Coordinated Global Effort for Effective COVID-19 Vaccine

EVN Report: You’ve called for a coordinated global effort – scientists, private companies, governments, all coming together to get further, faster in the development of a vaccine. How likely do you think it is that that will happen? And what are going to be the biggest hurdles?

Seth Berkley: I think that that would be the rational response, because science is global and you don’t yet know, which product is the best, what adjuvants you’re going to need, what other things are going to have to happen, so in an ideal world, that’s the way the world works in a rational way. Of course, I can’t predict what’s going to happen. There are people wanting to push their own science or hold things to themselves and I think that’s not the best way forward. So for me I’m hoping that there will be that type of open process but I can’t guarantee it.

EVN Report: Efforts are underway for other solutions, like drugs that can be effective against this coronavirus. Do you expect those will emerge more quickly than the vaccine? How do those two timetables generally work?

SB: It’s hard to predict because we don’t know yet fully about the infection, the organism causing the infection. It is likely that you’ll have a faster timetable with drugs. [They’re] much easier to use, you can test them right away on the people who are sick and are critically sick. So there are no ethical issues associated with that. With the vaccine you have to understand what the correlates of that immunity would be, whether the vaccine can produce that, whether it works in all different age groups.

And of course, as a product you give to healthy people the concerns for having it be completely safe is even higher than it would be for drugs you’d use for somebody who is critically ill. So normally the timelines are much faster for drugs than the vaccines, but of course it depends upon whether one can develop drugs that work against this virus.

EVN Report: Are you encouraged by what you’re seeing so far, in terms of drug tests?

SB: I don’t follow drug development as well as I follow vaccine development, but I do see that there is an attempt to not only test a lot of different products, a lot of companies have put their antiviral libraries up there. There’s been a lot of discussion about non-specific things that might have some effect here. And I also see some evidence of randomized controlled clinical trials underway or getting started against these different agents. So I’m optimistic that we’ll at least get scientifically-based answers soon.

EVN Report: As you’ve put it, there will always be a period of time when we’ll have an exciting vaccine and not enough doses to go around and that’s going to mean making hard decisions about who should get it. Is there some protocol or formula out there today that addresses that question, or are we really seeing this figured out in real time?

SB: It is going to be figured out in real-time. And why is that? There is a protocol that says if we have products that save lives, we should try and make them available globally. That’s what Gavi does. It was set up to do that, to make sure that these exciting new vaccines could be made available to developing countries and eventually could be manufactured at the scale to make them available to everybody. So there are protocols to do that in general.

But in this particular case, it’ll be a number of competing activities that will occur at that moment in time that we have evidence of the product. So first of all, you’re probably going to want to protect your healthcare workers, because they obviously are at the front lines and they are also the people who not only, if they are infected, can’t help other people, but also they can transmit an infection. You’re also going to want to focus on those at the highest risk, that includes probably the elderly, in this case, or people who have comorbidities, that are particularly likely to cause problems with this disease.

So if one is trying to deal with those groups, you need to have protocols and ways to get that, and then third, you want to pay attention obviously to places that have epidemics out of control, because you don’t want that happening.

And the last one, of course, is that this may be a vaccine that every person in the world wants. Depending upon how the epidemiology is, as we understand better who’s getting infected and when they are transmissible. So there is going to have to be not only a geographic discussion, but also a discussion on public health significance of the different groups and therefore how that should be prioritized. I suspect the normative guidance will come from WHO, but there will also be obviously country-based guidance as well and that will all need to be coordinated.

EVN Report: The way things work now, if there were to be a great success in developing the vaccine tomorrow, what kinds of hurdles or disadvantages would small countries face in terms of access? How much harder do they have to try, how much longer might they have to wait for their own stockpile?

SB: Well, of course, one of the goals would be to deal with this ahead of time and try to make sure that countries would have access based upon what their need is and not based upon their size or their potential financial might. But of course, that is a difficult situation to get to and something that I think we would need to work on. Certainly today…we [at Gavi] deal with the emergency stockpiles of vaccines for epidemics. So we fund stockpiles for cholera, yellow fever, meningitis and now Ebola as well [and distribute] based upon need. Countries apply and they get a decision based upon the need for those outbreaks, not based upon whether they’re rich or poor. If they’re Gavi eligible countries, we pay for the vaccine and we pay to distribute it. If they’re non-Gavi eligible countries, we give it to them immediately, but they have to pay us back and we let them pay for its distribution. That is a global mechanism that is out there to try to make sure that these vaccines are available to those who need it.

EVN Report: So currently it’s about financing mechanisms to help those countries compete at market rates? For the same vaccine, is that a correct description?

SB: Not really, because what we do is we come up with a stockpile that is based upon what we expect to be the need for those products. Obviously, those products could be needed more because there’s an explosive outbreak. But so it’s an educated guess that is defined over time. Once that happens, everybody gets access to that stockpile at the same price we are able to buy those doses. So it’s not about a market issue. It’s about what we’re able to negotiate for those doses.

EVN Report: And “we,” in that sense is GAVI. So GAVI is purchasing that stockpile and then trying to make sure it gets to all the places that need the most.

SB: That’s right. And it’s for the whole world. I mean, obviously, you know, it is possible that if you had a big outbreak somewhere else, that a very wealthy country might go directly to the manufacturer and try to buy it up. But one of the reasons we try to have a stockpile like this is, you know, some of these companies for rare diseases just can’t scale up at any time. And we want to make sure there’s enough doses for what we expect would be the potential outbreaks wherever they are in the world.

EVN Report: So what we’re seeing now, what David Nabarro has called “a market failure for PPE,” for example. It’s really the Wild West [in access to medical protective gear] —  some of its market forces, some of it is purchasing power, some of it is logistics to certain countries. Is that sort of the worst scenario for what would happen with the vaccines that we’re trying to avoid?

SB: I mean, I think even worse than that scenario would be an intentional withholding and not making it available to people who needed it. But of course, that’s not the way it should be. And one of the challenges in any emergency, particularly early in the emergency, is that it’s hard to plan out and prepare. I have to say that it’s not like the world hasn’t been talking about this for a while. It’s not like we haven’t been crying wolf over and over again about the need to have adequate quantities of protection equipment, but also platforms for development of vaccines as well as, you know, distribution systems. And so we’re a lot better off than we were five years ago when the Ebola outbreak occurred. But clearly, the world is not where it should be.

EVN Report: So how do you want the process to be engineered? What are the ideas or solutions that are being thought through now about fair distribution — who gets the vaccine, how smaller and lower income countries fare? How would you like it to work?

SB: What I would like to see is an agreement that says there will be allocation without regard to the wealth of the country or size of the country. And it would be done on a set of different axes. The first would be on public health approach initially in the early days, because by definition there would be a limited amount of vaccine when it starts or where it is needed the most and who needs it the most. And that does require some judgment calls because, as I said, it may be health workers in one place and somewhere else it may be a country that has a particularly bad outbreak that cannot bring it under control. We don’t yet know what’s going to happen in the developing world, but obviously it’s much harder to do the same type of social isolation as the same type of personal hygiene and sanitation. If you don’t have running water, it’s very hard to hand wash all the time. And of course, if you’re working in the informal economy, it’s very hard to not work. So I think there are challenges in the developing world that are going to make it particularly bad there. So I think what we’ll need is a situation where that vaccine is made available, the early doses to where it’s needed the most. And then over time, as the production goes up, one needs to make sure that there will be equitable distribution to the full range of needs. And so it’s kind of a matrix of need-based distribution and then global fairness in that distribution. That would be the ideal way to do it.

EVN Report: And the WHO is where a conversation like this would sit, I take it? Does that mean you need to get consensus from every member country to play by the same rules?

SB: That is what you would like to do. But I think where you start before that is going to be in the financing for this. So as G-7, G-20 leaders and others come together to try to deal with this epidemic, my hope is that part of making these grand investments, they will include these access provisions. Initially, I believe personally that we should be talking about a global public good for a period of time until the epidemic is under control…what you’d want is tiered pricing in that circumstance so that you would have some fairness and access to make sure that everybody could afford it.

EVN Report: And how do you see that playing against or playing with the interests of private companies, some of whom might want to bank on this as a blockbuster for their own interests?

SB: Well, I think that’s why the conversation needs to happen now, because, you know, if there is to be public investment in trying to move this forward as quickly as possible and use of clinical testing sites and ultimately scale up and manufacturing sites, you know, against those investments, if companies want to engage with that, then there should be some requirements, some tit for tat that requires them to have some fair and equitable tiered pricing.

By the way, that is the most efficient way to make money, because if you follow Ramsey Pricing, which is the economic theory of this – in your highest market, you charge what you can with what the market will bear. But if you charge less in your middle income markets and just a little bit in your lowest income market, you’ve maximized the size of production which drives down the cost of goods, which means you maximize profit across the entire chain. So this is good for business if it is done in a pure well as well as good for society.

EVN Report: Over your career you’ve seen many developing countries go through many health crises. What are some of the best strategies you’ve seen or how would you turn that into advice for this moment as low and middle income countries try to manage the coronavirus outbreak?

SB: Well, I think the most important thing is to learn from what the rest of the world is doing…to learn from each other. Because although the strategies originally were done in China, because that’s where the epidemic began, some countries, as you know, didn’t listen and learn from that at all. Others did. And what’s really important for countries is that they need to learn from each other.

What is the best way to do this? For example, [look at] food distribution for people who are malnourished in a developing country to avoid large gatherings of people and everybody rushing in to try to grab it. What are the distribution channels you would use? How do we give advice to people in urban slums on what they can do? So I think it is important to follow the science. It’s the only way to go.

We won’t have perfect answers. And then we’re going to have to adapt that science for the local situation. For me, that’s an important lesson for poor countries. Don’t listen to false truths…but learn from what others are doing successfully. Look for the positive deviants that occur and try to follow that given the systems that you have.

EVN Report: Any case studies that stand out or scenarios that you’ve been through that you think should be looked at now by the low and middle income countries on how to manage this? Such things as handouts, food handouts, mitigating the financial losses of informal workers, anything that comes to mind?

SB: It’s hard for me to comment on that. That’s not my area of work. What I can comment about is public health aspects. And I think what we learned in Ebola, for example, was it was very difficult to have discussions on things like burials and on things that were quite culturally sensitive. And initially, you know, outsiders came in and said, you know what, here’s what you do. And they began to learn that you needed to follow the cultural sensitivity. You know, white body bags versus black body bags…having respectful engagement that allowed this part of the process. These are things that are really important…what you need to do is have those conversations. It isn’t always the fastest way to get there, but it’s the best way to get there. And ultimately it leads to a better result. And that leads to a better solution.

EVN Report: There seems to be science, or at least speculation, that there are multiple strains of coronavirus driving this pandemic. Do you have to manage vaccine development differently in that case?

SB: Viruses always mutate, so there will always be differences in strains and that’s how we can track viruses across some different populations as they move around. That does not mean that the immunologic determinants of protection are changing as the virus is changing. So something like measles, you know, we’ve had a vaccine for 50 years that still is effective. It still works. It works in a targeted area of the virus. There are other examples of where viruses are changing all the time and it affects the immune response. So it really depends upon the virus. My understanding so far is that although there have been changes, they are not dramatic changes. And it probably is not going to affect the part that would be the part that is being used for immunologic recognition. But given that we don’t know what the protective immune response is yet, I can’t say that definitively.

EVN Report: Is there anything else you wish we all knew and understood about the threat we’re facing?

SB: I think that the hardest question is really, will you get lifetime immunity to this virus, whether it be a natural infection or whether it be through vaccination? SARS gave very strong immune responses and those have seemed to have sustained over time. But of course, SARS has disappeared. So we don’t know if those people really are immune to something like this for the coronaviruses that occur as common cold viruses. Those viruses only give you protection for about 10 months to a year. And so you can get reinfected with the same strain. So understanding some of the basic biology is going to be very important to understand both what we need to do on vaccine development, but also what the long-term effects are going to be.

EVN Report: As someone who sees this all from a public health perspective, what do you tell someone who worries more for the economic fallout or businesses closing down? I mean, these are very difficult philosophical balances we’re being asked to consider in real time. How do you frame it? How do you see it?

SB: Well, I’m primarily a doctor and a public health worker. And life is sacred. And so the idea that you make a tradeoff is not a good one. Now, practically speaking, obviously, tradeoffs get made all the time. I think for this particular disease, the faster we get serious about controlling it, the faster we get it under control, the faster then the economies can come roaring back again.

The worst case scenario is either to do nothing and then let the disease get so severe that you have to deal with it in a much more severe case or to kind of do it half-hearted and then have both economic damage but also not get it under control. So it seems to me and I think Bill Gates has been very articulate on this, both in his TED talk and his CNN talk afterwards. It’s about trying to come in quickly, get that reproductive rate well below 1 as quickly as possible, and then make a decision on how we are able to restore things. But if we don’t do that, then we’ll be in the worst case scenario of having really severe outbreaks that may not be able to be easily controlled and overwhelm the health system.

EVN Report: In Ebola, as in other outbreaks, we saw a significant toll in terms of the deaths of doctors, nurses and healthcare workers.That would seem to put more strain on developing world health systems, in terms of their ability to be resilient to outlive this, in a sort of strength of the system capacity. Is there something particular we need to consider about protecting the doctors and nurses in the developing world, or frankly, building any sort of resilience into those systems?

SB: Well, absolutely. So, first thing about that is one of the tragedies is that it’s not that there were no PPEs around. There was PPE around. It was often hoarded by individuals, by companies, by the worried well. And so I think one of the critical issues is making sure that you get your health workers that equipment because they are on the frontlines and they are the ones that are being exposed. You’re actually right, in the early days [of the 2014-2016 Ebola outbreak], Sierra Leone lost almost 20 percent of their health workers. And this is a tragedy beyond belief. Of course, afterwards we’ve worked to try to re-train and rebuild the health system there. But what you want to do is avoid that as much as possible.

One of the things that’s important in any pandemic is you start out with a low knowledge base. And that’s why that learning is so critical. What are the techniques? How do you best learn to protect your health workers? So I think in a sense, the people who are at the frontlines are the heroes always in these circumstances. One of the questions that will be important in understanding the immune response is, are people who have had the disease, particularly mild disease, are they immune from the disease going forward? If they are, they can also become frontline health workers. That was done in Ebola, as you know, and it’s been done in other diseases as well as a way to, you know, help the process when one doesn’t have another choice. Of course, we don’t know that right now. And so it’s a challenge. But that is not a crazy strategy going forward. And that’s why having the test, gets understanding of the baseline of infection, how many people are infected. It’s important to understand all of this.

The challenge right now is, what we need is for everybody to embrace what is the best in humanity and not the worst. And I mean, this is if you go back and read The Plague [by Albert Camus], you know, this is exactly the point that he makes in that book. Fear can drive you in any one of two directions. But it’s by embracing humanity and doing the right things that we show our humanity. And that’s going to be critical in a situation like this. Both now, when it’s acutely bad, but even going forward, as we begin to see solutions in sight.

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