A Q&A with Gavi’s Seth Berkley on vaccines, Covid, and challenges ahead

Seth Berkley, the soon-to-be former CEO of Gavi, the Vaccine Alliance, apologized for being a few minutes late jumping on a Zoom call.

Berkley — one of the highest-profile proponents of vaccination on the planet — was under a denial-of-service attack. It was not his first, likely the handiwork of people who object to Gavi’s efforts to help lower-income countries purchase vaccines at affordable prices. “It is not fun when it happens, but it happens from time to time. I usually can tell because I get locked out of my email,” he said matter-of-factly.

Berkley has headed the Geneva-based organization for the past dozen years, overseeing an ambitious expansion of the number of vaccines Gavi helps countries purchase, and the number of doses delivered globally with its assistance. Originally set up to ensure children the world over had access to seven essential vaccines, it now supports purchase of 19 vaccines, including the enormously effective human papillomavirus vaccine (HPV), and helps maintain a stockpile of Ebola Zaire vaccine doses.

Kate O’Brien, director of the World Health Organization’s department of immunization, vaccines, and biologicals, calls Gavi “maybe the most successful program of supporting low-income countries for essential public health tools.” Gavi’s estimate of the number of deaths averted by its vaccines jumped from 4.5 million in its first decade of operation to 11.8 million over the past 12 years — the period of Berkley’s leadership.

“You kind of have to point to Seth in his personal capacity as the CEO… as having led the secretariat of the alliance through a very successful period, with increasing the breadth of protection that kids and adolescents have access to because of the vaccine introductions and because of scale-up of performance of the immunization programs to deliver those vaccines to anybody anywhere in the countries where children exist,” O’Brien said in an interview.

As he gets ready to leave Gavi, Berkley is both proud of many of the alliance’s accomplishments and a bit frustrated by the speed at which progress unspools in the international immunization sphere at times. He also wishes critics would acknowledge not just the failings of COVAX — the international collaboration set up to secure Covid-19 vaccine doses for countries that couldn’t buy their way to the front of vaccine queues — but also the astonishing amounts of vaccine it helped those countries obtain. In the 92 countries eligible to buy Covid vaccines through COVAX, an average of 55% of people have had a primary series of Covid vaccines. By the time the 2009 H1N1 flu pandemic — the last pandemic pre-Covid — was declared over, the corresponding figure was effectively nil. “I mean, this is an amazing accomplishment,” Berkley said.

STAT spoke to Berkley about his tenure over two recent Zoom calls. The conversations have been edited for length and clarity.

When do you finish at Gavi?

August 2nd. And August 3rd, I go on vacation.

What’s next for you?

My son has two more years in high school. I think right now I’m going to try and stay in Geneva to allow him to finish high school. And what I’m looking at doing is a series of things around these areas — new technologies, vaccines, some venture capital activities. As an adviser and a consultant to people in these adjacent spaces.

I cannot get over what happened in the pandemic in terms of the number of doses of vaccine that got delivered and the fact that they weren’t all delivered in upper-income countries. It was inequitable, certainly. But it was just far better than anybody anticipated, and I think we just write that off.

Obviously I’m a little defensive about this. But the idea that [some people] say COVAX was a complete failure — it isn’t. It wasn’t. And a lot of the things that happened, of course, were outside of our control, and those are things that can be mitigated in the future by creating different systems and ways of working. And there were some things that just didn’t work, and we need to be honest about that as well.

So let’s learn from the lessons, and let’s improve going forward, so the next time we do even better.

I should know this but I don’t. What is happening with COVAX?

The plan right now is this year we are integrating the COVAX teams and the COVAX work into Gavi. But we’re basically responding to countries’ needs and what they want per their own coverage. What is your national goal? And how do we help you get there? And we’re, of course, encouraging countries to vaccinate the high-risk population. And then we will put Covid-19 into the vaccine investment strategy, and we will look at whether over the longer term it makes sense to have a full program, a partial program, a stockpile or whatever, because, of course, we’re still trying to figure out what’s going to happen with Covid vaccination. What is the epidemiology going to look like? Are we going to have more variants? Are we going to have more outbreaks?

At a recent Food and Drug Administration advisory committee meeting, it was clear some of the experts felt it was questionable whether the general population is going to need annual Covid vaccines in future. Could the Covid vaccine market crater in the next couple of years?

I think the general assumption on the street is going to be that we probably will have another round of boosters. And so it hasn’t gone to zero. But if we do not have new big outbreaks, changing disease patterns, etc., it may be that people will not continue to get annual shots.

Now that would change if we had a pan-coronavirus vaccine, or we had a vaccine that prevented infection in addition to disease, because then you would argue that it might make sense to get that vaccine to try to keep yourself from having the long-term effects of many different Covid infections. I think the science is still unclear.

And lastly, everybody’s hot to trot on mRNA vaccines, but we haven’t had the side-by-side comparisons on duration of protection between adjuvanted proteins, viral vectored, and mRNA vaccines. And it may be that you get better long-term protection, cellular immunity protection, in other vaccines. But we haven’t had that data.

Moderna and Pfizer are not going to cooperate with those studies.

Exactly.

We are starting to see that companies are having trouble developing flu vaccines using the mRNA platform. Moderna has had issues. Sanofi has had issues. I think coming out of the pandemic there’s a risk that everyone thinks the answer is always going to be mRNA.

And right now it’s not. I have trust in science that they will get better at solving mRNA problems. But it may be that for some antigens mRNA may not be the best avenue.

If you can put yourself back to what you were thinking when you started at Gavi, how have things played out in terms of what you wanted to do at the organization’s helm?

I helped to get Gavi started when I was at the Rockefeller Foundation. … I’ve watched the organization from the beginning. It started out as a very small secretariat. And the idea was to try to move forward on new vaccines and to expand coverage. And what we’ve seen is extraordinary. We just announced in the midterm review that Gavi has vaccinated more than a billion individual children. And just to put that in perspective, that’s half of the world’s children every year. Right now an eighth of humanity has received a Gavi vaccine.

I’m very proud of the work that was done around Ebola, for example, where we were stuck in this situation where there was [an investigational] vaccine, but there was no real incentive to produce it, because it was a disease of poor countries, and the outbreaks were little. And we set up that advance purchase commitment, and we made sure that there would be doses available in the interim between having a product shown to be efficacious and when it was going to be licensed. We had a number of outbreaks and those 300,000 doses that were there were used. Today we have a licensed stockpile.

It’s a scary, terrible disease, but we’re unlikely to have a West African-type outbreak now, because of that stockpile.

Is there wood around you? Would you please knock on some?

Yes, right in front of me.

But I also think we got it wrong [previously] on the Ebola Sudan and Marburg vaccines.

Please explain.

The idea is that [with these vaccines for rare diseases] we should try to take candidate vaccines as far forward as you could so that if there was an outbreak, you could get them tested and understand whether they worked or not.

What I meant by getting it wrong about Ebola Sudan and Marburg is that with both of those, there had been some vaccine work done, but the candidate vaccines weren’t in vials ready to go when epidemics occurred. So what we did is we began to have a discussion about what an end-to-end process would look like for that. And there were two parts to the process. One is having those products available and ready to use for clinical trials. And then the second part is, if those clinical trials show promise and you’re in trouble, do you have enough doses to use beyond the clinical trial in a compassionate access-type approach? Because if you remember, four years after the Ebola Zaire vaccine was shown to be 100% efficacious in the field trial in Guinea, it wasn’t yet licensed.

So we asked the board to create a virtual pooled inventory for two specific conditions — Ebola Sudan and Marburg. It’s not really a stockpile, because we tend to talk about stockpiles of licensed products. The idea is this would be an investigational vaccine that was stored. Now in this case, we knew that a number of the partners developing these vaccines had already made doses to use in Phase 1 clinical trials. So we didn’t need to worry about that. But if there is a need for us to invest in larger amounts of this for use in an emergency, we have permission to do that.

But the really important point was to come back to the board in December of this year for a broader strategic plan on how that whole effort would go, not just for those two diseases, but for Lassa fever, Crimean Congo hemorrhagic fever, etc. A lot of work has to happen.

If you could get a do-over for your time at Gavi, is there anything you would do differently?

Many things. On the routine vaccination side, when we started doing HPV, there was a lot of angst about this being a different age group, and different concerns. And so we ended up doing a set of pilot programs. I think we probably could have ended those pilot programs quicker, and we could have moved right into vaccination. This is our most impactful vaccine. There are more women who die of cervical cancer than who die in childbirth today, so we need to get that vaccine out.

I could make an argument that on the malaria vaccine, maybe we didn’t need to have that long implementation pilot. That was not something that we decided. But you know that vaccine, moving it quicker would have saved lives.

In Covid, I made a mistake — and I will live with that. We normally bundle delivery and vaccines together, and we were under enormous pressure. There was so much money flowing, there were big institutions who had massive amounts of money in this area. And therefore, we felt, OK, we don’t need to worry at the beginning about delivery, because others will flood countries with money to deal with that. That turned out not to be true. And at the end we had to put a delivery program together. And it occurred later.

As you look to the future, what worries you about this sphere?

A few things. We’re going into a very tough economic time. And I know it’s going to be difficult to raise resources. The world tends to think about things seriatim. In Covid, that’s the only thing on the agenda. Now we’re in the Ukraine war. That is important. I’m not balancing the importance of different things. But we need to think about this and this and this.

I think we’re going into an era of poly-epidemics. Look at what’s happening with land use and population growth and climate change and climate crises and floodings. We’re going to have more contact with humans and animals and all these things. So I think we’re going to see more and more outbreaks. And the challenge there is, how do we make sure that we continue to prepare countries to have resilient systems? And how do we make sure that we have vaccines ready to go, and that we continue to look to use the most powerful preventive mechanisms for infectious disease? How do we make sure that gets to the people who need it most?

One of the results of the pandemic is that vaccine resistance, hesitancy, and rejection have increased. It feels like the anti-vaccine segment of the population has expanded and hardened — and has metastasized to other parts of the world.

We always worry about that. Vaccine hesitancy has existed since the first smallpox vaccine. But the truth is, what changed here was really two things. The politicization of vaccines. That was really bad. And the second thing is the social media echo chamber and the ability of people to nefariously use these systems to spread misinformation. And for me, those are really big problems.

Another thing that has come out of Covid is the push to develop regional vaccine production capacity. I get that completely. But how do you do it? Vaccine manufacturing facilities have to be used on an ongoing basis, and have to be maintained.

That is the secret.

How do we get to the place where you can keep regional vaccine production capacity warm?

After Covid there was this real push for African vaccine manufacturing. There are now over 30 different projects going on. And one of the challenges is, there are 30 projects that started out as being Covid vaccine projects. And we don’t need 30 new Covid manufacturing facilities. We probably don’t need one.

So Gavi did get involved. We have a program now to work on trying to help countries create the possibility of sustainable vaccine manufacturing facilities. And it includes helping them understand what the state of the market is — the vaccines for which we have too many producers, and those we don’t have enough of. Helping to build firm demand. That will be important. And we’re looking at creating an advance market commitment, which would be used if a new manufacturer is able to bid on a competitive tender for a Gavi vaccine. The idea would be that we would provide a payment to them for the difference in cost between what a well-established, sustained manufacturer would be [charging] and their startup cost.

It’s going to cost more.

There’s been some discussion about the future of Gavi, with some people saying Gavi’s job should be to put itself out of business by 2030. Thoughts?

We actually had an active conversation on whether we should go out of business. Because remember, the original idea is that countries would graduate from Gavi, and then maybe there’d be no need for it anymore. It turns out that some of the poorest countries are going to be poor well beyond 2030. So it’s maybe not a short-term goal, but that conversation is worth having.

But the other side of that is: Who will help with new vaccines for new agents and new technologies that may make a difference? And as we move into an era where we’re getting lots of new technologies, new vaccines, new ways of creating biologics, I think Gavi will have a role to play, although a different role than we played in the past.

There was recent work reported on needle-free vaccine delivery. A patch. Talk to me about the potential of that.

It’s very exciting. It’s moving way too slow for my taste. We’ve been working on patch technologies for 15, 20 years, 30 years. The real advantage of it is, you don’t need a health worker. And you can use it outside of health centers. You can even self-administer it. And my hope is it gets approved as soon as possible.

It’s particularly transformational if you think about something like the hepatitis B birth dose. The problem is: How do you give vaccines to newborns who are born outside of health facilities? That’s a real challenge, because hepatitis B has to be given quickly after birth. So this is where patch technology would be transformational. There are real advantages of these tools, and the challenge is going to be how to push that forward and get those approved. Right now the timelines are longer than I think they should be.

What are the timelines?

I’m hearing people talk about three, four, five years to get approval.

In our conversations, there have been so many times where you’ve said “This didn’t move fast enough for me.” Are you an impatient person?

I am impatient. I’m impatient when it has to do with people’s lives.