At the XVII International AIDS Conference in Mexico City, David Evans
talks with CEO and President of the International AIDS Vaccine
Initiative, Seth Berkley, MD, discussing what we've learned about the
challenge to build a better vaccine after recent vaccine failures and
next steps in research and advocacy. Click here to view the video.
David Evans: Hello, I’m here today with Dr. Seth Berkley, who is the President and CEO of the International AIDS Vaccine Initiative and a professor at Columbia University and Brown. Welcome, Dr. Berkley. So, the other day in one of the sort of kickoff sessions about vaccines, Mitchell Warren characterized the STEP trial. He said it was important to look at it differently than it sometimes been reported, that the candidate vaccine may have failed but the trial was a successes. Would you characterize it that way as well?
Seth Berkley: Well, it’s complicated to talk about that particular vaccine because as you know there has been some question of perhaps people who received the vaccine and who were preexposed to the Ad5 virus and were uncircumcised might of actually had a higher risk of infection, so in that case you would obviously worry about the trial and that particular candidate. But the point that Mitchell was trying to make, which is absolutely right, is that although the candidate failed we learn an enormous amount from these trials. In that particular case, people had, had two different animal models before. One candidate worked with the animal model, didn’t work the other and so we were able to say the one that did work with is probably not valid as an animal model. We also learned that the normal blood test we use to test the potency of these vaccines, the gamma interferon ELISPOT, was probably not a predictor because Merck gave very good levels of gamma interferon ELISPOT. That will allow us now, in the next vaccine, to design it better and not have those same problems, mistakes. So that’s what he meant by the learning process.
DE: Speaking of the next vaccines, I’ve read a lot about going back to some basic science to try and find a number of broadly neutralizing antibodies and ways to get the body to induce them. Is that where we are in terms of the next vaccines, is back to some basic science first?
SB: There are two issues there. What Tony Falcci said is to tweak the knob back to basics. The big point, of course, is that HIV is a disease in humans so at the end we have to do clinical research, it’s part of the discovery process. The issue is not to go completely back to basics and abandon the work that’s going on, but what we believe is that one has to go back now and try to make better vaccines. The current generation of vaccines have been directed at cellular immunity and we need to continue working on that and we’re looking at more potent vectors that might give cellular immunity. But at the same time the Holy Grail is the neutralizing antibody, that’s the way most vaccines work and we actually know that humans can make them because we’ve isolated them from people, actually HIV positive people who have been infected for a number of years, usually not on treatment, we’ve now identified a number of them and we’re looking for more. The question though is what do you need to inject to get those types antibodies but if we can get them we believe they would work.
DE: In terms of the second end point of the STEP study, which was if we couldn’t protect someone from becomng infected perhaps we could help ensure that they were not a rapid progresser. Are there some candidates in the wings that we think might help that happen?
SB: Well actually all cellular immunity candidates probably will work by preventing disease, or slowing down disease, because that’s what normally holds the virus in check so when somebody gets infected they end up with a cellular immune response, that holds the virus down, and only when their own immune response weakens or they get continued escape mutants that eventually the virus takes off. Actually Merck as a candidate would have been thought to work that way, it didn’t, the viral load was the same in the two groups. Although there is some intriguing data that suggest perhaps in some small sub-groups there might have been some differences and people are looking at that, but sub-group analysis is always fraught with dangers. So the other cellular immunity candidates that are in the pipeline now that are still being looked at, would do exactly what you described.
DE: Would the next step with those candidates be some of these smaller phase 2 studies in humans to see what actually happens when we give people the vaccine?
SB: When we released our blueprint here, which we do every two years, what we argued in that blueprint was of course to try and solve the neutralizing antibody problem and move to better vectors or cellular immunity. What we argued is that you basically got to compare because now we have a bar, the bar is the Merck candidate, so show us that candidate is likely to be better and there’s many different ways – it targets differently, its much more potent or in the animal models that look better it has a dramatic affect then you say ‘absolutely, that looks better’ and then of course you want to move it as fast as possible into human testing but not big licensing trials now. We want to go back to having smaller trails that will give us an answer. Is there any promise here at all? If there is do everything we can to move it quickly. If there’s not, throw it away and look at the next candidate.
DE: Two more questions, the first is, and I’m not to sure I have it exactly right because I capture it off of a press release, that there were some data being released that showed that in, I think it was African Green monkeys, they found that the antibodies did not help control viral load. I’m not sure if I got that, maybe you haven’t seen that study.
SB: No.
DE: No? Okay, then the second question is from an advocacy standpoint…
SB: Well let me just comment. The problem has been the VaxGen vaccine, you have the first vaccine that didn’t work, hundred percent of people got antibodies. The issue there was that they did not neutralize primary isolates they neutralized the lab-adapted strains. One of the challenges is everybody got antibodies, in fact the antibody test, you know the test for HIV, is an antibody’s test. The challenge is that those antibodies aren’t neutralizing the strains that are circulating, so I have no doubt that in some experiments in monkeys you’ll get strains that aren’t going to neutralize. What we’re trying to do is get antibodies that will neutralize all strains or a vast majority of them and then you can create a cocktail of them to cover all the strains
DE: In terms of an advocacy strategy moving forward in your blueprint what are sort of the first steps that we’ll be taking as activists to try and push the vaccine field where it needs to go?
SB: I think the critical thing… The bad thing that happened this year was a lot the media came out and said , you know, the second candidate in humans failed—only the second—and we have to abandon the effort, we have to stop, we have to give up, we haven’t learned anything—none of that’s true, we’ve learned an enormous amount and science will prevail. Just like with antiretrovirals, which scientist said we didn’t know how to make in the beginning and the activist by the way were the ones that forced them to invest and work in that area. We now have more drugs for HIV than for all the viruses put together. We need that type of activism. We need the community – HIV positive and negative- to say, ‘Yes, we need drugs. Yes, we need to do the best we can today with the tools but we want to see the end of AIDS, we want to see the next generation to be free of AIDS’ and the only way to do that is with a vaccine. So that would be my message on that.
DE: Any parting thoughts for our viewers, who are mostly people living with HIV?
SB: The one other point to make is that it isn’t not only about the next generation. Understanding how to create strong immunity against HIV will ultimately be the key component to doing therapeutic vaccination. The reason that its hard to do therapeutic vaccination, we don’t understand how to get really good immune responses and of course, because once the virus sets there its mutating all the time. But if we can figure out how to create broad based community then we can go and use those as therapeutic vaccines. And I think that’s going to be critical because vaccines might have the ability to train the immune system to work, to deal with some of this issue of resistance that’s occurring and also, might be an adjuvent to working in poorer communities where the existing difficulty of treatment and getting it out is going to be a problem. We don’t have that in hand today, but that’s part of the advantages that will come from the study.
DE: Okay, well fantastic. Thanks for taking the time.
SB: Thank you for having me.
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