Q&A with Seth Berkley: The search for an AIDS vaccine

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Before his talk posted today, the TED Blog talked to epidemiologist and founder of the International AIDS Vaccine Initiative (IAVI), Seth Berkley. He told the story of the beginnings of IAVI, exploring why different decisions have historically been made in response to the HIV pandemic and explaining why a vaccine makes sense today. Read on to understand how we’ve progressed in the way that we think about treating AIDS and other global-scale viruses.

It seems like we’re close to the end of the race for AIDS and flu vaccines. Have there been any developments since you talked at TED in February?

On the flu side of vaccines, I was very disappointed by public concerns that we ordered too much flu vaccine and that some might get wasted. At the time those decisions were made and vaccines ordered, we had no idea of the severity of this particular epidemic (H1N1). In the US alone, somewhere around 50 million people or more ultimately got infected and there were a number of deaths. It turned out not to be as severe a pandemic as in 1918, but early on, when the first cases were seen in Mexico there were a lot of mortalities in young adults, which should make you very nervous. So, I think that both declaring this a global pandemic and accelerating vaccine production as quickly as possible were the right decisions. If you want to prepare a population for an emergency it means that you might ultimately spend some money that isn’t used. That’s part of the process. I worry that there’s going to be complacency going forward, that people will say, “Look what happened last time. Maybe we shouldn’t order as many doses.” If it turned out that this was a much worse flu, there would have been worldwide clamor for doses. One last point on that is that the amount of vaccine made available to the developing world was extremely limited, and had this been a really terrible pandemic there would have been massive deaths in those populations.

On the HIV side, it’s an extraordinarily exciting time. We’re really experiencing a Renaissance in AIDS vaccine development. At the time of the TEDTalk, I discussed this retro-vaccinology concept and the host of new antibodies that have been found. Since that time there have been three more found, some of which target different areas, and we now know that if you combine a couple of them, at least in the laboratory, you can neutralize all of the strains. And so there’s a real move now to both try to understand where these antibodies are binding better and how we can make proteins to make antibodies like this, as well as whether we give these antibodies passively or do gene transfers. We could go ahead and transfer the genes that make these antibodies and so have people make them, just until we figure out exactly what the vaccine looks like. And, even while that work is going on, there is the other piece I’d mentioned, which is that there are now a lot of vaccine candidates that look far better than the first candidate that had been tested in the past and didn’t succeed. In the pipeline, there are a number of candidates that look much better in the best of the animal models, and those are working their way towards humans now.

Can you give us some background on how the International AIDS Vaccine Initiative (IAVI) began?

Well, when AIDS first appeared people didn’t know what it was. You’ll remember that it affected mostly young gay men — it was actually called GRID for a short period of time, Gay-Related Immunodeficiency Syndrome and people thought it actually might be recreational drugs or other types of toxins. It was discovered, of course, that it was a virus in late 1983 and the virus was further described in ’84. At that moment, people said that the only way to deal with a virus was with a vaccine. And, at that moment, there was only one licensed retroviral drug. So, when people said, “Let’s move forward,” the newest vaccine that was out was Hepatitis B and that was the paradigm they followed. That was the first kind of biotech vaccine. They tried to take a little piece of the surface of the virus and use that, and what they found was that 100 percent of people got a good antibody response. However, it only neutralized the strains in the laboratory, it didn’t neutralize the strains that were circulating in the population. That’s why they pulled away from neutralizing antibodies — they didn’t know how to deal with the amazing variability.

Over time, the companies began to pull away from a vaccine because it was scientifically difficult, very politically controversial at that moment and it was mostly a disease of the developing world, and the combination of those made it not a particularly good approach, economically. Also, vaccines were not a particularly good business in those days as they were very inexpensive. The public sector was interested in vaccines, but the activists — and rightly so — said, “My God, people are affected. They’re going to die. We need treatment.” And science said, “We don’t know how to make treatment.” The activists continued to push, and that’s why we now have more drugs to treat HIV than all other viruses put together. That really accents the amazing effect of the population of activists driving this forward. That has become a model for all other diseases, where patient advocacy has really become important.

So, because of this, a strange thing happened in the early to mid-1990s. There was virtually nobody working on HIV vaccines. The world had dropped down to about 150, 160 million dollars total. Everybody in the world — basic research, public, private, small companies, large companies — not much of an effort. And so, at that time our role was to take a look at that and to say “Oh my God. We have to do something about this!” So, we went ahead and created a new initiative which was a public-private initiative using the best of industry and combining it with the methodology and ethos of the public sector, which put product development and access to the poor at the core of what it was doing.

It may not seem like a big deal today, because now everybody has public-private partnerships, but at the time IAVI was a really bold new idea. If you think about it, at that moment it hadn’t happened before. The places where you would do vaccine development for diseases such as HIV would be large companies and maybe large governments. The idea that an NGO would play a role in this seemed ludicrous. Also, this was pre-Gates Foundation, this was pre-large amounts of money, so the costs that were associated with doing something like this seemed way above levels that were plausible. It really was seen as a wild, bold idea.

You mentioned the political difficulty associated with a vaccine, could you elaborate on that?

The reason it was politically difficult was because all this activism was going on — companies were being picketed, blood was being thrown on researchers, and so concerned companies were thinking, “If we’re in this space, look at what could happen to us.” Now most of that was about treatment, not about vaccines, but the other side of it was that there aren’t constituencies for prevention, and this is a problem. If you really are effective in prevention, there’s no disease, so you’re invisible. Once you get sick, of course, a person wants to spend whatever they can to get better. So there’s enormous activism for treatment and people will spend large amounts of money, but for prevention it can be very hard to get both activism and also the long-term expenditure that’s required. Although drug development was obviously also a long-term phenomenon (it took many years for them to develop drugs), it was all of this activism and interest and pricing — you could price the drugs high because it was a fatal disease — that wasn’t there for vaccines. And so, it didn’t experience the same effect of attention

The main thrust of IAVI is the vaccine, but there’s also other work being done there. Would you like to talk about that?

We’re pretty focused on AIDS vaccines. We did a little bit of work on one other type of prevention treatment, just because we were in the right place at the right time and had the capabilities to do that, and that was pre-exposure prophylaxis using drugs, but virtually 100 percent of what we do is AIDS vaccine work. Now, as part of that we train scientists in the developing world, we build laboratories and then bring them up to world standards, we create situations where people get screened for HIV and then get referred for treatment if they’re infected. So, a lot of secondary benefits occur to the work, but like a laser beam we’re focused at preventive HIV vaccines.

The international work that you do at the Initiative is also very interesting. You’re in a huge number of countries, so how do you coordinate all these efforts?

There are two sides to that. We’re working in 26 different countries. On the research side, we’re very different than most laboratories. In a country or in a laboratory they do the best science possible to be able to solve the problem, and at a country level, country-based initiatives tend to fund the scientists in their country that are doing the best science possible. Our role is not to do that basic research, our role is to glean that basic research. But, it’s not based on country, so that if there’s a fabulous technology in Japan, Sweden or in Belgium, or in the US, our job is to find that technology and to try to drive that forward and then move it forward as fast as possible in whatever country can do so. Now, why is that important? Because what we’re constantly doing is asking, ”Where’s the best new technology?” It means not only taking up new technologies, but it means dropping old technologies.

So, we rely on national research efforts, but national research efforts don’t do the same thing as we do. By definition, the Danish government is going to fund the best in Denmark and the Canadian government the best in Canada, but not necessarily the best in the world. They don’t have a mechanism to look at how the Canadian vaccine is versus the Japanese vaccine. So that’s on the science side — we’re constantly looking to move forward and say, “Ok, where’s the best place to test these? Could we test them in a place that has good regulatory experience with this type of product? Where is there a high incidence of HIV? Where are vaccines needed?” That’s why we work across the developing world as well.

So, on the developing world side, we’ve set up a diversity of relationships with places with good science, but also places with different circulating types of virus. This allows us to not only test the vaccine in populations with different genetics, but also different circulating virus. And that’s why we’re working across Africa — in East, Central and Southern Africa — and not just in Africa, but also in India. Now, one of the other exciting things I mentioned is that as we’ve transitioned and done a little bit more upstream science, we’ve also tried to find places in the world that could do that. We’re doing a lot of exciting work in India now, in not only the first two clinical trials in India of AIDS vaccines, but also working with Indian biotech companies and computer companies to try to model this to do medicinal chemistry which turns out to be a skill that Indians have in large amounts because the previous major industry there was to copy drugs. So, they have a lot of medicinal chemists that were working on that, and as the new IT regimen came in and they weren’t doing as much of that, there were chemists who were very good who weren’t working as much. We can now get them working on these structural issues around HIV vaccines. And, we’re actually creating a new laboratory facility with the Indian government — a translational facility that’s going to be very similar to the lab that we recently created here in New York, in Brooklyn, that does similar work.

READ MORE: Seth Berkley talks about the brand new facility in Brooklyn, how small biotech companies are the new hotbeds of innovation, sourcing young scientists and why a vaccine is the only way. I didn’t know about the facility in Brooklyn. Would you like to explain what that project is about?

Well first, let me say a little about laboratories. From early on, we wanted to make sure that a vaccine trial done in Uganda was the same as a vaccine trial done in New York City or done in London, or anywhere else. So, we created a series of laboratories. We have 18 of them in the developing world that are absolutely state-of-the-art, and the people there are trained in good clinical laboratory practices, good clinical practices and these labs are fully accredited. To do that, we have a lab in London that acts as the quality assurance for the network. Initially, the way we worked was purely in partnerships, but we realized over time that there were some things the companies weren’t interested in doing, particularly if it was awkward or expensive to do them. So, we decided to do was to create our own facility, which was just one piece of this network. We haven’t moved completely away from partnerships, we continue to work in partnerships throughout the world, but this is one piece.

We staffed the Brooklyn lab with people out of the vaccine industry and we opened it in New York City at a place called the Brooklyn Army Terminal, which is a massive facility. It’s famous because Elvis went off to the war there, but it’s being recreated into a biotech facility at a different price point than others are — New York City is a very expensive place to work. So, we’ve got a very large lab there, a beautiful lab overlooking the Statue of Liberty on the water and we have pretty unlimited expansion space. The facility is massive, it’s the place where people went off to the Second World War and it’s a BSL3 (Biosafety level 3), which means it’s one down from the maximum containment Ebola lab. And, the city has built that with us as a partner and helped with most of the development, and so it’s been really successful. It just won an award actually, for entrepreneurship in Brooklyn.

One of the roles of the new lab will be to accelerate some of our other work and also to continue to help with some of the training work that goes on today to inculcate younger scientists into this forum, which isn’t really academic work. It’s what you’d call, in a vaccine company, vaccine discovery efforts.

Also, one of the things that’s changed over the years is that large companies used to be the place where all the innovation went on. Today, small biotech companies are the places where much more of the innovation happens. That changes the dynamics, because a large company makes a decision on whether to invest or not based upon whether it makes financial sense to them. But, for a small biotech company, even if they have fabulous technology, they don’t often have the capabilities to move that technology forward. So, we actually target these biotech companies. And, what’s really interesting about that is that we often target companies that aren’t working in the HIV vaccine space. We’re out looking for companies that are working in cancer, immunology or other aspects, and asking, “Is that technology relevant to HIV vaccines?” We identify them using a venture capital network, and then we go to the companies and say, “We know you’re supposed to be laser-beam focused on your product, but would you try an experiment to see if your technology can work for HIV vaccines?” One of the companies that joined us like this is actually one of the companies that discovered those new neutralizing antibodies I talked about at TED.

So, our constant question is: How do you bring innovation to the field and not reinvent the wheel, but take advantage of other efforts that are going on elsewhere? Because, in the HIV vaccine space we kind of don’t know everything that’s going on, it’s an unanswerable question. You never know what’s going on in other areas that might be relevant, so we try our hardest at figuring that out.

Are the members of the younger generation of scientists as invested in creating a vaccine as was the case 10 years ago or so?

Sadly not. A few years ago, MTV did a survey of the youth population and HIV was still one of the most concerning topics to their constituency. Obviously we’re in a world where sex isn’t as safe as it was, and young people think a lot about sex. So, that generation understands that it is an important topic. The problem is not that young scientists don’t think vaccines are incredibly important, the problem is that it is seen as such a difficult problem, such a long-term problem that what they’re worried about is: Can they build a career on it? Can they get the types of breakthroughs they need in a rapid time frame that would make it a productive place to work? And there’s been a lot of discussion in the community about how we can change those incentives, about how we can get grants that would be targeted to younger scientists to bring innovation into an existing field.

Also, you talk about asking other biotech companies who are working on other diseases to work on HIV — do you ever experience backlash for that approach because of the stigma that might still be associated with HIV?

In terms of companies, we’ve only had one time where there was a company — it was actually a company in another country — that didn’t want to be associated with HIV that wouldn’t share technology with us. But, it’s interesting. People perceive technology around vaccines as different. The staunchest conservatives understand that a vaccine can protect all groups. Obviously, you’d want to use it for high-risk groups, but you’d also want to use it in general population groups and people who are considered “innocent,” like those who receive blood transfusions, babies who receive transmissions from their mothers, those who are initiated into sex through violence or other issues. So, some of the people who might often be the most offensive about these types of issues, often find HIV vaccines to be important.

Also, from a public policy point of view, there’s great expense involved in dealing with the epidemic through treatment and reaching people when they’re already infected. The New York Times reported, maybe three weeks ago, that there’s been an extraordinary expansion of resources — a commitment made by the G8 that’s never been made before — universal access to HIV treatment. But this is a long-term entitlement program, because once you put somebody on treatment, they have to get treatment for the rest of their lives and they develop conditions, they develop toxicity and they need other treatments. So, there’s almost a sense now that all of the bright lights of that unbelievable effort — the unprecedented emergency program for AIDS relief, Bush’s triumph that people look on as being a great thing that he did, will create a demand that gets higher and higher and higher just to keep up with where we are.

And, let me just make a summary comment. I think that it’s really exciting that we’ve no longer live in a world where people die in their 20s and 30s, and have to have large families expecting that most of their children wouldn’t survive. And this isn’t only as a result of vaccines — it’s vaccines and better sanitation and better housing and a host of different things. But, we now live in a society where you can expect your children to survive and be healthy, and expect people to live into old age. And that’s the first generation of solutions, but there still are many of these diseases that are really terrible. We have the ability to create these tools, it’s just a matter of focusing our science and technology on them, and so it’s a really exciting thing to talk about. Even with the most difficult disease, an HIV vaccine, we’re really in a little bit of a Renaissance in terms of what’s happening and we need to make sure that in the long-term we continue to support this type of work, including the work in the developing world. With the amount of money being spent on vaccines as compared to treatment, it’s the only way you can end this cycle.