The Challenging Path To A COVID-19 Vaccine
This story is part of Science Friday’s coverage on the novel coronavirus, the agent of the disease COVID-19. Listen to experts discuss the spread, outbreak response, and treatment.
Over 50 pharmaceutical companies and biotech firms around the world are now racing to develop vaccines for the coronavirus responsible for COVID-19. Anthony Fauci has said that it might be possible to develop a vaccine in as quickly as 12 to 18 months—but so far, researchers still don’t know which of several approaches might be most safe and effective.
Paul Offit, head of the Vaccine Education Center at Children’s Hospital of Philadelphia, says that usually, the standard time to develop a new vaccine and move it through the multiple phases of clinical trials required for FDA approval is measured in years, not months—and despite the need, he worries that shortening the path to a vaccine means that developers will skip critical parts of the testing process.
He joins Ira to talk about the path to a vaccine, and how it might fit in with other parts of the coronavirus response, including community testing and the development of therapeutic drugs to treat patients with COVID-19.
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Paul A. Offit is the author of Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine (Harper, 2013) and chief of the Division of Infectious Diseases at Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. A bit later in the hour, a salute to the Hubble Space Telescope, which launched 30 years ago today. Seems like yesterday. Right?
But first, a key part of plans to return to normal post-pandemic life is the availability of a vaccine against the Coronavirus. Many drug companies and biotech firms have plunged into efforts to rapidly develop and test potential vaccines. Experts such as Dr. Anthony Fauci say it may take 12 to 18 months to bring a working vaccine to market, but is that timeline overly optimistic? Is it real? What about it? And just where does having a vaccine fit into our overall response to the Coronavirus pandemic?
Joining me now is Dr. Paul Offit, Director of the Vaccine Education Center, and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
Welcome back, Dr. Offit.
DR. PAUL OFFIT: Thank you, Ira. Good to be back.
IRA FLATOW: First, walk us through the process of what needs to be done before a vaccine can be available. What is the testing process, the research process? What goes on here?
DR. PAUL OFFIT: Well, typically what’s done, and this is a virus that we just got in hand a few months ago, is you have to make a decision about how you want to make the vaccine. Do you want to take the virus and activate it as the way that the polio vaccine or hepatitis A vaccine is made? Do you want to take a virus and weaken it the way the measles vaccine is made? Do you want to just take part of the virus, just one protein from the virus, which is the way the hepatitis B vaccine is made? Or do you want to do a completely different strategy, like a genetic strategy, DNA vaccine, messenger RNA vaccine?
So once you’ve made that decision, then usually you do extensive animal model studies, so-called proof of concept studies, where you have an animal that, for example, gets sick with this virus, and then you try a variety of different strategies to see if you can protect them from getting sick.
With that, then you go into phase one, phase two trials, which are progressively larger safety immunogenicity trials, remembering that you don’t really know exactly what immune response is protective yet. The only way, really to know that is to do a large, placebo-controlled safety and efficacy trial, which often involves tens of thousands of people.
The typical length of time it takes to make a vaccine is 20 to 25 years. I mean, our vaccine, the rotavirus vaccine, was made in 26 years. So that’s the typical amount of time.
When you’re talking about trying to get a vaccine out there in one to two years, you’re definitely talking about skipping parts of this process. So the question is, which parts are you skipping?
IRA FLATOW: Is this risky, are you saying now, by skipping these parts of the process that we’re doing with this vaccine?
DR. PAUL OFFIT: I guess what I’m saying is I can’t see how it would be possible to know in 12 to 18 months that you have in hand a vaccine which has been tested in tens of thousands of people, pre-licensure, then submitted to the FDA for licensure, and then licensed, and then commercially available.
What I would imagine is that a much smaller number of people would be tested pre-licensure if the vaccine even was to be licensed. I mean, is this vaccine going to be licensed by the Food and Drug Administration?
I guess we’ll see how this plays out, because won another option is that you just do sort of very small safety immunogenicity trials. You find that you get an immune response that you think is likely to be protective, but you don’t know that yet. And then you just slowly roll it out. And then once it’s as a commercially-available product, that’s when you see to what extent it works, or to what extent it’s safe. Which I hope we don’t do it that way. I’d like to think we’re going to do large-scale, placebo-controlled, safety efficacy trials before we roll it out, because if not, then we’re taking somewhat of a risk.
But again, it’s always risk benefit. I mean, if this virus is COVID 19 is still a scourge that, and it’s still killing thousands of people, the risk benefit ratios change.
IRA FLATOW: It seems like there are so many different companies, so many different vaccines being tested. Is there no standard way to make a vaccine?
DR. PAUL OFFIT: No. You’d see what works for that particular virus. So you’re right, though. There are more than 50 companies across the globe that are making this vaccine. That’s the good news. There’s clearly a lot of interest and money in doing this. So that that’s not an impediment.
But how are we going to make it is still not clear. And if we choose the DNA messenger RNA approach, so the way the messenger RNA approach which works, which is now a BARDA, which is part of Health and Human Services, just put $483 million dollars behind this vaccine. So that’s obviously a strategy they like.
What that does is you inject the person with messenger RNA, which is then translated to the protein of interest. In this case, the protein is that spiked protein that sits on the surface of the virus. That’s the part of the virus that attaches to cells. So if you can prevent that virus from attaching to cells, you can prevent infection.
That’s the good news. So you’ll see whether or not this approach could work in people. But again, we don’t have a messenger RNA vaccine. This would be the first vaccine like it of its kind. So you would like to test it in tens of thousands of people before licensure. But if you’re going to do that, then we’re not going to have a vaccine as quickly as people would like.
IRA FLATOW: Why not take something like the Ebola vaccine, which we have developed, and just chop off pieces and use that?
DR. PAUL OFFIT: Right. So the Ebola vaccine was made by a so-called vector vaccine approach, which is you take, in this case, a different virus. In the case of Ebola it was something called vesicular stomatitis virus into which was cloned, then, the gene that coded for the surface protein of Ebola. So your argument is do the same thing here. Just take the vesicular stomatitis virus, and clone into it the gene that codes for the surface protein. That’s actually being done by a couple of companies. One of them is using not the vesicular stomatitis virus, but a different virus called adenovirus 29. I believe that’s Johnson and Johnson’s approach.
Again, it’s all be determined in terms of whether it’s safe and effective, because you never really know whether a vaccine is safe and effective until you do a large-scale safety efficacy trial. So hopefully that will be done for these vaccines so the public can have as much information as possible before being asked to be injected with it.
IRA FLATOW: There was a study that has not been peer reviewed, but has been published, that shows a study of blood samples of 3,300 residents who live in Santa Clara California, which is Silicon Valley. And it concludes that the infection is much more widespread than indicated by the number of confirmed cases. I’m just quoting from the conclusion.
That means up to 4% of the population has been infected. What do you make of these results?
DR. PAUL OFFIT: Not surprising, because who do we test? We generally test people who are mildly or moderately or severely ill. We don’t test people who have no symptoms. But we know that certainly from the data that initially came out of China, that as many as 80% of people who were infected with this virus either have no symptoms or mild symptoms, so that a much larger percentage of the population has been infected than we think makes sense. And those data have also been confirmed by studies in Germany, studies in Iceland, So I don’t find them at all surprising.
I think some people may be falsely reassured that that’s the best way to develop a population immunity is just to have people naturally infected. But the only real way to develop true population immunity is with a vaccine. We’ve learned that with measles.
I mean, every year measles would cause 2 to 3 million cases in this country. The only way we eliminated measles from this country was with a vaccine. And remember, when you’re naturally infected with measles, which people who are as old as me were, you’re protected for the rest of your life. Yet still that wasn’t enough to stop the spread of that virus until we got a vaccine.
IRA FLATOW: Yeah that would also mean that there are many more people walking around than we thought who are not showing any symptoms.
DR. PAUL OFFIT: Right, and who are immune. And so it would be great, I think, as we’re trying to avoid the second part of this nightmare, which is the massive joblessness and massive of homelessness that comes with massive joblessness and all the health problems associated with that, to get us back to work. And one way to do that is to do wide-scale testing to see who’s infected, wide-scale testing to see who’s protected, so we could be much smarter about getting back to work, which is basically, I think, what Governor Cuomo is trying to do in New York. And it’s what people have done in Germany. It’s what Angela Merkel has done in Germany. So that’s the best way to do it.
IRA FLATOW: So then this testing is still really a great priority.
DR. PAUL OFFIT: Definitely. Absolutely key.
IRA FLATOW: And how fast do you think we can actually get enough tests out there?
DR. PAUL OFFIT: So we have the capacity to do that. I think what we need to do is make sure we have all the reagents like the viral transport media, the swabs that needed to be out there. And that’s where the federal government can help a great deal.
I think the president is right when he says that the governors or people locally should make the decisions, because they know their districts and territory is the best. But the federal government can clearly play a role in making sure that everybody has what they need in terms of getting the testing done.
IRA FLATOW: If we do get people and we do test them and we find out that they have been exposed, how sure are we that that means that they’re protected from getting it again?
DR. PAUL OFFIT: So there were studies done with human coronaviruses years ago. And looking, they were actually experimental challenge studies, looking at people who were challenged with one of the four types of human coronaviruses that circulate every year in our country, and then challenged them a year later to see whether they were protected, and they were.
So I think it’s fair to say, given the type of virus that this is, that if you’re naturally infected with the virus, that you’re probably going to be protected against it for years.
And the good news also about this virus is that although it’s a single-stranded RNA virus, it doesn’t appear to mutate. This is not flu. I think this is going to be more like measles or mumps or German measles where it’s going to be sort of a single serotype disease, which then could be prevented, and we don’t have to worry about it being a moving target like influenza is.
IRA FLATOW: We’re seeing some governors who are now opening their beaches, and they’re taking off their restrictions. Is that possible in this? Or are they just playing with fire here?
DR. PAUL OFFIT: We’ll see. I mean, you do have sort of control groups, if you will. I think New York is taking more of an approach similar to Germany where they want to do testing to see who’s infected, see who’s immune before you send people back out. And when you send them back out, you sort of test the water with one foot, if you will. You just send back say one particular segment of an industry and see what happens, and then move forward slowly and slowly. As I think from just reopening things, as seems to be happening in states like Georgia or Florida or Texas.
And so I think in a few months we’re going to know what the right approach was, and how better to do this. But in a sense, it’s like an uncontrolled, natural experiment.
IRA FLATOW: So what? I was going to say that we’re just having a human population experiment.
DR. PAUL OFFIT: Right. And we’ll learn from it. I suspect in some ways we’re going to learn the hard way.
IRA FLATOW: What would you have done differently than the way we’re doing things now in terms of developing a vaccine, or in terms of developing therapeutics?
DR. PAUL OFFIT: I think there’s an enormous amount of interest and energy in looking both at antivirals. I think we can say now that hydroxychloroquine is not what it was hoped to be. But other drugs, like remdesivir or favipiravir or lopinavir antivirals, which good should work here. We’ll see whether they work. There are a number of National Institutes of Health Associated trials, prospective controlled trials. And I think we’ll know really in the next week or so to what extent those antivirals are of value.
Regarding a vaccine, again, I think there is an enormous amount of interest in doing it. The CDC, the Food and Drug Administration, academics are very interested in making sure this vaccine moves forward. And we’ll see how it plays out.
Moderna, which is this mRNA vaccine, seems to have the lead. The DNA vaccine made by Inovio, which is a Plymouth meeting company, also is now in human clinical trials. I think we’ll see how this plays out.
There certainly is the scientific expertise to do it. There certainly is the money to do it. The question is how much testing do we want in-hand before this vaccine is commercially available? And that is, to some extent, going to be determined by to what extent this virus is still a scourge six months, 12 months, 18 months from now.
IRA FLATOW: Dr. Offit, thank you very much, as always.
DR. PAUL OFFIT: Thank you, Ira.
IRA FLATOW: Paul Offit, director of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children’s Hospital in Philadelphia.