COVID-19: vaccines and therapeutics

[0:00:07]

RICK WEISS: And welcome, everyone, to this media briefing from SciLine on vaccines and antibody-based therapeutics. I want to take just one minute to introduce folks to SciLine. For those of you who may not be familiar with us, we are a fully philanthropically funded, editorially independent free service for reporters based at the American Association for the Advancement of Science in Washington. Our sole mission is to help get more research-based evidence into reporters’ news stories. We do that through a variety of services that I encourage you to check out at sciline.org. And among those services are media briefings like this one, on the record, for you to use.

Today, we have two preeminent researchers in the field of vaccine development and antibody-based therapeutics. We’ll hear first from Dr. John Mascola, who is the director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in the National Institutes of Health in Bethesda. John has a deep expertise in infectious diseases and immunology and has been involved in vaccine research programs for HIV, for influenza, Ebola, malaria, Zika. Vaccines exist for some of those diseases now and they don’t for others, so he knows something about what a challenge it is to make a safe and effective vaccine for human use. And he’ll walk us through some of the different approaches to making effective vaccines, and he’ll give us a progress report on COVID-related efforts.

Our second speaker will be Dr. Amy Jenkins, program manager within the Biological Technologies Office at DARPA, the Defense Advanced Research Projects Agency. Her work has focused on the role of antibodies in the fight against infectious disease threats. And she will fill us in on how scientists are working to identify the most promising antibodies for the fight against COVID-19 and on work to produce antibodies or recruit naturally occurring antibodies to prevent disease and perhaps even to treat it, as is being attempted, for example, through the use of convalescent serum. So fuller bios are on our website, but I’d like to get right to the meat of the matter. So let me start with you, Dr. Mascola. I’ll turn it over to you.

[0:02:31]

JOHN MASCOLA: OK. Well, thank you very much, Rick. And good afternoon, everybody. I’m going to take a few minutes to go through a couple of slides, which I’ll share here with you – just a second. OK. So, again, thank you. And what I’ll do is, in just a few minutes – five minutes or less, actually – walk you through a little bit of an overview of where we are with vaccine development. So first of all, I’m going to start with just a little bit of science because I think the background is key for understanding the way the vaccine field and the antibody field are thinking about this. So on the left of your screen, you can see a nice transmission electron micrograph of the SARS virus. And the reason that the coronavirus name comes from is the fact that there’s a crown or a light surrounding the virus as it tries to enter a cell. And that is, in fact, the surface protein that people sometimes refer to as the spike protein. And so immediately to the right, you can see an atomic-level model of that spike protein. That derives from scientists studying the protein either by crystallography or what we call cryo-electron microscopy.

So we actually know exactly what that protein looks like. We know how the virus uses it to enter a cell. And we know, and as you’ll hear about, how antibodies can attack that protein and block the virus from entering. So, importantly, vaccines teach the immune system to make antibodies that can block the virus from infecting cells. And, also, vaccines activate other immune responses to fight viral infection. So that’s some basic background on the virus. And here’s a little bit of background on how we think about vaccines. Some of you likely know this. But if we take, for example, a protein vaccine that you can see up at the top, that’s a common way that we vaccinate. One makes the subunit or a part of the virus completely safe and innocuous so that it is not – doesn’t contain any live viral parts. That protein can be injected into muscle, teach the immune system to recognize that form of protein.

The immune system makes antibodies and other responses, and that helps protect a person. Some newer concepts for vaccinology include the use of DNA or RNA vaccines. And I show in a little schematic below at the bottom of the slide there that when we use RNA, as an example, it’s just genetic material. But that genetic material includes the gene for the same spike protein. So what that means is the RNA can be injected into muscle. The muscle cells take up the genetic material. Those muscle cells then produce the protein that the gene tells it to produce. In this case, it would be the same spike protein. So rather than deliver the protein itself, the body makes the protein. But the result is the same. The immune system makes antibodies, and those antibodies can block the virus. So this is a slide showing you some examples of current vaccine products. It’s not an all-inclusive list, but it does include some of what we call the major vaccine platforms. And we talk about vaccine platforms to discriminate the different types of vaccines.

So one type of vaccine is the protein subunit I was just talking about. And there are examples of vaccines that we all know – hepatitis B or influenza – where those vaccines are protein subunits. And below that are the genetic vaccines I was mentioning, which can be either in the form of DNA or RNA. And then there are viral vector vaccines, which are usually very harmless, maybe a cold-type virus, which is called an adenovirus. And the genes of the coronavirus are put in there, and the same thing happens. We can inject that into the muscle, and it teaches the body to make proteins of interest. On the right are some of the vaccine companies that are using these various platform technologies. So at the top, you see Novavax and Sanofi making protein subunits and Inovio, Moderna and Pfizer working on genetic vaccines, AstraZeneca, Janssen and Merck working on viral vector vaccines. And, again, there are many others, but these are some of the vaccines and the vaccine candidates that are advancing into clinical trials. So I wanted to just briefly make the point of what the timelines are in a broad sense and make the point that there’s been very rapid scientific progress.

So first of all, just terminology – I think you’ve heard that the virus is called SARS-CoV-2 to indicate the fact that it’s related to the original SARS virus that was isolated in 2002. And the disease that the virus causes is called coronavirus disease or COVID-19. So in – as this epidemic proceeded, the genetic sequence of the virus was first made available from Chinese investigators on January 10, 2020. And that allowed for very rapid development of vaccines, including genetic or mRNA vaccine approaches that I just mentioned. That happened because the genetic sequence that we get from the virus – without having the virus in hand, the genetic sequence can be used to construct genetic vaccines. And those types of vaccines can progress quickly to the clinic. So what does that mean? For example, a vaccine phase one clinical trial started in mid-March 2020. Literally about two months from the time the virus was first identified, there was the first vaccine in a phase one safety trial. That’s very rapid timelines for vaccinology. And then, importantly, various types of vaccines are in clinical trials, some of which I mentioned. DNA, RNA, protein subunits, viral vectors and inactivated virus vaccines have all been developed by various groups, sometimes combinations of academic and biotechnology and pharma groups, to bring these vaccines into clinical trials.

And then, importantly, everybody’s interested in when vaccines will be available. In order for them to be available, we have to test that the vaccine works. That’s called a phase three trial. So a phase three trial will test if a vaccine works or it’s efficacious. The earliest phase three trials will begin over this summer. And it is possible that initial effectiveness information could be available by the end of 2020. So that is where you often hear the timeline – when might vaccines be available? It could become available once we know when they work, and we think we can get answers about whether they work by the end of the year. And then, finally, just some broad strokes on the vaccine development process. So as I mentioned, phase three trials of several types of vaccines are in progress or will be in progress. And then in parallel, there is a very strong effort – governmental effort in this country and in various places in the world to scale up and manufacture vaccines so there is no gap between the information above, which is the information about whether the vaccine works, and availability of a vaccine.

So that’s different than a standard approach. Usually, we would make a vaccine, test it, wait to see if it works. If it works, then we would begin to manufacture it for distribution. Here, things are going to happen in parallel so that, assuming a vaccine works, it becomes available very rapidly after that. In the United States, the FDA would review clinical data and decide if a vaccine should be licensed for use. They have the regulatory authority. And there are analogous regulatory authorities for most countries. And our Centers for Disease Control would make recommendations of who should get a vaccine. So the goal would be to provide the right type of phase three information. And the hope is that that information is encouraging and that allows for the licensure of vaccine early in the new year. I’ll be happy to stop there, Rick, and turn it back over to you.

[0:10:13]

RICK WEISS: Great. A fantastic overview of how things work and where we stand and a great setup for more details if people want to get into that in the Q&A, as I’m sure they will. But why don’t we move ahead to Dr. Jenkins?

[0:10:32]

AMY JENKINS: Thank you very much, Rick. And thank you, John, for that introduction. I’m going to try, attempt to share my screen here. It’s asking me for some preferences. Uh-oh. Let’s see. I probably should’ve tried this out. I appear to be having some technical difficulties here.

RICK WEISS: No problem. Take your time.

JOHN MASCOLA: Rick, I see a question. Should I answer that while we’re waiting?

RICK WEISS: Let’s hold off on the Q&A till the end, and I will present them through chat mode. Thanks.

JOHN MASCOLA: OK.

RICK WEISS: Yeah, we might be able to display your slides for you.

AMY JENKINS: Yeah, we may have to try that. Apologies. I don’t know – this is a brand-new computer, literally just a couple days ago. And so that may be part of the issue here. Oh.

RICK WEISS: There we go.

AMY JENKINS: Great. Fantastic.

RICK WEISS: Just give a signal when you want the shot – slides to change.

[0:11:57]

AMY JENKINS: Thank you. Apologies, everybody, for that technical glitch. So, again, thanks, Rick and John, for – Rick for the introduction and John for kicking us off here. As the name DARPA indicates, we are part of the Department of Defense. And as part of the Department of Defense, we often spend a lot of time thinking about what we can do to do things the most rapid manner possible. For example, we may be deploying military personnel with very little notice. And we would want to provide them with the type of what we call medical countermeasures, so those are vaccines or therapeutics or things to diagnose disease. We want to be able to send them off with all of those things in place very quickly. Being that we don’t necessarily know what we’re going to encounter, we like to have technologies in place to allow us to very quickly identify things if something new emerges, as what has happened here with this novel coronavirus.

So on the next slide is just a little – interesting little graphic overview of what we tried to do here. So like I said, we’re very interested in how we can do things very quickly. And we are also very interested in using these molecules called antibodies. So antibodies are actually naturally produced. You saw on John’s slides our body naturally produces them when we’re exposed to either a vaccine or when we’re exposed to a pathogen. So if you get sick, your body makes antibodies against that pathogen to try to fight it off. If you get a vaccine, your body also makes antibodies against that subunit or portion of that virus or that pathogen to help you have preventive measures in the future. And so while we really like antibodies – we think these are great molecules. They’re natural to the human body. The human body naturally produces them. We also really like them because they can be used in two manners. They can be used to prevent somebody from getting sick. They can also be used to treat somebody that is sick. So we have dual use, if you will, on these molecules. And so we wanted to invest in this technology. And we began looking at this type of technology about five or six years ago and how could we really make this a very robust technology that we could use in a very rapid setting.

Now, you notice I say the word rapid there. About five years ago, maybe 10, the state of the art was really that while antibodies may work, they were incredibly slow. It could take us several years to find the best antibody from a patient that had recovered from a disease. Additionally, once we did finally find that antibody after several years of work, it could, again, take us several years to manufacture it, to make lots of it, to produce it. And, obviously, when you add that up, that is a years timeline. And that is not a timeline that we could really use in deployment cases or that we could use in civilian populations. If we had an outbreak, as we were thinking many years ago when we started this, if there was an outbreak, we don’t have years to wait. And so we wanted to invest in these technologies to very quickly find antibodies and to manufacture those antibodies. So when I say find, what do I mean? So what I mean there is we actually take the blood that people that have recovered from an infectious disease or from a pathogen – we take their blood that they donate. And we actually go on a fishing expedition and try to identify the best antibodies in there.

There will be a lot of antibodies in there. And many of you are likely hearing about a technology such as convalescent plasma – we’re hearing about that a lot in the news right now – being used against COVID. So this is the – you take the plasma from somebody that has already recovered from COVID. The plasma is basically the blood minus all the cells. So take out the white cells and take out the red cells, and it just leaves behind the proteins or those antibodies and some other things that that person made to recover. And you actually give that to another person to help them recover. That’s great. It’s not particularly scalable. So you may get – for every person that wants to donate their plasma, you may only be able to treat a handful of people with that plasma. What we want to do is go into that plasma or that blood, find the best antibodies – ’cause not all of them are great – find the ones that are really the good ones and then manufacture them in large bioreactors off somewhere else and give them back to hundreds of thousands, if not millions, of people.

Again, we could use those to either treat those patients that are critically ill, or we can actually give them to people that are healthy and hopefully prevent disease. So you may be wondering, why would we want to prevent disease? Isn’t that what a vaccine does? Well, it absolutely is what a vaccine does. But many of you, as you are likely very familiar with, you get your vaccine. Oftentimes, you may have to come back a couple weeks later and get another booster shot. Additionally – you hear this many times with your flu shot – you may get the shot, and then it takes a couple weeks for your body to really produce that protective response. So we have a little bit of a gap there. Even from the time somebody is administered a vaccine shot, they may not be fully protected against that pathogen for several weeks, maybe even months. And what we can do with an antibody is we can give it to them immediately, and it is immediately protective. Basically, as soon as it’s injected into the body, it is protecting this patient from disease or immediately treating that patient.

Now, the difference is that the vaccine is meant to be long-term. Hopefully, that immunity will last for a fairly long time, oftentimes years, sometimes a lifetime. These antibodies will not last forever. They will last for maybe a couple months. And then they’re going to go away. So we really do see these as complementary technologies, where you can use these antibodies to provide immediate immunity or to treat critically ill patients. That’s going to go away after some time. And then you could use a vaccine to impart long-term immunity. The one additional thing I’ll note here is that we typically do not envision antibody technology being used for the whole, entire population. Vaccines are more appropriate in that space because antibodies are quite difficult to manufacture. Oftentimes, they require an IV, so that is a little bit more difficult to administer. But they absolutely could be used in those personnel that are at high risk, so potentially in nursing homes for COVID-19. You could think about, potentially, front-line health care workers or even the close personal contacts of somebody that did get sick. So those are some situations in which we think we could use antibodies to prevent disease. And, obviously, I don’t think I need to explain how we would use antibodies in those critically ill patients in the hospital.

One minor point that I want to point out here on the next slide is how we manufacture antibodies. So as it stands today, we obtain that sample from those patients. We screen those cells, and we find those antibodies. And we can do that very quickly now. The technologies that DARPA has invested in, a process that used to take many months to potentially years we can now do in approximately two to three weeks. And we have done that for this coronavirus outbreak. We have identified antibodies approximately three weeks after the first blood samples were received. Then we have to manufacture them. We have to make a lot of them. And there’s really two ways we can do that. And as you can see in these purple arrows here, we split that into two directions. On the bottom of the side, the first way we can make them is what we call protein antibodies. This is kind of the more traditional way to make these. They’re made in large, giant stainless steel bioreactors. And they’re infused into a patient either in an IV or, occasionally, they can be given through just a standard injection into your muscle. This process traditionally took a very long time. It could take up to years.

There have been advances in the past half a decade or so that have allowed this process to be a little faster. It is an established process, I will say, that process on the bottom of the slide. It is not something that DARPA has invested heavily in, but it is a process that has been used repeatedly for many different products that are currently on the market. Oftentimes, many of the commercials you see at night on TV are for exactly these types of molecules, these antibodies. So companies know how to make these, and they’re fairly well-understood. So because of that, we decided for this outbreak to actually move towards using those protein antibodies on the bottom of the slide. We grow them up in large bioreactors and try to move as fast as possible. Now, where I said, again, that’s not a particularly fast timeline, it has been shrunk quite a bit. And we have demonstrated and have now been able to – from the time we obtain a sample from a patient till the time that the first sick patient was dosed with these antibodies that came out of that large reactor on the bottom of the slide was about 90 days.

So the first patients have received some of these antibodies, and that occurred back in very late May. So we’re very encouraged that that timeline was approximately 90 days, but we want to go even faster. That’s the role of DARPA. We really want to move fast. And we would like to trim that down to maybe even less than 60 days. So if we want to do that, we’re going to try to do something similar to what John explained for those RNA or DNA vaccines. So up on the top, rather than make those antibodies as a protein, we can actually deliver the blueprint, so we can make the RNA or the DNA. Those are a little easier to manufacture. It’s a little faster. And so we may actually, ultimately, in the future be able to trim this timeline so that it doesn’t take us 90 days, but it could be less than 60. I will say that we are anticipating deploying this technology against this current pandemic, but we don’t believe it’ll have as big of an impact as those antibodies and those technologies that are a bit more established.

So on the next slide, I’ll just very quickly talk about what that DNA or RNA looks like. And, actually, thanks to John, I don’t need to really spell this out too much because, as you can see over here on the far right-hand side of the slide, John already explained that, that you can actually do this for a vaccine. Well, we’re doing the same thing but for an antibody. So rather than injecting the antibody directly into the person, we inject its blueprint or its RNA or DNA into the person, and we let their own cells produce that antibody for them. Again, we think that this could be immediately protective. It could potentially be used in therapy, although that has not yet been proven. And this is, again, a very – fairly new approach to antibodies. Again, we do not see this as a replacement for vaccines. We see it as the potential complement to vaccines. We believe that it could provide immunity almost immediately – if not immediately, within three days of the time that it’s injected into the body.

So these are kind of the – kind of novel approaches that DARPA is taking. And so just my final point will be just to reiterate that we are approaching this from this very novel RNA and DNA vector, this blueprint approach, but we are also currently deploying that traditional protein approach in really record pace from what has been done in the past in under 90 days. So with that, I will turn it back over. And thank you again for sharing the slides.

RICK WEISS: I’m glad that worked. Good to have backup. And thank you both for those very clear introductory explanations. So now, reporters on the line, you can put your questions into the Q&A icon at the bottom of your screen there, and we will start working through some of those. If you do want to address your question to one or the other of our speakers, go ahead, although I’m going to encourage both of them to chime in as appropriate on these things. And I’m going to start right now with a question that came in even before we quite started. Leave it to the investigative reporters to get a jump on things.

[0:23:40]

RICK WEISS: This is a question via NICAR from Eddie Burkhalter from the Alabama Political Reporter. Can you discuss the possibility that we may not get a good, safe vaccine by early 2021? Should the public temper hopes for a quick vaccine? I’ll start with you, John.

[0:24:37]

JOHN MASCOLA: So scientists are always reticent to promise, but I think there’s enthusiasm in the field based on a number of things. One, anytime we have a disease for which there is natural immunity – that is, after someone gets infected, the body makes immune response, and that person is then generally protected – then we have a sense that we can reproduce that with a vaccine. So an example where that doesn’t happen so well is HIV or tuberculosis. An example where that does happen well is all the diseases we know – childhood diseases like measles, mumps, where you get infected once and you’re protected. Coronaviruses infect people – other coronaviruses.

Generally speaking, people become relatively immune. That means you may get infected with a cold virus, a coronavirus, but you don’t get severely ill. And we know from those data, and we know from some animal model data with SARS and MERS that vaccines can protect. So there’s a lot of enthusiasm that eventually we’ll get there. I think the tougher part of the question is, will we get there this year? And the answer to that is we will know by this year if the vaccines work. I can’t promise one way or the other. But if we’re a bit fortunate and they work, then early 2021 is not an unrealistic goal.

RICK WEISS: Amy, did you want to add anything to that?

AMY JENKINS: I think that’s exactly – yeah, I have nothing to add there. Thank you.

[0:25:58]

RICK WEISS: OK, great. Question here from Andrew Joseph at STAT News for Dr. Mascola. Do scientists need to determine what the correlates of protection are for the virus in order to develop vaccines? If not, what is the importance of determining the correlates of protection? Maybe you should define that for all of us.

JOHN MASCOLA: Sure. We use the term correlates of protection all the time. And it means just what the words say, but what it means is that we understand what parts of the immune system correlate with actually being protected. For example, is it an antibody that binds to the virus or neutralizes the virus or some kind of a killer CD8 cell? And so we do try to define that for every specific disease. You don’t formally need to know that. So one can go make the vaccine somewhat empirically, which means make it and test it. And in the old days, that’s how all the vaccines were made – made a measles vaccine and a mumps vaccine and tested it, and if it worked, it worked. And then after that, we’d go back and figure out why it worked. In modern vaccinology, we like to do both at the same time. And so I’d say the answer to the question is a bit of a mix.

We do understand some correlates of immunity to coronaviruses. We’re trying to quickly understand if they are the same for this SARS-CoV-2 and then take advantage of them for the vaccine design. And I think that’s the current process. Most of the vaccines that I told you about are taking advantage of the fact that we think we know what kind of antibody response to generate, and that’s what the designs are based on.

[0:27:29]

RICK WEISS: Great. Here’s a question from Rosemary Westwood at WWNO Public Radio in New Orleans. I think this is for you, Amy. Can you explain a little more about how well antibodies might be working to protect people and how long they last? We’re hearing a lot about antibody testing, but it’s not clear to me how useful it is.

AMY JENKINS: Yeah, absolutely. So I think that there’s two different things, there’s two different components of that question. The first is that your natural antibody response, so those people who were infected and then got sick and recovered, and how long are they going to be protected? And I think, as John mentioned, you know, we don’t know the entire answers. We think there’s probably some level of protection there. Those people may get reinfected, but it may be much more moderate or not as severe. And we don’t necessarily know how long their immunity will last. So we don’t know how long their natural antibodies will last necessarily right now. The approach we’re taking with the antibodies that we are developing – so we typically take patients that have recovered from this pathogen in the past month or so, so we know that they still have an antibody response.

We find those antibodies and, as I mentioned, we grow them up. We then can do things to those antibodies to ensure that when we give them back to other people after we make them that they actually will last for approximately three months. So typically, the – what we call the half-life, so the amount of time it circulates in your blood, is around 150 days. That’s what we’re hoping for with some of these technologies. Again, we won’t know until we test that. But the hope is that if we can properly develop those that we will actually be able to provide a protective concentration of antibodies inside your blood in that shot that will provide protection for approximately three months.

[0:29:21]

RICK WEISS: Great. Here’s a question from Catherine Roberts at Consumer Reports. Why is the DNA/mRNA approach preferable to traditional protein vaccines?

JOHN MASCOLA: So, sure, I can answer that, at least to start. The – mRNA and DNA are not necessarily preferable. They’re faster. So we call those types of vaccine approaches synthetic vaccinology. We can synthesize the vaccine in the lab ’cause it’s just genetic material. So one can respond to a pandemic very quickly, and that’s why the RNA vaccines were first into phase one. They also are potentially a very good way to induce both antibody and cellular responses. So there’s a lot of enthusiasm about the approach. But it’s tempered by the fact that there aren’t licensed vaccines yet for DNA and RNA, so they haven’t really been made and scaled up and commercialized yet. So the traditional approaches, like making a protein, while they take a little longer to get to the clinic, we know we can scale them up. So the current thinking is we should do both of those in parallel because we don’t know what works. And if they both work, then we’re better off.

[0:30:37]

RICK WEISS: A question here from Sean Hamill at the Pittsburgh Post-Gazette. Amy, I’ll toss this your way. What is the best possible timeline for antibody therapy being approved for use in people?

AMY JENKINS: So we have now begun testing in humans, and that was in 90 days in patients. So I think that that is record – that is record pace. I don’t think that is; I know that is record pace. The hope for approval – we have to see if it works. So we want to ensure that it actually helps these patients get better. We also want to show that it’s safe. So we will be undergoing those clinical studies. We will complete these kind of early phase one studies. We will hopefully move into what we call phase two studies, where we look for the efficacy and the signal that says these patients are actually getting better statistically. We’ll move into that phase likely in the summertime. My hope is that we would have the opportunity potentially to – it would be on a similar time frame as the vaccines in that we may have approved or actually products that could be used under what we may call compassionate use, if you will, for patients that need this potentially life-saving drug sometime in the fall. I think the likelihood of complete licensure of a completely, fully licensed product, we’re probably looking more in the 2021 time frame for that.

RICK WEISS: John, I’m sure you’re in discussions with FDA over there at NIH. Does that estimate comport with your sense from FDA?

[0:32:12]

JOHN MASCOLA: Sure, absolutely. And, you know, just to comment that at the beginning, everyone’s a bit conservative. We want to make sure that for these products, whether it’s a vaccine product or an antibody product, although we’ve used vaccines that are similar, antibodies that are similar, each of them is a new product, you know? So we call the studies first-in-human. So one always has to start off a little bit slowly and just be 100% sure that that product is safe, doesn’t cause any adverse events. And then you can move more quickly. So that’s why, just as Amy said, it takes some time for us to be sure that we have both safety and effectiveness data.

[0:32:47]

RICK WEISS: Our next question touches again on that regulatory side for either of you. It’s from Tina Saey at Science News. How long does immunity need to last before a vaccine would be considered viable? And maybe I’ll add to that. There’s another variable, which is how effective it is. We all know that not – a vaccine may be somewhat effective. We know flu vaccine effectiveness varies year to year. Does how long they last and how effective they are play into some algorithm for making something approvable?

JOHN MASCOLA: I think we could use flu as an example, perhaps, because flu is not an ideal vaccine because, as we all know, we have to get it every year, and we have to change it often. So it’s sometimes 50% or 60% effective, and we have to get it every year. And yet, we use it, and it saves tens of thousands of lives every year. If it were better and 100% effective, that would be, of course, much better, if it lasted 10 years and we didn’t have to take it. So I think it would be similar with a coronavirus vaccine. If we could get up to 60% – and there are epidemiologists who model this kind of thing – at some point in time – at some point above 60%, you begin to give the virus problems to spread because every time it seeks a new host, you know, most of the time, that host is immune. So when you get into that range, you have a pretty good vaccine.

[0:34:12]

RICK WEISS: Great. Let’s see. A question here from Christine Herman at Illinois Public Media. Are there multiple vaccines going through clinical trials right now? And if so, does that mean that if one fails, a different one will likely turn out to be safe and effective? In other words, if the trial that’s starting proves ineffective, will there still be hope that one of the other vaccines in development will turn out in parallel production?

JOHN MASCOLA: So, yes, definitely. That’s the hope – that anytime a disease arises that’s a new disease, we should be a little bit cautious about what we know and what we think we know. And while, as I said before, there’s some enthusiasm that more than one type of vaccine should work based on what we know, it’s a much safer bet, especially when we’re in the middle of such, you know, a really aggressive pandemic, to take two or three or more what we call vaccine candidates and vaccine platforms together in parallel. It’s possible one of them doesn’t make it for a number of reasons. Maybe it’s hard to produce. Maybe it has some adverse side effects. Maybe it just doesn’t work as well as another. So just what you said, I think the answer to your question is, yes, definitely. If one doesn’t work, the others would still proceed, and the best ones will arise and be used.

[0:35:25]

AMY JENKINS: I think I’ll add to that. On the antibody front, we have – are taking a similar approach. There are several companies and groups that are moving forward antibody products right now for the same reason – that they’re all different antibodies. Nobody’s making the same one. We don’t know exactly how well each of those will work. Additionally, behind the scenes, we are still finding new antibodies every day. So we’re ensuring that we have kind of a continuous pipeline of these to move into manufacturing as we start to see how the other ones are working. And if we see that some are working better than others, we can very quickly potentially shift our focus to maybe an antibody that binds in a different way or that is a slightly different format – that we can then shift and start using and making more of those as well. So it’s a similar story on the antibody front.

[0:36:11]

RICK WEISS: And both of you have hinted that, of course, the next, final stage of that is the manufacture, or scale-up and manufacture. And that’s the focus of this next question from Sheila Eldred, freelance reporter. How confident are you that the manufacturing supply chain will be ready by the same time a vaccine is ready? Will we need more than one vaccine for that reason? I guess getting at the question of, if we don’t have the manufacturing capacity to really produce hundreds of millions of doses of a certain vaccine, do we want to get more than one going at the same time? John, you want to start with that?

JOHN MASCOLA: Sure. I’ll start with the vaccine side, and I’m sure Amy can comment on the antibody side. So this is a major area that needs to be addressed – it is being addressed – which is – I’ve talked mostly about developing a vaccine and showing that it’s effective, but if we’re fortunate and we get to that point, let’s say at the end of this year, the current thinking and plans are that in parallel, the U.S. government is working with several vaccine manufacturers in parallel to scale up their technology so that the vaccine would be ready in large quantities about the same time that the vaccine trial is done. And while – so it is possible.

And I guess the other part of your question is, yes, it makes sense to have more than one vaccine and more than one type of vaccine manufacturer because that addresses the issue of having to vaccinate 300 million or 400 million people in a country or, you know, several billion people in the world. And the only way that’s done is to have vaccine manufacturing capacity in different companies in different places and different regions of the world. So that’s being considered and thought about not only in the U.S., but by the WHO, by organizations like CEPI and Gavi that are really already thinking about this vaccine scale-up issue.

[0:38:11]

RICK WEISS: You know, I’m going to take the prerogative here and just add something onto that question. I mean, I’ve read this – that, you know, multiple manufacturing streams are getting ready so we can take the winner and run. Does that mean that entire factories are being built, buildings are being built and facilities are being built that can produce a vaccine that may never get used but at least that was part of a gamble? Or are we just talking about something a little more digital than an analog, solid piece of property?

JOHN MASCOLA: No, this is nuts and bolts of vaccine manufacturing. So whether – it may be a new building in some cases. Or in other cases, it’s prioritizing existing manufacturing capacity to be used for COVID-19. It may mean it’s being used in priority over something else. But – and that is, as you’re suggesting, Rick, it’s done at risk. It’s possible that that investment would be made, and that vaccine turns out not to be useful. But it’s thought to be – you know, you don’t take risks in phase three trials with safety and doing the trial robustly. But to take a risk with money, where you have a lot of vaccine available just in case, that seems to make more sense.

[0:39:17]

RICK WEISS: Great. I have a follow-up here from Rosemary Westwood at WWNO, I think for Amy here, again, in New Orleans on the antibodies treatment point. Is this going to be used in hospitals in tandem with plasma therapy, do you think? Or could it eventually replace it?

AMY JENKINS: I think that the hope would be that it would eventually replace it, likely because you can give this to a lot more patients. So you don’t need that essentially one-to-one or maybe one-to-two-or-three donor relationship to the person that’s receiving it, whereas we can grow it up and give it to a lot of other patients. So the hope is that we would be able to potentially – it’s likely that the convalescent plasma isn’t going to necessarily go away. We’ll – we may not entirely stop using it. But our hope is that we can start potentially treating a lot more patients with these antibodies in the meantime.

And we would be giving these to – initially to patients that are in hospitals that are what we would consider moderately or severely ill. We could even consider giving these to patients that are outside of the hospital but still sick – that would kind of be the next level of treatment – to see if they get better and see if they help them. And then we would move to that next phase, which is to give these to those people who are healthy but that we don’t want to get sick. And that would also be an opportunity to give that to those folks as well.

[0:40:41]

RICK WEISS: Next question is from Katie Jickling at VTDigger in Vermont. A lot of these therapies aren’t being vetted as thoroughly as they would have otherwise been. As reporters, what are the questions we should be asking to gauge the efficacy of these products?

AMY JENKINS: So I will say that, similar to what John was describing, these technologies are still absolutely being vetted. What we are doing is, again, manufacturing and doing a lot of the things that you would wait to make sure that it was a good molecule, that it actually worked before you started manufacturing, before you started putting a lot of money into growing this up in large bioreactors. There’s a chance that these may not work and we have to dump out all those bioreactors, and that would be kind of a sunk cost. But I think that that is a risk and an approach that we are willing to take now to have these available. But these technologies – I will say they are human proteins, so they’re things that naturally circulate in the human body. They are fairly well used for other indications. So we use them routinely for cancer therapies right now. We use them routinely for rheumatoid arthritis. There even is an instance of a licensed product right now that’s used in premature infants.

So these are generally regarded as safe. Of course, that’s not always entirely true. And they are being vetted in all of the kind of preclinicals while in the laboratory assays that they need to be vetted in. And additionally, they’re being vetted by our regulatory agencies. They’re looking at all of this data and ensuring that everything that these packages that are being provided are providing the right amount of data, that they’ve actually looked for the right efficacy signal or things like that in the lab and in animals. So I feel that they are being vetted. Where we are really taking a risk, again, is in that manufacturing. We may have to dump out a lot of product that showed not to be effective. I am, again, less concerned about safety in this instance as I am it just not working.

RICK WEISS: John, anything to add there?

[0:42:51]

JOHN MASCOLA: You know, I would just highlight what Amy was highlighting, which is that going quickly does not mean taking risks with regard to patient safety. So going quickly is done in other ways. It means, you know, making things in the lab quickly and manufacturing quickly. But the initial steps for assessment in people is done the same way that we’ve always done it – in phases with regulatory agency approval. So I think people should be assured about that.

[0:43:18]

RICK WEISS: What about testing the product that’s been manufactured? So you’re cranking out huge amounts of vaccines, maybe tens or hundreds of millions of doses. Isn’t there a process that has to happen to test the purity and manufacturing practices and so on? Is that speeded up as well?

JOHN MASCOLA: No. I think – so those processes, which are very sort of arcane processes to most people – we call them in our world chemical, manufacturing and control, meaning you have to understand everything about the chemistry and the manufacturing and all the controls on how you make it. That documentation has to still be done and submitted to a regulatory agency to say, here’s a batch of product. Here’s how I made it. I can prove that I made it according to your guidelines. So there are no shortcuts. One thing that goes more quickly, maybe, that the regulatory agencies prioritize COVID and say, we’re going to look at this information because it’s an emergency, and we’re not going to wait a few months and look at something else.

[0:44:17]

AMY JENKINS: Rick, the one thing I’ll add to that additionally is that you may be saying, well, then if you traditionally took all these years to do this, how come all of a sudden during this pandemic we’re able to do this so fast? John’s absolutely right. We don’t change anything about how we manufacture and how we ensure that that material is safe and clean and pure. What we did was we actually found these a lot faster. We literally found them in a matter of weeks, whereas it could’ve traditionally taken many months. So we were actually looking at beginning this process of manufacturing way back early in March, before we were really sure that we had the right one. There was a lot of things done at risk there. But it was that find that we shrunk that time frame, that discovery time frame, the science time frame on the very front end.

[0:45:06]

RICK WEISS: Got it. Great. Here’s a follow-up from Sean Hamill at Pittsburgh Post-Gazette. John, you might be in best position for this. What do you think of the five vaccine efforts by the five companies the federal government has targeted for additional financial support? Do they appear to truly be the best candidates, or do they appear to have been chosen simply because they are the furthest along?

JOHN MASCOLA: Maybe two parts to that answer. One is that, you know, there are a lot more than five candidates are receiving federal government support. So I think people should be aware that whether it’s the National Institutes of Health, the Department of Defense through DARPA or other parts of the DOD or whether through the organization called BARDA that actually funds advanced development, the Biodefense Advanced Development Research Authority (ph), there’s a lot more than five vaccines. What I think – what is being referred to here is that in the advanced development part of it that there are several that are furthest along. And, yes, they get the larger part of support because the vaccines that are most – are the furthest along in clinical development are the ones that are getting close to phase three trial. And those three trials are expensive, and they take a lot of manufacturing, so they get the highlights of the support. But, you know, part of that is that the federal government’s support is an ongoing process. So there is a continuing effort to look at other products in the pipeline that may merit the more advanced funding that has gone to the first – the handful that are furthest along.

[0:46:40]

RICK WEISS: Robin Lloyd at Scientific American – I’ve seen some reports that suggest convalescent antibodies are not as effective as hoped against SARS-CoV-2. How does this fare, if at all, on the DARPA antibody approach?

AMY JENKINS: Yeah. So it’s interesting – right? – because when you give convalescent plasma, you are actually giving all of the antibodies. So you’re giving what I like to say is the good, the bad and the ugly. You get everything in there. And so our hope is that when we go in and we pull out just the good and we can give a very high concentration of this just the good that it would be even more effective than the convalescent plasma. I think there’s at least some data, and if – even if it’s just anecdotal, that in some cases, the plasma does help. So, again, the other thing to consider is that every time plasma is given, it came from a different patient.

So it wasn’t – it’s not necessarily standardized. It was a different person’s immune response every time it’s used. And person A may have made a wonderful immune response and they may have had a lot of the good in there, and so that may have gone very far in treating a patient that received that plasma. Patient B may have made an OK response and it may not have as much of the good. It had enough good to meet the bar of being a donor, but it just made – there’s a lot of disparity amongst the two different types that are given. So our hope is that by going in and pulling out just the good and giving back a high concentration of the good that it will be even more – much more effective.

[0:48:07]

RICK WEISS: Super clear, thank you. Nicondra Norwood at WVUE TV Fox 8 in New Orleans – how does virus mutation play into development of treatment and vaccines?

JOHN MASCOLA: Maybe Amy wants to start on treatment.

AMY JENKINS: I’m happy to start. So it is a risk. It is absolutely a risk. It is something that we try to find those antibodies. So, as you saw in John’s slide, there’s that spike protein on the surface of the coronavirus, and that interacts with our cells and gains – helps the virus gain access to our cells. What we do with the antibodies is we try to find those that bind on that spike protein, but they bind in a very specific spot. So an antibody is actually a fairly large protein. I mean, it just gets in there and blocks it. It just – the virus can no longer access your cells. And so it will bind to that very specific spot. And we’ve actually looked for those antibodies that bind to those very specific spots. But there are some regions on that spike protein that don’t seem to mutate as much. And so what we have done is a concerted effort to find the antibodies that bind to that region that doesn’t mutate as much so that if it does mutate slightly somewhere else, it won’t matter because it mutated – it did not mutate in the place that our antibodies recognize. So that is the approach we’ve taken.

Our groups have looked at the place where the antibodies bind and looked for all of the known mutations to date in that region where that antibody binds, and they have not seen any mutations that would indicate that this antibody will no longer bind. It’s always a risk that something will happen and there is a mutation that would garner some of these – that would make some of these antibodies not as effective. And in that instance, we are actually finding more antibodies. We’ll have those in the pipeline. We’ll have those ready to go. Finally, the other approach we’re taking is that, in some cases, rather than just giving one antibody, you can actually inject two. And so you can have one that binds somewhere and one that binds another place. And if, for some reason, the virus mutated in a place where one of them bound, the other one is likely still effective. And so you’ve now just increased your likelihood that you’re going to still be able to bind the virus by giving two antibodies. And several of our groups are doing that. They are actually looking to give two antibodies, not just one.

[0:50:34]

RICK WEISS: A question here from Sally Squires, former workmate of mine from The Washington Post, now a freelancer and contributing for WTOP. Is there any concern that the COVID efforts will affect the production of flu vaccines or other vaccines?

JOHN MASCOLA: I mean, I’ll try to answer that. I don’t know formally in the sense that I can’t speak for the companies that make flu vaccines. But I haven’t heard any concern in that regard. I think the flu vaccine manufacturing capacity is very tried and true. It happens every year. The companies have that infrastructure. And my best understanding is that the infrastructure being used for the COVID vaccines is new infrastructure that wouldn’t impact that.

[0:51:17]

RICK WEISS: All right. Question from Charlie Schmidt at Scientific American. What’s the latest on the challenge trials, the idea of deliberately infecting people with SARS virus to see if the vaccine works? Is that in the cards?

JOHN MASCOLA: I guess I can start on that and Amy can augment if she wants. There’s a lot of discussion on that. A couple things would need to be in place. So the general consensus is that if we had a treatment for this virus – a therapeutic treatment, an antibody that Amy’s working to develop, or a drug – that would make it a lot more straightforward to use human challenge models, where you can learn a lot. You could do a study to see if you infuse an antibody, does it protect against challenge? If you deliver a vaccine, does it protect? But we’d really like to have a little bit more knowledge about the virus and a very specific treatment.

RICK WEISS: Anything to add there, Amy?

[0:52:05]

AMY JENKINS: No. I think we have utilized, and our hope is to be able to utilize these types of models for other infections, such as influenza, ’cause there are challenge models for those. One of the additional complexities is when you’re developing these types of approaches is that you actually – you’ve heard John and I talk a lot about manufacturing. You now actually have to learn how to manufacture virus under those same stringent conditions that we would make the therapeutics and the vaccines. And so it’s called good manufacturing practices, and you have to learn how to make virus, which is a living – somewhat living – it’s a dynamic molecule. And so we need to – that adds a level of complexity in developing those potential challenge programs.

[0:52:52]

RICK WEISS: The oxymoron of good manufacturing practices can make bad viruses – sounds like a challenge. Nina Pullano, a reporter at Inverse in New York – for Dr. Jenkins, can you give a brief overview of the role of animals in COVID-19 antibody research? Does it seem likely that we could use animal antibodies to treat humans? Thinking about research on the camelid antibodies, in particular, from MERS.

AMY JENKINS: Yeah, that’s a great question, and we often do think about that. And I have to be honest. We prefer human antibodies because they’re human and we know that they circulate naturally in the body and your body won’t – could recognize them as somewhat foreign but is likely to not recognize them as too foreign. They circulate for a long time, and they last a little longer. With animal antibodies, we do – there are animal antibodies that are licensed products. We do something to them called humanizing them, so we make them look a little bit more like a human antibody, and we absolutely could do that. We feel that the human approach is maybe a bit more robust at this point. And because we can find them very quickly, we prefer to go this way.

I will say that in the early days of the outbreak, when there weren’t U.S. patients or maybe we didn’t know about U.S. patients yet, there was a lot of discussion, and we actually did initiate the potential for giving this virus and infecting animals with the virus and then beginning the process of finding antibodies out of those animals. We did that as just a, let’s hold this in case we have a hard time getting humans that are willing to donate their blood. So it is absolutely a valid approach. It’s something that we do as part of our program. We have groups that can find antibodies from animals. Related to your specific question about camelid antibodies, camelid antibodies are a special type of antibodies that alpacas and some other animals make, and they’re shaped a little different, essentially. They’re very novel, and we have done extensive studies on those antibodies. We have found those antibodies in previous trials at our – as part of our program.

The concern with those, oftentimes, is twofold. The first is that they look quite a bit different than what we would consider are human antibodies. So we are concerned that your body would see them as foreign and maybe take them out, if you will. The second is that because they’re not fully human, they don’t last in our blood as long. And one of the big advantages of antibodies is that you don’t have to take it day in and day – like, think of an antibiotic. You have to take that sometimes three times a day. An antibody, you can typically get an infusion, and you’re good for a couple months. We’re not quite sure how these camelid antibodies – how long they would last, but they certainly wouldn’t last for many months. They’re a little bit more akin to that thing that you have to take quite frequently.

[0:55:38]

RICK WEISS: Great. We’re almost out of time. I want to get one more question in here, and this is an interesting one from Betsy Ladyzhets at Stacker, which is based in New York. During the COVID-19 pandemic, disinformation and mistrust in science have spiked in the U.S. What can journalists do to ensure that when vaccines and antibody therapeutics come out on the market, people are actually willing to use them? John?

JOHN MASCOLA: I can – sure, I can start on that. I think, you know, journalists can reassure in their writing that this is a scientifically based process that is very similar to the process that happens all the time, just all the things we described – very careful scientific discovery, very careful manufacturing, very careful regulatory authorities, very careful clinical trials. And that’s happening with COVID because, especially with regard to the scientists involved and the federal government people involved like Dr. Jenkins and myself, we wouldn’t have it any other way.

AMY JENKINS: Yeah, I think the only thing I’ll add there is that, as John can attest to, we spend hours – hours – on the phone and in rooms discussing the concerns. What can we do to ensure that this is safe, that we’re doing this right? This is not something that is rushed into lightly or is taken lightly. We proceed with extreme, extreme caution on the safety and the efficacy of these molecules that we’re trying to develop.

[0:57:06]

RICK WEISS: Thanks. I’m going to give you each just a half-minute here as we wrap up to sort of give a final take-home message or any sort of final point that you’d like to make for our reporters online today. John?

JOHN MASCOLA: Sure. Thanks, Rick. I would emphasize that the overall public investment and the public-private sector investment in coronavirus vaccines is enormous. It’s been fast. It’s been focused. And I think that should be reassuring to people that this all-out effort will result in a vaccine that is made available to the public. And we’re just going to see how quickly that we can get there.

RICK WEISS: Thanks. And Dr. Jenkins.

[0:57:44]

AMY JENKINS: I think that I will end by saying, not to sound too pessimistic, but this will happen again. And I think that this is a learning opportunity for us. We are moving, again, with all safety and efficacy in mind. But we are moving quickly. We are moving methodically. And we are learning lessons. And my hope is that in the future, we’ll apply these lessons so that the next time, we can move potentially even faster and with a bit more elaborate (ph).

[0:58:11]

RICK WEISS: Great. I want to give a huge thanks to our two speakers today from all of us. I want to remind the reporters on the line that the video and transcript of this media briefing will be available on the SciLine website within the next day or two. I also want to strongly encourage reporters who are online to take just the 60 seconds it will take you to answer the three-question survey that you’ll get as you log off today. It really helps us do a good job on these briefings going forward. Thank you for taking that minute to help us help you. I encourage everyone to check out our website, sciline.org, and follow us on Twitter, @RealSciLine. And thank you all again for this very informative media briefing today. So long for now.