Voices of the Virus

Is a Vaccine Really Coming?

It will take a while, says Yale’s Gregg Gonsalves. And when it comes—the government must consider setting the price.

By Gregg Gonsalves

Tagged COVID-19Health CarepandemicpatentsPharmaceutical Industryvaccine

For this installment of our “Voices of the Virus” series, Editor Michael Tomasky spoke with Gregg Gonsalves, assistant professor in epidemiology of microbial diseases as well as an associate (adjunct) professor of law at Yale Law School. His research focuses on the use of quantitative models for improving the response to epidemic diseases. For more than 30 years, he worked on HIV/AIDS and other global health issues with several organizations, including the AIDS Coalition to Unleash Power, the Treatment Action Group, Gay Men’s Health Crisis, and the AIDS and Rights Alliance for Southern Africa. They spoke on August 10.

Michael Tomasky: Let me start with a general question. You wrote recently about the vaccine development process. Just give our readers a sense of where you think that stands right now.

Gregg Gonsalves: A couple of things. One is that the progress for the vaccine for infectious diseases usually takes years, often decades, or, in the case of HIV, for instance, it’s still a sort of distant dream. And so the idea that we’ve been promised a vaccine by the end of this year, by October, November of this year, even by early 2021, seems sort of wildly optimistic.

The second thing is that there are bits and pieces of the vaccine enterprise that we can do at warp speed: scaling up pre-production of vaccines as many of the companies are doing, trying to ramp up clinical trial capacity, as many companies and the U.S. government are doing. There are operational pieces of it that we can expedite and compress. What you can’t expedite or compress is the serendipity of discovery. Putting together a vaccine is not an engineering problem where you’re just putting the parts together and watching it run. It’s an iterative process of discovery in which we’ll find out whether the pieces of the virus that are being used to elicit a response are the right ones. All that stuff, we can make our best guesses, and that’s what many of the companies and countries have done, but there’s no guarantee that it’s right. And this is where we are today.

MT: Why does a vaccine process usually take years?

GG: The immune system is complicated. It sounds like a joke, but it is. Figuring out how to elicit an immune response to protect against an infection is a hard task, particularly for viruses that are so adept at manipulating the immune system. And in the context of pandemic diseases, like SARS and others that appear and go away, we often don’t have a concerted effort to develop them or even the ability to test them.

So even if you know what the correlates of immunity are—that is to say, you know you need to raise an antibody to this part of the virus or generate a T-cell response to another—the idea that you’re going to be successful in generating a vaccine that can elicit this exact kind of response is not a given. But we don’t know what the correlates are to community, or what protects you against natural infection with SARS-CoV. We have no idea. The immune response is the innate response, the antibody response, the T-cell response; it’s a very complex suite of immunological reactions to pathogens. We don’t know what protects, so we’re sort of throwing everything at the wall and seeing what happens.

What we’ll find out from the trials is that…we’re hearing, “Oh, they’re promising, because they raised antibodies to this. We can show responses to that.” If those vaccines turn out to be effective, like even partially, we’ll know we’re on the right case, but if we find out that actually it raised antibodies to this epitope or T-cell responses to this other epitope, we may find out that our best initial hunches were wrong. So part of it is going to be that we need to learn more about the virus we’re dealing with and the immune response to it. We’re only eight months into it, into our knowledge of this new disease.

MT: Is there a legitimate scientific reason why we might be able to get a vaccine faster in this case than normally happens? Is there something about this pathogen?

GG: No. I think the one thing you can say is that there is enormous effort and resources being thrown at this. It’s not like it’s an easy virus to make a vaccine against. We don’t have a vaccine against coronavirus at the current moment. So it’s a challenge. The other thing is that even people like Tony Fauci and others are talking about how this vaccine is going to be partially effective, if at all. So we aren’t going to do it sort of one and done, right? We’re probably going to see an iterative process, in which we fail, we fail, we fail, we succeed a little bit, we improve and make a better vaccine, with this taking quite a while to sort of run its course, over years rather than months.

The other thing is understanding that if this vaccine works, the ones that are out there in the field right now, they’re going to go into tens of thousands of patients. And the simple idea is that there are two groups, one gets placebo, one gets the vaccine. And you want to see more infections in the placebo group than in the vaccine group. But it means that people who are in the trials, they’re going to have to be in situations where they’re going to encounter the virus so that we can accrue these sort of endpoints, as they’re called in clinical studies. It’s not quite sure that we’re going to see these end points accrued rapidly based on the sort of natural shape of the epidemic in the United States and where the clinical trials are and where the people enrolled in the clinical trials are. In some places, in Europe and in China, where the virus is more under control, it’s going to be harder to do the studies because there are less infections.

MT: What would be a good success rate for a vaccine?

GG: You know, I get the flu vaccine every year. I hope you do too. Those vaccines are often, you know, maybe 65 percent effective. Remember, when you think about vaccines, it’s not just about how effective it is for you or me, but how many people take it, right? And so a 65 percent effective vaccine could be great if we could get 70, 80, 90 percent of people to take it because you have to break the chain of infection.

We hear all this talk about herd immunity. What vaccines do is create an artificial herd immunity based on a vaccine instead of natural infection. When we’re talking about herd immunity, we’re talking about 60, 70, 80 percent of the population having a protective immune response against the virus. So even if it’s not a robustly effective benefit, we might be able to blunt the epidemic.

MT: My understanding is that the lower the success rate of the vaccine, the lower that percentage, the more people you ideally want to take it, is that correct?

GG: You know, we see measles outbreaks and mumps outbreaks in the United States. Not because the vaccines are ineffective; it’s because not enough people have taken them, right? I mean, there are pockets of people who are vaccine refusers or have some objections to the vaccine and the herd immunity in their communities drops. So vulnerability is created across the community no matter if a few people are vaccinated. So you want to reach as many people as possible, particularly with these partially effective vaccines.

MT: So about a 60 percent success rate, or 65, would be maybe about what we could expect, probably?

GG: Who knows? It’s really hard to predict. I mean, people are talking about 60, 70, 80 percent coverage, but it’s not going to wipe SARS-CoV off the map. That’s the first step. Then we have to get it to people. Then we have to decide who gets the vaccine, who doesn’t get the vaccine, in the United States, around the world; how we’re going to make sure that people’s distrust of vaccines, which was very much alive in the United States before COVID-19, is overcome in communities that are perhaps afraid of vaccines for whatever reason or have been told myths about the vaccines that we have to dispel.

MT: So talk about that distribution process a little bit. First of all, I assume that whoever develops this vaccine is not going to be like Jonas Salk and refuse the patent.

GG: (laughs) No, no. But it’s interesting. The NIH has had some involvement in some of these vaccines. Moderna’s vaccine, for instance, my colleagues at NYU, Chris Morton and others have shown that vaccines do not [arrive] entirely without sort of a reliance on public support and public contributions.

MT: Well, the federal government has given Moderna hundreds of millions of dollars, hasn’t it?

GG: Billions of dollars. Two billion. And a lot of that’s about helping them to ramp up stuff, but they also provide intellectual support. So talking about patents and intellectual property and stuff like that, we’re going to need to do a lot of investigation of like, who owns the IP for what, because I do not think we’re going to see a Jonas Salk, the-vaccine-belongs-to-the-world moment. I think there’s going to be a rush to corner the market. And, there’s millions and millions of people around the world who’ll need it. Price will be an obstacle. And if that’s the situation we’re in, and we’re talking about a vaccine that’s $35 a dose or $20 a dose, that’s a joke, it’s automatically out of the reach of many, many people from places around the world.

MT: Can’t Congress set the price though? Can’t Congress just pass legislation to say you can’t charge more than X?

GG: Well, there are other things that you can do right now. So there’s something called the section 1498 in the U.S. code that says if the United States sees a compelling national interest, it can basically say to a manufacturer that we’re going to pay you a reasonable royalty, and we’re going to take the patent over, and we’re going to make the drug. We’re going to make it and distribute it to those who need it. So we don’t have to pass a bill. We could do it under current legal mechanisms. The armed forces does it all the time. They see a product they need, and there may be competing intellectual property claims on it. They can march in and decide that they’re going to pay reasonable royalty and then buy out the patent and make the product for their own needs. And they could do the same thing with vaccines and drugs. We just don’t do it.

MT: Well, if ever there were a compelling case to do it, I think this would be it, wouldn’t it?

GG: Yeah. My friend Amy Kapczynski at Yale Law School and others have been making the case about drug pricing. You could easily say drugs that have been outrageously priced, like the drugs for hepatitis C, for instance, to be a case for that—where there’s obvious price-gouging going on.

I work in HIV. The reason millions of people with HIV around the world have access to antiretroviral therapy is because we broke the patents and manufactured generic versions of these medicines. Brazil, Thailand, and other countries said, we are not waiting, we’re going to make these drugs ourselves. There’s a compelling national interest. And they decided to make the drugs on their own even if they were under patent in the U.S. to companies like Bristol-Myers Squibb or Gilead. This is how the revolution in the treatment of HIV/AIDS happened over the past 20 years. It wasn’t out of generosity and good will. It was the fact that Brazil, Thailand, and other countries said, you know what, we’re going to make the drugs generically through our public pharmaceutical industry. And we’re going to do it for our people. You’re going to start to see that happening. Like Remdesivir, the drug for COVID-19? There are companies that already can make it in India and Bangladesh and other places.

MT: So has the United States ever done that in recent history, to your knowledge?

GG: They’ve threatened it. Remember anthrax? After 9/11? Ciprofloxacin was a drug that was in short supply and expensive enough that the United States threatened to say you lower the price or we will make the drug ourselves, we will march in and take the patent. The company dropped the price.

I guess it was the Bush Administration. There were threats made back then. But, you know, the U.S. doesn’t like to do that: Property is sacred, intellectual property is sacred, and patents are sacred here. But South Africa, India, China, Brazil, lots of countries have their own public sector pharmaceutical industries or have tried to use the flexibilities in the World Trade Organization rules about intellectual property to say there’s a public health emergency. Intellectual property doesn’t need to be a barrier to getting these vaccines out to those who need them. Particularly if some company decides they’re going to charge more than a few pennies per dose.

MT: That’s really interesting. Let’s talk about politics and the President for a little bit. Obviously, he wants to push a vaccine before Election Day. Why would a manufacturer cooperate in that if it wasn’t ready, because it would destroy their stock price and destroy their reputation and so on?

GG: So, a couple of things. One is that Pharma, for a long time—not to go back into ancient history, but I was born in 1960. You remember thalidomide? We avoided the thalidomide disaster in the U.S. by an FDA official named Frances Kelsey, who refused to approve it in the United States. It led to the modern FDA where you have to prove that a drug is safe and effective before it can be used. And the pharmaceutical industry said, “Oh, you’re going to destroy innovation in the United States.” And they said it for 20 years, 30 years. And then in the eighties and nineties, they found new friends in the deregulatory right. So they they’ve been trying to erode the responsibility for proving that a drug is safe and effective for a long time. So we’re in a position where we know less and less about the drugs we put in our bodies and pay more and more for them year after year in the U.S.

So, Moderna, or one of these new companies that has never had a drug on the market—Moderna’s never had a vaccine on the market. So, two things. One is they may really think their vaccine works. And they may do some statistical analyses that show that it works. So they’d have a strong incentive to be the first in the game. And whether it’s through either their unbridled enthusiasm for their product or their unbridled greed, they’re not going to pay a penalty for it. They’re not going to pay a penalty for it unless the vaccine turns out to have serious side effects that hurt people.

If this first vaccine is mired in controversy about whether it works or not, along with people’s suspicions about vaccines and worries about side effects, we’re never going to get near the number of people needed to take the vaccine. There are already people saying in news reports that they won’t take a COVID vaccine. So we’re already facing an uphill battle. So we could have a big, hot mess in October or November where [FDA Commissioner] Stephen Hahn wants to pursue an emergency use authorization (EUA) for one of the vaccines because he’s pressured by the White House, and one of the companies decides to play along, with the idea that “We’ll submit our data later.” Right? And if you say, how could that happen? I just say, hydroxychloroquine.

Hydroxychloroquine is the warning for us because eight months later, we’re still talking about a drug that the President says works and most scientists say doesn’t work. And Peter Navarro and everybody else is on TV and in the press saying this is all conspiracy. Hydroxychloroquine is given to people who are sick or people who have a mild disease. What about a vaccine that needs to be given to millions of people who are not sick or not infected with the virus? Right. It’s a much bigger deal to have confusion and lack of trust around the vaccine than it is about this drug that hopefully none of us will ever have to take.

MT: What’s your opinion about Stephen Hahn?

GG: Two of the political appointees, Deborah Birx and Robert Redfield, are old AIDS hands. It’s pretty clear that Redfield collapsed early on. Birx collapsed, her integrity collapsed, shortly afterwards. Hahn let the hydroxychloroquine in on an EUA pass through. I think he’s a political appointee who has vulnerability. I don’t have faith that he’s going to make the right choice. I think they put out a piece in JAMA the other day that said they’re going to go by the book and do this in the right way. But could he stand the pressure of President Trump or somebody from the White House saying you’re going to do an EUA for this?

MT: Last question. One year from today, what will life in this country look like?

GG: Helen Branswell from Stat News wrote an article, it starts with “Winter is coming.” We have a few more weeks to reset our response to SARS-CoV-2. Because what we’re going to see this winter is not just SARS-CoV-2 in a resurgence. Many of us can do social distancing by virtue of just walking out our doors and spending most of our time outside. And when it starts to get cold and people are indoors, people are coming back into schools, the universities are starting to fill up, and then we have the common cold and influenza showing up in the fall? I remember Yale-New Haven Hospital was full of flu cases in December last year. Now add flu on top of COVID. Helen Branswell talked about a bleak, Dickensian winter. And even if Donald Trump loses, we’re unlikely to see a vaccine that’s able to offer as much protection by the time we even ramp it up and get it out.

Unless we really set the response we’re talking about perhaps another a hundred thousand deaths or more. You know, we’ve had this year of magical thinking, which is 2020. And we’re going to have a big wake-up call in 2021 because the idea that we’re going to be able to go back to school or go back to university or go back to work or do any of the things that we normally used to do is going to…the reality of it all is going to come crashing down. In January, if we have a new President, one thing he’s not going to do is spread disinformation and lies. But he’s going to be powerless to stop the wave of infections that have been generated over the past 12 months. So a year from now? Next summer, we’re going to look back and ask: Is there a whole lot of carnage in the United States that was utterly preventable? Yeah.

Read more about COVID-19Health CarepandemicpatentsPharmaceutical Industryvaccine

Gregg Gonsalves is an Assistant Professor in Epidemiology of Microbial Diseases as well as an Associate (Adjunct) Professor of Law and Research Scholar in Law at Yale Law School, co-director of the Yale Law School/Yale School of Public Health Global Health Justice Partnership and the Yale Law School/Yale School of Public Health/Yale Medical School Collaboration for Research Integrity and Transparency.

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