Finding a global solution for a global problem

In the pages of IAVI Report, and countless other places around the globe, Seth Berkley doesn’t require an introduction.

The founder and former president and CEO of IAVI is a visionary who has spent much of his career promoting the development of new vaccines and implementing immunization programs that benefit the world’s poorest people. Since leaving IAVI in 2011, Berkley has led Gavi’s largest expansion, which has resulted in the immunization of an additional 300 million of the poorest children across the globe, preventing five to six million deaths in the process. He is relentless in his commitment to public health and travels almost non-stop, at least he used to pre-COVID. Like all of us, he is spending much more time at home these days.

Since its inception in 2000, Gavi has facilitated the immunization of more than 760 million children worldwide, averting a staggering 13 million deaths from vaccine-preventable diseases. Nearly 90 percent of the world’s children now receive at least one round of childhood vaccines, almost half of them as a result of Gavi-supported immunization programs. They aren’t stopping until they reach them all.

That mission has become even more complicated in light of the ongoing COVID-19 pandemic. As airports and countries around the world shut down in an effort to limit the spread of SARS-CoV-2, public health programs, including Gavi-supported immunization programs, faced multiple setbacks. This hasn’t yet resulted in widespread outbreaks of vaccine-preventable infectious diseases, but it is still too soon to judge the widespread impact of this pandemic. At the virtual COVID-19 Conference held July 10-11 in conjunction with the International AIDS Society’s conference, Bill Gates warned of another consequence—the disruption in HIV/AIDS treatment programs that could prevent people from receiving life-saving antiretroviral therapy.

Amidst all of this, Berkley’s commitment is unwavering. In June, with the world in the throes of the pandemic, the U.K. hosted the Global Vaccine Summit, an effort to replenish Gavi’s financing through commitments from world leaders. It was overwhelmingly successful—31 donor governments, and eight foundations, corporations, and organizations pledged more than US$8.8 billion to Gavi, exceeding the replenishment target.

In addition to ensuring that 100 percent of the world’s children receive at least one round of routine immunizations, Gavi, along with the Coalition for Epidemic Preparedness Innovations (CEPI) and the World Health Organization, is now also helping coordinate the development, manufacturing, and eventual access to COVID-19 vaccines through the COVAX facility (see COVAX: Facilitating global vaccine access). The goal of the facility is to accelerate the development and manufacturing of COVID-19 vaccines and to distribute them globally to the individuals at highest risk in an effort to halt the pandemic as quickly as possible. It will allow even the poorest countries to access vaccines. The idea of distributing vaccine doses equitably based on need and not the ability to pay is one of Gavi’s core missions. “Unless everyone is protected, we are all at risk,” Berkley said.

I spoke recently with him to discuss the COVID vaccine pipeline, the COVAX facility, Gavi’s focus after the replenishment, and his hopes and fears during this pandemic. An edited version of our conversation appears below.

Are you optimistic about the prospects for COVID-19 vaccine development?

Yes and no. If it turns out that the Spike protein on SARS-CoV-2 is the right target, then the fact that we have about 160 vaccines in development says to me that we have a pretty diverse and wide set of approaches, and so I think it is likely that some will work. But there is that caveat. If it turns out that the Spike protein isn’t the right antigen, then there are very few candidates that are not based on that.

The second point would be that we don’t know whether we will be able to get protection in all age groups, including the elderly, and we don’t know how long the protection will last. We also don’t know if this coronavirus is going to be like seasonal coronaviruses, and therefore, you can get re-infected, or if there will be long-term immunity, etc. There are a lot of other questions too, but in terms of getting immunologic protection from the vaccine, I’m optimistic assuming that Spike is the right target.

You seemed to be one of the first people to raise the issue of equitable access to an eventual vaccine. What steps is Gavi taking to ensure that vaccines, when available, are not just accessible to those countries who can afford to pay for them?

When the pandemic started, we thought about the need to have an advanced market commitment (AMC) for the Gavi countries, because as the poorest countries in the world they would not have the resources to be able to compete with other countries. Those are traditionally the countries we think about. But it became quite clear over time that there was a risk that even if there was adequate financing for Gavi countries, that given the intense global desire for a COVID-19 vaccine and the fact that in the first 18 months there is no way there is going to be excess vaccine, there was a good chance that even if a country had the money they could end up not being able to access a vaccine.

So that made us pivot and starting thinking about how we might supply vaccines globally to a subset of the population to try to control the pandemic, which from a public health point of view is the efficient way to do it, rather than taking a nationalistic approach to protecting just your own people. Obviously if a few countries buy 100 percent of the vaccine for their entire population, then in the early days there will be no vaccine for anybody else.

That pivot was important because it led to the design of the COVAX facility, which went beyond the AMC that we also launched. The idea of the COVAX facility was to try to create a place that other countries could self-finance vaccines as part of an overall portfolio. The idea is that if we can get enough countries interested, then we could scale up production adequately and make sure that there is a vaccine available for developed and developing countries.

So that covers all countries?

All countries. The idea is that low- and lower-middle-income countries fall into the AMC, which would be the normal Gavi mechanism. We are still debating whether to also include the 12 International Development Association-eligible small countries that are mostly small island states. Then the upper-middle income countries and high-income countries are eligible to procure the self-financed vaccine, hopefully with a tiered approach that would allow people to be able to afford vaccines.

Speaking of affordable vaccines, what are your thoughts about the price of an eventual COVID-19 vaccine?

We had to estimate prices in our models and for fundraising, but since we have no idea which vaccine is going to work—whether it is going to be one, two, or three doses, or what the manufacturing yield is going to be, etc.—it is impossible to come up with a price. We just used a weighted average price of $10 a dose as a proxy for about what it will cost.

Certainly, there are many approaches that are in the pipeline that would not be extraordinarily expensive to make, and then there are some that might be expensive to make, so we’ve been pragmatic. Not all manufacturers are the same. A big manufacturer might be able to say we can do this at cost, plus some minimal amount, rather than not for profit. But there are other groups that are small, venture-backed companies that frankly can’t say that. They would need to have some type of return, and then the challenge would be to structure a tiered price that would give the companies a return that would be appropriate—not excessive, but appropriate—and would do it in a way that was fair for all countries. We are trying to be pragmatic because of course we want access to whatever vaccines are worth having access to.

And how are you thinking about the manufacturing of vaccines?

We’re thinking about it from large companies, contract manufacturers, and from the developing countries vaccine manufacturers network, working closely with CEPI. CEPI is setting up relationships for particular approaches, but if those approaches were to fail, they are trying to be in a position to capture the manufacturing, or vials, or goods that are necessary to produce a vaccine and use them for another candidate. One of the challenges with vaccine nationalism is not only that you might have access to just a couple of vaccine approaches and those vaccines might not work, but also, if every country is going out and trying to produce their own vaccines and many of them are going to fail, then you can end up in a situation where you use up all of the manufacturing resources. And then when you have a successful vaccine or vaccines that are the ones that should be scaled up for everybody, there won’t be enough facilities or the products you need to make those vaccines successfully. That would obviously be a tragedy.

Do you think that there is an appropriate balance in the vaccine pipeline between candidates that are quick to develop and those that are more likely to succeed?

Well, there are two critical truths here. One is that we need vaccines quickly because of the state of the global pandemic. The second is that we also need vaccines that work and are usable. To do that, you want a full portfolio of vaccines. CEPI’s philosophy is to try to have different types of vaccines. Some are going to take longer to make; others like Moderna’s mRNA vaccine candidate, which was the leader in terms of speed, was being tested in humans in 63 days. But there are also no licensed mRNA products, and with these new approaches there are concerns about what the regulatory pathway will be and the process of scaling up manufacturing to produce large volumes.

The question, in a sense, is are we talking about the tortoise or the hare here because you don’t want to exclude either from the race. That is why it is important to still focus on products that are going to take longer to do the bioengineering for in the beginning—like a live-attenuated vaccine or live-vectored approaches. We need to make sure that we’re paying attention to the full range of approaches. What may end up happening is that we will have a first phase of vaccines that will be used acutely to try to control the pandemic, and then these will be followed by a second phase of vaccines that might be easier to use, more immunogenic, work better in the elderly, or be single dose rather than multi-dose.

You’ve spent so much of your life trying to convince the world to focus on vaccines and now everyone is talking about vaccines!

Except for the people who are talking about how they would never take a COVID vaccine.

Well there is that issue too. Why do you think there is still so much vaccine skepticism?

It’s interesting. I have no answer for this. I think that there is fear out there. But my assumption is that when you have a vaccine that works and people start using it, and those people are being followed and it is shown to be safe, and those people are then able to resume a normal life, I have to hope that this will flip and substantial numbers of people who are nervous now become less reticent to be vaccinated.

There is always a small group who are never going to take vaccines, then there are those people who love and trust vaccines and will take them, and then there’s that group in the middle. What we’re looking at is the group in the middle. You want to make sure you move those people toward wanting vaccines and not in the other direction.

How has COVID-19 affected the implementation of Gavi-supported immunization programs? Have you seen a spike in vaccine-preventable diseases because of COVID-related interruptions?

Yes. We don’t know the full extent of the interruptions yet, but the numbers are quite dramatic—73 percent of countries have had outreach impacted and 63 percent of countries have had a moderate impact on routine vaccinations. Of course, we don’t have real-time monitoring everywhere, so we can’t give up-to-the-minute statistics, but clearly it has had a big effect.

The hope is that there was a dip and that now those numbers will come back up again as people get used to the situation. But the immunization rates may not go up quite as high because people may be holding their families back, and you also may have a slower process with people using PPE [personal protective equipment] etc. The hope is that we can keep population immunity at a high enough level that we don’t have outbreaks. But we’ve already seen a range of outbreaks occur so far. We haven’t yet seen massive full-country outbreaks, but if you think about it, it’s only been about three months of reduced uptake, and so it is still early days. One of the questions is whether we will be able to do catch-up campaigns in the near future, or is this interruption going to last for a substantial period, in which case we would have to worry.

Just in terms of the supply chain, we had a period where airports were shut down and we were worried about stock outs all over the place. Now we’re almost back to the same shipment levels as before the pandemic began and we are catching up on back-up shipments.

And in the midst of all this you held the Global Vaccine Summit, which was a resounding success. What are Gavi’s priorities coming out of the summit?

Well, the core of the replenishment was laid out pre-COVID and it really had a few major points of focus.

We’ve made it to the point where 90 percent of children receive at least one dose of routine immunizations, and that’s extraordinary. Now the focus is on that last 10 percent, the so-called zero-dose children, two-thirds of whose families live below the poverty line. Those families live in places where there are no health services at all, so if the children get sick, they are more likely to die. And if an epidemic starts there, it is more likely to spread. The radical idea was to reach that last 10 percent or get as close as possible to universal access between now and the end of the Sustainable Development Goals in 2030.

Image courtesy of Gavi

But these vaccines don’t deliver themselves, so in order to do that you have to build a health system for that last mile. This has many positive effects because those are the areas with the highest mortality rates. So the core of Gavi 5.0 is built around this idea of going not just nationally, but sub-nationally, working with countries to focus on using local data to identify where the clusters of zero-dose children are and to really begin to have indicators that look at how many of them you’ve reached, and in the process leave behind health systems that extend beyond vaccines. That’s the plan. Now, of course, we are starting with many more zero-dose children and many more under-immunized children as a result of COVID, so the first question is, how long will it take for us to get back to baseline? But the core strategy stays the same.

Ironically, the other part of the strategy was to strengthen our work around epidemics and to have better stockpiles and surveillance so that we are better prepared to deal with global health emergencies, which we know are evolutionarily certain to occur. The idea was that given global warming, increased urbanization, and increased population density, we are going to see more outbreaks that we need to be prepared for. And I think that will obviously be important going forward.

The additional financing we received is quite important because we had cut back on some of our previous ambitions when we added inactivated polio vaccine into the core of Gavi. As a result, we cut about $600 million out of our health systems financing effort. This new round of funding is going to allow us to get back to full financing and really try to drive things forward. We haven’t fully decided what the additional money will be used for, but a substantial portion will be on this sub-national effort to go the last mile and reach the zero-dose children.

These are strange times. What keeps you up at night?

I used to worry about the replenishment and securing funding in the time of COVID. But now, to be honest, what keeps me up at night is that we’re at a tipping point. This is a global pandemic that started from a small outbreak in Wuhan, China, and spread to 180 countries in three months and we are now seeing this kind of nationalism occurring. It is certainly possible that a nationalistic approach could result in a dozen or two dozen countries buying up all the doses of vaccine, leaving none left for the rest of the world. This is not a great idea, not just from an equity point of view or a humanitarian point of view, but also from a public health point of view. If you have massive outbreaks of virus circulating, adapting to humans, mutating, and then spreading, you’re never going to solve this. I worry about a world where governments are focusing on vaccinating every person in their own country, and everywhere else people are dying. I hope we can get back to understanding the importance of trying to solve this problem for everyone. It is a global problem that needs a global solution.