vaccine doses is expected to begin this week.
It’s hard to put into words just how remarkable these accomplishments are in the history of science. A vaccine development process that used to take many years, often decades, has been condensed to about 11 months. Just last January, researchers started out with a previously unknown virus and we now have not just one, but two, vaccines that will be administered to millions of Americans before year’s end. And the accomplishments don’t end there—several other types of COVID-19 vaccines are also on the way.
It’s important to recognize that this couldn’t have happened without the efforts of many scientists working tirelessly behind the scenes for many years prior to the pandemic. Among those who deserve tremendous credit are Kizzmekia Corbett, Barney Graham, John Mascola, and other members of the amazing team at the Dale and Betty Bumpers Vaccine Research Center at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
When word of SARS-CoV-2 emerged, Corbett, Graham, and other NIAID researchers had already been studying other coronaviruses for years, including those responsible for earlier outbreaks of respiratory disease. So, when word came that this was a new coronavirus outbreak, they were ready to take action. It helped that they had paid special attention to the spike proteins on the surface of coronaviruses, which have turned out to be the main focus the COVID-19 vaccines now under development.
The two vaccines currently authorized for administration in the United States work in a unique way. Their centerpiece is a small, non-infectious snippet of mRNA. Our cells constantly produce thousands of mRNAs, which provide the instructions needed to make proteins. When someone receives an mRNA vaccine for COVID-19, it tells the person’s own cells to make the SARS-CoV-2 spike protein. The person’s immune system then recognizes the viral spike protein as foreign and produces antibodies to eliminate it.
This vaccine-spurred encounter trains the human immune system to remember the spike protein. So, if an actual SARS-CoV-2 virus tries to infect a vaccinated person weeks or months later, his or her immune system will be ready to fend it off. To produce the most vigorous and durable immunity against the virus, people will need to get two shots of mRNA vaccine, which are spaced several weeks to a month apart, depending on the vaccine.
Some have raised concerns on social media that mRNA vaccines might alter the DNA genome of someone being vaccinated. But that’s not possible, since this mRNA doesn’t enter the nucleus of the cell where DNA is located. Instead, the vaccine mRNAs stay in the outer part of the cell (the cytoplasm). What’s more, after being transcribed into protein just one time, the mRNA quickly degrades. Others have expressed concerns about whether the vaccine could cause COVID-19. That is not a risk because there’s no whole virus involved, just the coding instructions for the non-infectious spike protein.
An important advantage of mRNA is that it’s easy for researchers to synthesize once they know the nucleic acid sequence of a target viral protein. So, the gift of mRNA vaccines is one that will surely keep on giving. This new technology can now be used to speed the development of future vaccines. After the emergence of the disease-causing SARS, MERS, and now SARS-CoV-2 viruses, it would not be surprising if there are other coronavirus health threats in our future. Corbett and her colleagues are hoping to design a universal vaccine that can battle all of them. In addition, mRNA vaccines may prove effective for fighting future pandemics caused by other infectious agents and for preventing many other conditions, such as cancer and HIV.
Though vaccines are unquestionably our best hope for getting past the COVID-19 pandemic, public surveys indicate that some people are uneasy about accepting this disease-preventing gift. Some have even indicated they will refuse to take the vaccine. Healthy skepticism is a good thing, but decisions like this ought to be based on weighing the evidence of benefit versus risk. The results of the Pfizer and Moderna trials, all released for complete public scrutiny, indicate the potential benefits are high and the risks, low. Despite the impressive speed at which the new COVID-19 vaccines were developed, they have undergone and continue to undergo a rigorous process to generate all the data needed by the FDA to determine their long-term safety and effectiveness.
Unfortunately, the gift of COVID-19 vaccines comes too late for the more than 313,000 Americans who have died from complications of COVID-19, and many others who’ve had their lives disrupted and may have to contend with long-term health consequences related to COVID-19. The vaccines did arrive in record time, but all of us wish they could somehow have arrived even sooner to avert such widespread suffering and heartbreak.
It will be many months before all Americans who are willing to get a vaccine can be immunized. We need 75-80 percent of Americans to receive vaccines in order to attain the so-called “herd immunity” needed to drive SARS-CoV-2 away and allow us all to get back to a semblance of normal life.
Meanwhile, we all have a responsibility to do everything possible to block the ongoing transmission of this dangerous virus. Each of us needs to follow the three W’s: Wear a mask, Watch your distance, Wash your hands often.
When your chance for immunization comes, please roll up your sleeve and accept the potentially life-saving gift of a COVID-19 vaccine. In fact, I just got my first shot of the Moderna vaccine today along with NIAID Director Anthony Fauci, HHS Secretary Alex Azar, and some front-line healthcare workers at the NIH Clinical Center. Accepting this gift is our best chance to put this pandemic behind us, as we look forward to a better new year.
Coronavirus (COVID-19) (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
Dale and Betty Bumpers Vaccine Research Center (National Institute of Allergy and Infectious Diseases/NIH)
Moderna (Cambridge, MA)
Pfizer (New York, NY)
BioNTech (Mainz, Germany)