Everything You Need to Know About the Coronavirus Vaccine

The race is on to develop a coronavirus vaccine, but manufacturing and distribution may be an even bigger challenge.

A clinical trial participant is injected with a candidate coronavirus vaccine at Oxford University.

As the pandemic rolls on, universities, biotech companies and pharmaceutical giants around the world are racing to find a coronavirus vaccine. Taking a vaccine from concept to delivery is process that usually takes many years, sometimes over a decade, but scientists are hopeful they can develop and distribute a coronavirus vaccine in two years or less. Short of developing a successful drug treatment for COVID-19, finding a vaccine is the only path to a return to normalcy.

According to the World Health Organization, there are 76 candidate vaccines currently in development, five of them already being tested on humans. So which vaccines are most promising and what obstacles lie ahead?

Some of the vaccines in development rely on science familiar to anyone with an elementary understanding of biology– researchers inject the subject with a weaker version of the virus, thus triggering an immune response. But some of the most promising vaccines currently in clinical trials rely on methods entirely novel for human vaccine development.

Two of the five vaccines being tested are genetically engineered, referred to as RNA and DNA vaccines, and they would be the first of their kind. They involve injecting the subject with a sequence of genetic code which instructs the human cells to produce a specific protein. That protein is what causes the desired immune response.

The reason these vaccines are so promising is that they are in theory easier to manufacture, requiring only a relatively simple sequence of RNA or DNA and forgoing the complexity of dealing directly with the virus.  This is important because manufacturing and distributing the vaccine at the scale required by the pandemic might be an even greater challenge than developing the vaccine itself, says Dr. Paul Wilson, an expert on vaccine development and professor of global health policy at Columbia University’s Mailman School of Public Health.

NY City Lens recently spoke to Dr. Wilson about the convoluted process of developing a vaccine, the risks involved, who stands to profit from it and who gets the vaccine first once one is finally developed.

How does the effort to find a coronavirus vaccine compare in terms of scale and funding to previous efforts to find other vaccines?

It’s pretty unusual. I would say that, at this stage in the game, probably the money is almost unlimited in the sense that these are not the most expensive stages of vaccine development. When we get to the later stages where they’re trying to do large clinical trials, then there will have to be a prioritization. They won’t all go into phase three trials because that would be wasteful and too expensive. But right now, I would say that the amount of effort is pretty unprecedented.

Where is this money coming from? Is it mostly the private sector or do non-profit entities and the public sector have an important role to play?

The way that vaccines are generally developed nowadays is that there’s often important work that happens at universities. And then there’s work that happens at biotech companies. Sometimes those are working hand in hand because the people at the universities already have arrangements with a biotech. And that’s how the first stage has happened. But then the later stages of vaccine development where you’re actually doing the big trials and bringing something to market that usually happens at one of a much smaller number of big companies, because that expertise, especially the expertise in developing process to manufacture the thing at large scale is quite restricted. There are really only a few companies that know how to do that. And so the private sector is essential.

Is this also unprecedented in terms of the speed in which these vaccines are being developed?

I think so. We’ll have to wait and see how long it really takes to get to the end of this. People are certainly throwing themselves into the first stage, which is developing the candidate vaccine. That already involves a lot of things. You have to have isolated the virus, and you have to know its genetic sequence. The Chinese did that very fast. And then everybody was free to start working on these candidates. But ideally, you do a lot of optimization [the process of perfecting the vaccine]. You do a lot of animal testing. And we don’t know how much of that is really being done. It’s a balance between being able to do things faster and also taking shortcuts. But then we get into the clinical trial stage and my understanding is that as of now there are a few vaccines that are actually in trials and that there will soon be many more. There’s a long series of trials and I think it remains to be seen how much that can be sped up. So I think this early stage has gone really fast. From identifying the virus, to having something that’s in clinical trials in just two or three months, that is indeed very fast.

What’s in it for the private sector? Do companies stand to profit?

I think the profit situation here is murky, because obviously, if we had a vaccine now the market would be enormous because practically the whole world would want it. But it’s less clear that that’s going to be the case a year from now. So I think there’s some real risk. Nobody really knows how big the market will be. But there are other reasons why the private sector gets involved. It’s an opportunity for them to demonstrate that their technologies work. So, for example, the company that was the first one to go into trials, this company called Moderna, they have a very new technology. We’ve never had an RNA vaccine licensed. So for them, this is an opportunity to get government money to help them prove that a technology works. And that would then bring a lot more investment to them, which they could use, for example, to make a cancer vaccine, something which they think would be really profitable. So for biotechs, it’s an opportunity to demonstrate technologies, even if they don’t think this particular vaccine will be profitable.

The big companies like GlaxoSmithKline or Johnson & Johnson have a different set of motivations, where they have to worry about public perception. And so they may think there’s profit, but they may also be doing it because they want to appear to be do-gooders that save the world, because that’s good for their reputation. They’re also afraid of being criticized if they don’t get involved. So, PR issues are important for the big companies. For the small companies. I think it’s more about technology demonstration.

Wouldn’t there be a backlash if companies were perceived to be profiting from the pandemic?

Yeah, I think that’s also a very delicate game for the big companies. They probably see some opportunity for profit here. But they also know that they might not be able to fully exploit that, because of those concerns. There’s the concern that even though the United States would definitely buy the vaccine, and I think would give them a reasonable profit, they have to be careful not to be seen to be profiting excessively. But then there’s also the fact that the whole world is going to need this vaccine. And they’re going to come under pressure from Oxfam, and from WHO and so on to make the vaccine available at a much lower price in poorer countries.

What are some of the more promising efforts to develop a vaccine right now?

I think certainly the RNA vaccine. One of the other advantages of an RNA vaccine, if it worked, is that you could probably produce it in large quantities very fast. So I think that has to be on everybody’s list. And then I would also look maybe at some of the more traditional efforts by big companies. I know J &J [Johnson & Johnson] has a collaboration with a US Agency BARDA [Biomedical Advanced Research and Development Authority]. The reason those efforts are interesting is that those are companies that would know how to manufacture and scale up fast if their efforts were successful. I worry about some of these vaccines that might look good on paper, by little biotech companies or by universities, because I’m worried that there would be huge delays, even if their vaccines worked, because they wouldn’t be able to manufacture it.

There is immense pressure to develop a vaccine quickly. Is there a risk that researchers and regulators will cut corners?

I think it is a concern. And I’m less worried about it for vaccines than I am for drugs right now. Because I feel like in drugs, you can already see the corner cutting happening. And of course, our president is playing a big role in that. I think there’s very little chance that anybody is going to roll out a vaccine without a randomized control trial. And that is the gold standard. But of course, there are lots of other ways that we could cut corners for sure. I mean, we could accept the results of a much smaller trial, or we could accept results of more ambiguous trials. The other thing is that sometimes there are side effects that don’t show up until months or years later. And I think that we’re probably going to just have to take some chances. Certainly when it comes to things that don’t turn out for years later, we just have to make sure that you try to monitor later and hope that if those things showed up that you can get the vaccine off the market. Some risks are legitimate and some are not.

Some big companies like Pfizer are already building the infrastructure to manufacture the vaccine even though one hasn’t been developed yet. Bill Gates is doing the same thing. Can you explain why this frontloading is important?

You can have something which you can make in the lab, but to develop the manufacturing process, where you can have a huge factory, turning it out for millions of people, and having that meet the standards of the regulatory authorities, that’s very difficult. And that’s something that only these few big companies can do. That’s something we have to worry about. that they could have a vaccine that even looks that it might be working in trials, but it could take months and months and months to build and scale up the factories and develop a process that really works at that very large scale. That’s a potential big bottleneck here.

Gates is investing a lot in trying to line up manufacturing capacity ahead of time. If you’re going to try to get a company in India to reserve or build factory space for this, you’re going to have to pay them a lot of money, which they’re going to keep even if you don’t ever make the vaccine. It’s a big investment that you might have to make. And I think it’s a good investment in this case. But to really do that, you have to know what type of vaccine it’s going to be. You could reserve some factory space and maybe some aspects of the machinery, but parts of that are going to be very different if you’re making an RNA vaccine and if you’re making a live attenuated virus vaccine, so I don’t know whether Pfizer is doing that with a particular candidate in mind, or whether they’re thinking about this in general terms. But I do think we do need to do that if we’re going to not have that be a bottleneck later. Especially because we’re going to want to make this potentially available in almost unprecedented quantities and because we’re going to be trying to roll this out worldwide, potentially at the same time, which has never been done for any vaccine. Usually vaccines get rolled out in the US or the US and Europe and then if developing countries are lucky, they’ll get them five years later, sometimes 20 years later.

Once a vaccine is developed, who gets it first?

This is a huge issue. It’d be nice to think there was a system but there isn’t. Total Wild West. Total Hobbesian universe. This is where it actually matters physically where the factory is and I can’t believe I’m saying this. There’s a terrible fear that national governments in the site of production, or where the company is based, will try to require the company to supply to them first. There are people out there trying to come up with nice ethical schemes but all that will be out the window if the epidemic is still raging and we have a vaccine. It’s a terrible situation. What you hope happens is that the company which is developing it puts in place, for example, licensing agreements with companies elsewhere. Let’s say Pfizer, if they are developing a vaccine, and they’re based here in the US, that they could be pressured into licensing companies in India and China to make this vaccine. And those companies might also be under pressure to produce for India and China first. But for example, some of the Indian companies like Serum Institute of India, they have the capacity to produce for the whole world.

So two large companies in different parts of the world would have to band together in order to manufacture the vaccine at the necessary scale?

Yeah, I mean, that’s the hope right? And what form this banding together would take requires a lot of work because normally, first of all, there are patents. And so the companies would be, in normal circumstances, very reluctant to license their intellectual property to companies elsewhere, especially in potentially lucrative markets like China or Europe. The other problem with a vaccine is that it’s not like a drug. If you give an Indian company access to the chemical formula of the drug and a patent, they can make it because they’re very good at that. With vaccines, it can be more complicated because manufacturing a vaccine at scale is challenging. And it’s not just patents. It’s a lot of what we call know-how, things that the people who are actually designing this process have figured out. And so in order for the company in India to make the vaccine, they would need a license for the patent, but they would also probably need people from Pfizer to go over there and show them and that’s slow and it’s difficult and Pfizer might be very reluctant because that is a lot of their equity. It’s that know-how that they built over decades that only a few companies in the world have. If they give that to Serum, for example, Serum could use that in the future to make other vaccines to compete against them. So how much companies are going to be willing to give that up? We’ll see. But there will be a lot of public pressure, of course. So you would hope.

 

 

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