Dr. Kizzmekia Corbett — The Novel Coronavirus Vaccine

Thursday, May 21, 2020

Perhaps now more than ever, it is undeniable how integral vaccines have become to public health. Vaccines protect us from a whole host of infectious diseases, including chickenpox, measles and the seasonal flu. With a new threat at hand, scientists at the NIH swiftly developed a vaccine candidate against the novel coronavirus that causes COVID-19. The pre-clinical effort was driven in part by Dr. Kizzmekia Corbett. 

Dr. Corbett is a viral immunologist and research fellow in the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID). Learn more about the work taking place at the VRC at https://www.niaid.nih.gov/about/vrc

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>> First off, I just want to thank you for all the round-the-clock work that you and your team have been doing. I know everyone is super grateful for you and all the other scientists and healthcare workers at the NIH and around the world trying to get us through this as quickly and safely as possible. And on a personal note, I just want to say it is a pleasure, because I worked in a vaccine development lab myself a couple of years back, so it's cool to, you know, be able to go back to that a little bit.

>> Yeah, sure. Um, it's always a pleasure actually to be kind of featured at the NIH. So I'm extremely grateful and happy about the opportunity.

>> Great. Well happy to have you. So I guess it goes without saying, but personally, if you had told me where we'd be, where we are right now, I don't think I would have believed you. And as the number of COVID cases ticks upwards, it's easy to see the stress that it's putting on hospitals. Um, and not that you can compare, but how has the outbreak changed your day to day in the lab?

>> I mean apples and oranges comparing what my day was like, you know, essentially before Christmas and then coming back to what was knowledge that the outbreak in Wuhan District in China was a coronavirus, which was the virus that I had been working on for the past five years, or the virus family. Um, so before, you know, in early December what was happening is my little small three or four person team, we were doing assays, really looking at specific details about the immune response that we would hypothetically like to elicit from a vaccine perspective. And I was actually pipetting still, not that much, but you know, at least a couple of days a week I was able to get into the lab.

>> Are you still in the lab though? Or are you teleworking mostly?

>> I have been going to the lab because I actually liked the lab. You know, I haven't been really doing any experiments, but I go to the lab for like peace of mind. So I generally am in the lab from about 4:00 AM until about 8:00 AM before anyone else gets there because we're obviously working on a socially distant protocol just like everybody else is.

>> Right.

>> So, you know, what my team under Dr. Graham direction is doing now is directing the preclinical portfolio behind mRNA-1273 which is the product that we're developing with Moderna. So the development process, um, for this vaccine is slated to break some world record, I presume. Part of that is because we got a really good head start. We have been working with Moderna, not in the context of this coronavirus obviously, but in the context of MERS coronavirus, which was the latest before this coronavirus, being transmitted among humans and having some level of pandemic potential. So we studied that vaccine responses for MERS coronavirus, um, delivered by Moderna's mRNA platform.

>> Ok.

>> And that kind of helped us to build up, you know, some significant level of confidence around the platform with our antigen. So, um, you know, we kind of knew what kinds of immune responses we'd be targeting. I mean, even the small things that I think a lot of other people will have to figure out by starting from scratch with their novel vaccine program. I mean, we even knew that our antigen would probably 99% at least express by mRNA because we already done this before. So, um, you know, we were able to cut that kind of first stage of preclinical development and characterization of the product down to what you know is 66 days.

>> Speaking of the preclinical stage and the antigen that you're talking about, what approach did you take to design this like best test dummy for the immune system to train on all these years before? So like in other words, how do you determine the target that will stop the virus from spreading either for corona specifically or in more general terms?

>> Yeah, so, um, viruses have surface proteins that solely function to help the virus to bind to a human cell. So that initial step, the attachment of the viral protein to a human cell is what is the first step at facilitating infection. And so, um, from a vaccine development standpoint, if you can stop that initial step in some form, then you can essentially stop infection and then that means you can stop transmission. Um, and you know, on a community level that means you in so many ways cured, um, the community of the virus. And so that's kind of the aim of the vaccine

>> And the protein is this so-called spike protein, right, that everyone's kind of been hearing about on the news?

>> Right. So in this case, the protein is called a spike protein.

>> And this allows the virus to latch onto the cells and kind of infiltrate to like take over the machinery and replicate.

>> Yes, the process is called fusion. So it basically means like melting the cell membrane and the virus membrane together, so that they in so many ways become one and the genetic material or the RNA from the virus can get inside the cell and start to replicate. We essentially want to stop that process. And so what we're doing with this vaccine is we've, you know, over the past few years, designed spike constructs, so, um, ways to express the spike protein to deliver them to people or in our case pre-clinically to animals that will give them, um, the best immune response.

>> Right. And just to clarify, cause when I used to work in a vaccine lab, we would make the actual protein like purify and then introduce it as the antigen. But you guys are using mRNA to deliver the genetic information. Right? And then that way the body's own cells express the virus and kind of alert the immune system that this guy doesn't belong here.

>> Yeah. So we've done it both ways.

>> Oh okay.

>> Um, but in this particular case, we are doing it via mRNA for several reasons. Um, one of which is in the middle of a pandemic it's quicker, right? Instead of having to make grams and grams and grams of clinical grade protein to be delivered to people, you can basically just use the person's body as the protein factory.

>> That makes sense. Smart, very smart.

>> And deliver, um, the mRNA to them in a method that Moderna has become somewhat of a famous company off of, right. So their proprietary platform, um, is tried and true. It's been tested in people before. They know how to do it, and well. It was somewhat of a, I would say seamless connection.

>> And it's so impressive, like you said before, that you've been able to get this to clinical trials in record time. From what I've read, it took something like 20 months to get a vaccine ready for human trials after the outbreak of SARS in 2003, and then it was something like six months for Zika, um, when it came around the corner in like 2015. And you guys have cut that time in half. So are there any lessons from those previous outbreaks that you've applied and consequently, you know, expedited everything?

>> I personally didn't work on those outbreaks, but my boss did. Both of those records were his record. But the truth of the matter is, what is happening here is just about the level of organization and forethought that was put into a plan before the pandemic

>> Mhmm.

>> So you know, if we have to like see the sequence and then call Moderna and get agreements going and talk about the strategy--even if we have to like, in so much detail as to say, well, what doses do we even want to test in mice first? All of that, all of those details and nitty gritty things were worked out three years ago, um, in the context of MERS.

>> Wow.

>> The other thing about the 66 days is that everyone is excited about it except us. Had we tested the MERS vaccine all the way through phase one already, we would probably be initiating a Phase 2 as we speak.

>> I see. So you would have, not skipped this first, you know, the first phase, but it would have been a little bit faster just because you would have done it with the MERS vaccine.

>> Right. Because you would have been able to see similar characteristics of your vaccine in the first few patients. You would have been able to say, "Oh it's safe. Go to the next step." Cause you already in a, in a cohort of people proven that the platform was safe for use, you know, however many years ago. And I think that's really the lesson. So you know, I've gotten the question: "Well how do you feel like you could shorten it more? Or since you're not really necessarily..." I mean, to be fair, I am, I'm content with it and I'm happy that we're able to do it quickly. But I just know that there are places that could use improvement. And one of those is really about going at risk with some of these platforms into people before the pandemics occur. And having a phase one data profile that suggests that the platform is safe.

>> Right. So do you think that will change in the future? Just like preparation, maybe not just for like coronaviruses, but pushing these vaccine development projects faster as opposed to waiting for a pandemic to hit.

>> Yeah, I think this does open the eyes of, you know, what I like to say, the people with the pocketbooks, because to be fair, these are multimillion dollar studies. I mean, even the preclinical side of things takes millions of dollars when you add it all together. And that's with production of the material...

>> Right. Right. I mean, I heard it takes like close to a billion dollars for a vaccine to go from like inception in the lab to dissemination in the world. So like that's not surprising at all.

>> Absolutely not surprising.

>> But how did, uh, Moderna, like get involved with all of this? How did you strike up that partnership?

>> So, Moderna's claim to fame, to be fair, is really cancer treatment. And thinking about what mRNA does, it seems like, why wouldn't you try it? And then when they did, the data were just so beautiful. Most of which was around influenza vaccine. You know, they've expanded it to Zika and [inaudible], you know, CMV and all of these other things. But it was almost, every time at least that I saw the data and obviously I was seeing data that was um, you know, the numbers were crunched and it was on a shiny screen at some conference somewhere. But every time I saw the data it just looked like, does this ever fail?

>> Yeah.

>> And we, um, struck the Moderna because it became clear that one of the gaps that was missing from a pandemic preparedness perspective was the speed portion. So what we could do at the VRC is design antigens in collaboration with other people. Like for example, ours is designed in collaboration with, uh, Jason McLellan's group at UT Austin. And then we are essentially experts at that and we're experts at viral immunology to the point of testing vaccines and understanding immune responses that are going to be productive. We even have a clinic and we even have a vaccine production plant, but we're not really necessarily set up on any scalable level to make genetic material.

>> Right, right, right. Well, I guess now that it's kind of shown these promising results in mice and it's in phase one clinical trials, what are you looking for in the next stage? Like how do you know if it will be a success?

>> So, a measure of success in the first phase of trial is whether or not it's safe and whether or not we see an immune response.

>> But safety is the priority at this point.

>> Safety is absolutely the priority across all of the points. But the way that phase ones are designed is that they are really designed to only assess, on a statistical level, safety. Um, will we be able to say, you know, yes, 44 out of 45 people got a whopping immune response. Absolutely. We'll be able to tell that, but it won't, that's not necessarily the main endpoint of the study. And so our measure here is just, do we elicit an immune response to some level and is the product safe in humans?

>> Gotcha.

>> And if the answer to both of those is yes, then we will move forward. Um, it's just about whether or not we can produce the data that the FDA wants to see to insure that going to the next phase from a regulation standpoint makes sense.

>> Right. And you're still involved in the whole process, right? Like you're working through it all the way until the end.

>> So, um, our lab, um, well not my particular team because we have robots that do this. Like once it gets to humans, it's like the VRC has robots. We no longer have to pipette clinical samples and that's just by way of being blessed to be in a center with those types of resources. But we are, the VRC is analyzing the samples from the phase one clinical trials. The VRC is doing the preclinical stuff for the phase one clinical trial or to put forward the agenda towards phase two and the VRC will stay involved in understanding the immune response, probably through all of the phases of the clinical trial.

>> Got it.

>> We probably will be more so concerned about research questions after this point because we're still scientists and we're still trying to make our next round of vaccines if necessary better. So we want to answer some real nitty gritty research questions, you know, and those are the types of things that we'll do after phase one.

>> I see. Well now perhaps the question that you get the most, but the one that I think I'd be remiss if I didn't ask, um, when can we expect a vaccine to be available?

>> Um, so the goal of everyone, um, is to be in general population and what will be 18 months from sequence. So the sequence came out in January. So maybe 12 months, but thus far we are at least on track, so we're happy about that.

>> Yeah, that's great news. Um, and there is some worry I guess that, you know, the corona will mutate and evolve into like several strains kind of like flu. Um, in that sense, will the vaccine, do you think, will it be like an annual flu shot and then it changes every year? Is that a possibility?

>> No, that's not a possibility. The last time I checked sequences for coronaviruses that were isolated from around the world, there were no indications that there was any level of sequence variability to be concerned about, especially in the spike protein. So the amount of sequence variability was about one tenth of what you would find in one HIV patient. So this virus is mutating very slowly. And so any vaccine that started with the first strain, which is the strain that we started with for our vaccine, should be protective for years. If the vaccine elicits the right type of immunity, the protection will not wane based on sequence variability. Part of the reason for this is something that we already know about coronaviruses. Number one is, unlike flu in that there's not a segmented genome. So pieces of the genome don't just, in nature, swap out with each other. And so by the time you get back to like September of the next year, the virus has shuffled all the way around the world and you have a completely different virus.

>> Right, ok.

>> That doesn't happen in this case. And the second thing is that coronaviruses have an innate ability to proofread. So you know when you write a paper, before you submit your paper to your teacher, go back and read over it to make sure you didn't make any mistakes. Coronaviruses do that for their genome. Um, it's hard even for us to force coronavirus to mutate in a lab dish.

>> Really?

>> Yeah. I mean there are methods that you can add, um, selective pressure. So basically applying pressure to the virus in a dish and then seeing whether or not the viruses that it produces are different than the parent viruses. And that takes some level of intricate study to do as opposed to, you know, if we were to do that with like influenza, what we'd get out would be, you know, in two passages it'd be completely different. Or HIV for example, you could just look at it and mutates. So, you know, it's even hard for us to do it in lab. So, you know, in nature, obviously there's going to be some level of difficulty.

>> Right. Um, well how did you come to the NIH and how did you become kind of the lead on developing this vaccine?

>> I applied to a program at the NIH called the Undergraduate Scholarship Program. I was awarded that scholarship and so I was allowed to come to the NIH every summer and do research. And I fell in love with the NIH because of just the vast amount of different things that are happening on campus, not just science. I mean I like go to concerts on our campus and like I walk through the clinic specifically because I know that there's an art gallery that changes every month. So the NIH was from my perspective at that time, the place to be when it came to science.

>> Right. So it was no question that you wanted to come back, you know, build a career here.

>> There were absolutely no questions, especially because of the type of research that I wanted to do, which I'm doing is translational. And so being at a place that had the bench, um, which I supervise, you know, scientific lead, and then the bedside, which a clinic we have, um, as well. So I, I felt it was just a really good fit for me and the way that I became scientific lead of the coronavirus is partially because I wanted to have a research niche under the VRC's very brilliant product portfolio that was different then a lot of other people at the VRC studied because I didn't want to have to compete. That's partially it. And also, you know, having studied coronaviruses at least at that time, which the VRC wasn't necessarily planning to take into the clinic, gave me some level of intellectual freedom that I prefer. You know, I was able to ask some scientific questions that were important for knowledge and understanding of vaccine responses, but not necessarily with the purpose of moving a vaccine into clinical trials. What that shows though is that now all of those things matter, right. And so, um, it was really around for my academic agenda under the VRC's umbrella. All of it kind of just fit together into a nice seamless package.

>> And thank goodness it did. I mean look at you now, you're like a national hero for a lot of us.

>> Yeah. Thank goodness that it did--not for me actually. Um, but for, I've thought about it and I wonder what if we didn't have an antigen to deploy during this time? Um, and so I think about that. I think about without the collaboration with Moderna, we would not be able to even start to even think about addressing next season and nobody in the world would be able to. So, it's not about me. I'm grateful for the ability to respond in this way, obviously, but I'm really, really, really, really grateful that the knowledge just kind of presents itself.

>> Yeah. I think we're all very grateful.

>> Yeah. At this point it's very clear that it's for the world.

>> Yeah. That's a scary thought to think about. You know, what, what could have happened if you guys hadn't been on the ball before this all happened. So knock on wood. [knocking]

>> My mom has this saying, she's like, well you can't miss what you never knew. So, you know, at the end of the day we would all just be scrambling the same way we do for every other virus. You know right now we probably would be getting like protein for like animal experiments or something...I don't know what we would be doing. But it would all come together in the end for good, I think.

>> Yes.

>> But it just would not be this quick.

>> I think so. Um, I'm kind of interested to know, I think thanks to the quarantine people are finding like a new sense of appreciation for the big things like you know, obviously your health, but also the smaller like, you know, grocery shopping or even just going to a restaurant on like a Friday night. So how has this experience changed your outlook? Both as a scientist and as a person?

>> I'm from North Carolina and I just by way of being the only child of seven that's, you know, not in North Carolina, I was always having to go home for something; a birthday party, I don't know, someone having a baby, like whatever. And so I used to get somewhat annoyed by that cause it was just like expected of me. And I'm like, well, you know, I have a life in Maryland, but now I just want to see my family.

>> I know, same.

>> That's the thing that I missed probably the most. Um, I think I took for granted some of the restaurants in my area that I didn't realize that I ate at so much that closed down.

>> Which ones are those? Not to plug them, but just out of curiosity.

>> Well, so I, I live in a, um, you know, like a very diverse neighborhood. So like Ethiopian food...

>> Ah yes.

>> Salvadorian food...

>> So good.

>> All these places that aren't open right now [inaudible]. Oh man, I should've eaten Ethiopian just one last time. And from a work perspective, you know what-- my boss will probably listen to this and be very happy that I said it out loud-- I kind of was like in cruise control, um, maybe taking a little bit of things for granted because there were certain things from a publication standpoint that I didn't necessarily have to worry about getting scooped on. And so it kinda like was like, "Oh, I'll write the paper one day." The level of discipline that I have around those things, um, now has completely changed. And I think a lot of that is also just ignited by just the drive to get data out. I mean, I also, I'm finding that I actually like being home and by myself. I'm not really-- you know, my mom sends me care packages with candles and trail mix. I'm like eating that and lighting my candles.

>> What else could you need? Yeah, totally.

>> Yeah. It's cool.

>> All right, great. Well is there anything that maybe I didn't bring up that you think is pertinent or worth talking about?

>> I'm trying to say this on all of my interviews. Um, I really want people to understand that there is a method to the madness and there is a reason for the season, so to speak. You know, this virus is said to have upwards of a 40% community attack rate. So what that means is that at the end of this all, 40% of us could have been exposed. And that's a pretty large number...

>> Yeah.

>> ...for a season of a virus. Stay at home because that's the only way that you can ensure protection for yourself and for your family. And you know, there is going to be light at the end of the tunnel, but the tunnel is longer, the longer we decide to disobey laws and rules. So let's just all just try to for a second, just step outside of ourselves. I think this is a moment for that in general. Some of the things that we're going to have to do are not about us. They're about other people.

>> Right.

>> Part of us staying at home is around protecting our community from widespread transmission. And so let's just all just try very hard...

>> Right. Um, well thank you so much for your time. This was very informative.

>> Yeah, sure. I'm very happy to do this and you gave me a very exciting lunch break today. So thank you.

>> Good, I'm glad. Well, thanks so much Dr. Corbett.

>> Yeah sure. Take care.


>> As of mid May, Moderna has received approval from the FDA to move mRNA-1273 to phase two. The NIH is working with Moderna to expand clinical trials in 2020.