The past, present, and future of IAVI

With IAVI marking its 25th anniversary, it is a fitting moment to reflect on the organization’s history and its evolution. It also provides an opportunity to discuss how the organization is preparing to contribute to the effort to address the mounting public health challenges the world will face in the coming decades.

Today, vaccines are a topic of everyday conversation. Ever since the COVID-19 pandemic began its deadly sweep across the globe, the rapid development of and access to vaccines has been at the forefront of everyone’s minds.

When IAVI was founded 25 years ago, HIV/AIDS had been around for more than a decade and more than 20 million people, globally, were living with the virus. A million others had already died. Developing and expediting access to life-saving antiretroviral therapies was a global priority. Yet there was not a coordinated effort to develop an HIV vaccine.

IAVI sought to change that. And in doing so, this newly formed organization wanted to make resource-limited countries that were bearing the brunt of HIV/AIDS a central part of the development and testing of vaccines so that they would be among the first to benefit.

After 40 years of research, an HIV vaccine is still not within reach. This isn’t because of a lack of investment or effort. Rather, HIV remains one of those most formidable challenges scientists have ever faced. COVID-19 vaccine development may make it look easy — it isn’t. Still, efforts to understand and confront HIV are ongoing and progress is being made. At the same time, this work is helping accelerate other scientific pursuits. COVID vaccines shattered records with their speedy development, but it was the innovation and persistence of HIV researchers that laid some, if not much, of the groundwork for these products.

Today, innovation and a steadfast commitment to access remain at the heart of what IAVI is and what it does, not just for HIV, but for many other existing and emerging infectious diseases.

To discuss IAVI then and now, I recently sat down with two passionate and visionary IAVI leaders: Seth Berkley, IAVI’s founder and first president and CEO who is now leading Gavi, The Vaccine Alliance, where he is overseeing, among many other things, the global delivery of COVID-19 vaccines through the COVAX facility; and Mark Feinberg, IAVI’s current president and CEO, who helped advance the development and availability of several vaccines throughout his career in industry, academia, government, and the non-profit sectors.

These two leaders are ardent believers in the power of science to deliver transformative public health solutions. They also share an unwavering commitment to ensuring equitable global access to the advances scientific innovation delivers. They are unwilling to accept the status quo and are continuously driving toward a better, healthier world.

An edited version of our conversation appears below.

Let’s start at the very beginning. Take us back to 1995. What made IAVI unique in the early days?

Berkley: I think what made it special was that there was a focus placed on the developing world. The consensus was that we needed to focus on the places where the disease was spreading the fastest.

But we didn’t just want to do research in developing countries, we wanted to empower scientists from those countries to do that research. That has a number of advantages. It helps in the actual research itself, because then you have the trust of the communities, as well as local engagement and leadership. It also creates sustainability. We’ve seen that many of these sites today not only work on HIV but also work on many other diseases. That is a really important part of what was done.

One of the things that made us most proud was the quality of the trials and the work that was done. When there were problems, they were solved locally. That is really some of the best work we can do to help empower communities for future outbreaks. Global health security is about building capacity across the world.

Feinberg: I completely agree. I think that IAVI’s engagement with developing countries and USAID’s [U.S. Agency for International Development] involvement though their support of IAVI have been critically important. And while I think more and more organizations are now embracing the philosophy that Seth articulated, it’s surprising how long it’s taken and that it isn’t more of a routine endeavor because it is so important build sustainable scientific and clinical research capacity in country.

The scientists and public health workers there are the best connected to the communities and they best understand the needs of the communities at risk of these diseases. That is critically important because otherwise you can come up with innovations that are not going to be accepted because you have failed to win the trust and engender the confidence that people need to really embrace new innovations.

Berkley: Another factor that made IAVI unique was making sure that we had people who knew how to develop products in addition to doing the basic science. That focus on the product development side was a special niche. It was really about trying to do things at a different level of magnitude. Even in the animal work we did, it was about doing things on a larger scale so we could have statistically significant answers.

We were also trying to pursue a different funding model. Rather than relying only on research funding, we wanted to have large amounts of finances that could be placed on some big bets.

One of the challenges of starting a new initiative in a completely new field is to get people to support you. And, of course, we started with philanthropy. I will never forget when we got the first check in the mail signed by Bill Gates Sr. — it wasn’t even the Bill & Melinda Gates Foundation in those days — and the note with it said, ‘from time to time, let us know how things are going.’ That was the reporting requirements for our first grant! And as the Gates Foundation became a bigger and bigger supporter, I remember Bill Sr. saying, with tears in his eyes: ‘If this isn’t what philanthropy should be used for, then I don’t know what is.’

That funding went to use right away. Within 10 years, IAVI had sponsored the testing of five vaccine candidates in 11 countries. Did either of you think we’d be here 25 years later still talking about IAVI’s efforts to develop an HIV vaccine?

Berkley: No, at the time I had hoped we would have solved it quicker. It seemed like we were always 10 years away. And I think the challenge is that we didn’t fully understand the difficulty of the science. That became much clearer, a lot of that due to work done at IAVI, and I think this is allowing scientists to approach some of these difficulties in new ways.

Feinberg: The COVID vaccine example has made everyone think that it’s possible to make vaccines against every pathogen in a very short period of time. But no one really knows how long it’s going to take to make an efficacious HIV vaccine.

Seth and I, and many others, have been doing this for a long time and I think that at the beginning of our careers we had no idea that we would be doing this for so long. And it’s clearly going to take a lot longer. But the progress that’s been made is amazing, and, in many ways, it does what Seth alluded to — it clarifies why this is so difficult. You never know when you’re going to have that breakthrough, but we can’t count on being lucky. We have to do our best to be as smart as we can. I think a lot of effort is going into that and progress is being made.

Berkley: Sometimes science can move quickly and sometimes it takes longer. But at the end, it’s critical that we trust the power of science — that’s the only way we’re going to solve these problems.

Science and innovation have been critical to IAVI’s mission. Once it became clear that an HIV vaccine wasn’t going to be an easy win, IAVI established various efforts to address some of the major barriers to progress. This led to the establishment of the Neutralizing Antibody Consortium and, subsequently, the Neutralizing Antibody Center at Scripps Research. How have these efforts shaped the HIV vaccine effort today?

Feinberg: When the Neutralizing Antibody Consortium/Center was first set up, the goal was to understand the nature of broadly neutralizing antibodies and to use them specifically as a tool to inform vaccine immunogen design. And it’s done that in an amazingly successful way. Those vaccine concepts are now in the clinic and being tested. Hopefully, they will be refined and validated, and will be key elements on the path to an efficacious vaccine.

The idea that was at the heart of the NAC was to bring together scientists with insights into many different disciplines that are relevant to vaccine development and connect them to the populations who are either infected with or at risk of being infected with HIV, as well with scientists in the communities and countries where the disease burden is greatest. That really had not ever happened before. At that time, this kind of multi-sector, multi-disciplinary collaboration had not really been used in biomedical science, especially in the global health arena.

The list of accomplishments that have come out of this collaborative effort is remarkable and it would not have ever happened without making connections across different geographies and disciplines. It wasn’t just the science. It was the model of doing this type of innovative science. This has become a more common model today. Even if you look at the COVID-19 response, a lot of the progress that has been made so quickly would not have happened without multi-disciplinary approaches.

Berkley: Even going back to the beginning, one of the things that IAVI did was to go out looking for innovations in biotech. One of the most important ones early on was a company called Theraclone Sciences that had the ability to do high throughput isolation of neutralizing antibodies. That led to some of the early breakthroughs that allowed new broadly neutralizing antibodies to be identified. This then led to a flurry of activity in other labs as well to create a whole family of broadly neutralizing antibodies that were absolutely critical to understanding the targets on the virus, which then led to some really spectacular structural biology work. So all of this is the result of a long trail of investments that led to further advancements.

How has IAVI evolved and expanded its mission since then?

Feinberg: It has evolved in significant ways. One element in IAVI’s evolution has been that these tremendous capabilities that were put in place to advance HIV vaccine development also have relevance to other targets in global health, many of which are much easier targets than HIV itself. So IAVI has since taken on many of those challenges. HIV is the discipline that drove monoclonal antibody discovery and optimization technologies to a state of sophistication, which is quite amazing right now, and we’re applying that to other diseases of global health relevance.

The idea also emerged over time that the HIV antibodies themselves could be a useful tool as long acting, pre-exposure prophylaxis to protect people at risk of HIV from becoming infected, as well as possibly treating or curing people with HIV infection. That remains to be demonstrated, but it did set a vision that had evolved from this being a tool for immunogen design to this being a public health intervention that could be available to meet the needs of people living in low-income countries.

Another approach that was employed at IAVI’s Vaccine Design and Development Laboratory was to focus on live viral vectors and to try to understand which ones would be most effective for an HIV vaccine. The lab settled on vesicular stomatitis virus [VSV] as a broadly applicable and promising vaccine vector candidate, and now we have very promising programs. We have a VSV Lassa fever vaccine that is in the clinic and we have a VSV Marburg vaccine that’s going to be in the clinic next year, we hope, and we also have an Ebola Sudan VSV candidate in development. We also developed a VSV SARS-CoV-2 vaccine candidate in partnership with Merck, which didn’t yield promising results in the initial study, but we are optimistic that we can develop a vaccine candidate that might fill some of the gaps that exist with the first-generation candidates.

How has the focus on access been critical to IAVI’s mission?

Berkley: Early on, IAVI tried to bridge not just the science but also advocacy. The goal was to involve activists and to have a good communications strategy so we could get information out to the people who needed it. Part of this was getting access on the agenda and having it be a critical piece of our strategy because we knew if we didn’t plan for it ahead of time, it would never happen.

Feinberg: Access is one theme that has been constant throughout IAVI’s history because innovation in its own right is meaningless unless it can be available to everyone who needs it.

IAVI is taking on, as best we can, the work that needs to ensure equitable, timely access to innovations that are relevant to people all around the world, including in low-income countries. We’ve built partnerships that not only to bring in the best technologies to support the work in the monoclonal antibody and vaccine space, but also that can help facilitate affordable and scalable manufacturing.

But even the best-laid plans for access seem to be difficult to carry out, as we are seeing with COVID-19 vaccines.

Berkley: Of course, with COVID-19, we knew, given what happened with swine flu, that it was likely that wealthy countries were going to buy up all the vaccines. We tried to design a program based on all that we’ve learned over the years to prevent that from happening, but it was very hard given the fear that was associated with this disease. High-income countries wanted to protect their own populations and invested heavily early on, making it difficult for others to have access. So, this work on access continues, and it’s going to have to include scientists and clinicians around the world to make the case that improvements in technology and science need to be brought to the world. It’s really the same movement that we started at IAVI so many years ago.

Feinberg: I think the history of HIV has set many positive precedents in the access space. Global access to antiretroviral therapy transformed the way people think about access to innovations and equity, and that’s incredibly important. But access needs to be a core element in how one thinks about the product development continuum because you really need to have access front and center in your mind when you start developing a product, otherwise you may end up in a place that doesn’t really enable access.

Access is not the responsibility of any one organization or any one sector. It’s really everyone’s responsibility. We need to figure out how to get people aligned from the beginning to make sure that access happens as widely as possible, as quickly as possible.

Has the public-private partnership model employed by IAVI been an effective way to stimulate innovation and access?

Berkley: I think there is no question that it has been successful. For HIV, it has been able to drive important basic research, clinical research, and design work in a way that has complimented what’s going on in other places and brought in interesting partners to move things forward.

I think there are many examples of very successful public-private partnerships. Gavi has managed to bring together public and private sectors to dramatically increase immunizations, reduce vaccine preventable deaths by 70%, and make immunization the most widely distributed health intervention in the world. That cannot happen without industry, but it also can’t happen without the public sector.

My own belief is that great advances are not going to be made by government, or the UN [United Nations], or the private sector. They are going to be made by interesting combinations of those and others working together. That is the only way we are going to solve big problems.

Feinberg: I think collectively we are getting better as public and private sector entities at working together, but the best days are ahead of us in that regard. And, unfortunately, sometimes it takes a crisis to force the issue. We’ve learned a lot from the responses to HIV, Ebola, and COVID. Now we need to take these learnings and really figure out how to put them together into a strategic framework so that each sector contributes in a way that works best and most realistically for them.

I believe that this is a very promising time now with IAVI’s 25th anniversary to think about how to take that model to the next level. Multi-sector collaboration is not only the most promising, but really the only solution likely to be successful for these challenges.

Berkley: I agree with Mark. As we have more and more frequent outbreaks, and as more and more new pathogens appear, we’re going to have to be able to jump on those and this is one of the best models for doing that.

And what is IAVI’s role in that over the next decade?

Feinberg: If I ask myself, what do I want IAVI to be known for? I’d really like it to be known for being not only a great organization scientifically, filled with compassion and a commitment to equitable access, but an organization that’s really good at imagining and implementing new models of collaborative research and development efforts to address the needs of people who would otherwise be left behind.

The organization that I took over in 2015 had so many great elements that could be brought together and what we’re trying to do now is pilot new approaches that others might want to further build upon and refine in the future.

What inspires you both to keep doing what you’re doing?

Berkley: It is the right thing to do. And when you look at the world, you realize the power of science can make such a difference to people. But market forces help make a difference to people in wealthy countries much more easily than it can for people in developing countries, so making sure that the science that comes out can get to everybody who needs it, and even be specifically designed to work in the places where it can make the most difference, that is really what drives me to keep going and make the world a fairer and more equitable place.

Feinberg: I’m fundamentally an optimist. And I know that Seth is too because otherwise we wouldn’t do this kind of work. I’m optimistic that we will have even better models that will become more proactive and more impactful so we will deliver solutions to currently unmet needs, and we will make them available to people faster than what has previously been the case.

This is a great position to be in, where you get to think about interesting science, but you also can think about how that science can make lives better for many people around the world and save the lives of many people around the world.

And since we are commemorating an anniversary, can you both share your favorite memory of your time at IAVI?

Berkley: I have a million best memories of my times at IAVI. But one I particularly loved was when we were looking at doing very sophisticated T-cell assays across the world and we were at a seminar looking at the results from these analyses, and there were a lot of bumps in some of the results suggesting not very clean data. And then there was one result that had absolutely clean, perfect data. And I remember that everybody thought that clearly it was the Oxford lab that had the best data. But it wasn’t. It was the Rwanda lab. And I remember just thinking, wow, even with all the difficulties, they had the best results. That just made me so proud and showed me that we must have inclusive science.

Feinberg: For me it’s just the constant opportunity to work with an amazing group of people who genuinely care about making the world a better place.

Listen to the conversation between Berkley and
Feinberg in the latest podcast episode of Inside IAVI.