JOE PALCA, host:
From NPR News, this is TALK OF THE NATION: Science Friday. I'm Joe Palca.
For the rest of this hour, we'll be talking about AIDS vaccines. This weekend, the 16th International AIDS Conference opens in Toronto, Canada, and vaccines are bound to get a lot of attention, and particularly the question of how to make an effective vaccine against HIV, the virus that causes AIDS.
Progress on vaccines has been frustratingly slow. The virus is tricky, and traditional vaccine strategies haven't worked very well, if at all.
Ten years ago, one medical doctor decided that AIDS vaccine research was moving too slowly. So Seth Berkley started the International AIDS Vaccine Initiative, known as IAVI, to try to accelerate the search for something that would work, something that would stop the misery caused by AIDS.
Dr. Berkley joins me today to discuss where we stand for the hunt for an AIDS vaccine. He's the founder and president and chief executive officer of IAVI. He's also adjunct professor of public health at Columbia University in New York. Welcome back to Science Friday, Dr. Berkley.
Dr. SETH BERKLEY (International AIDS Vaccine Initiative): Nice to talk to you, Joe.
PALCA: And if you want to join our conversation, please give us a call. Our number is 800-989-8255. That's 800-989-TALK.
And so just to start, why is the AIDS virus so tricky? I mean, people, you know, there was that famous speech by Margaret Heckler in, I guess it was 1983, saying now we've got the virus and it'll only be a matter of a year or two before we have a vaccine. And, of course, that was optimistic. But still, 25 years, you would think, or maybe you would think, that you'd gotten further than we've gotten. Why has it been so hard?
Dr. BERKLEY: Well, this is really one of the toughest challenges, the toughest viruses we've ever really come against. In addition to that, there's some policy issues. But let me first start with the science. And that is this virus is constantly mutating and changing. So it's almost like you're, you know, you're seeing a new virus every time, you know, a new person is getting infected, and even within a person.
Secondly, this virus has all these techniques to keep the immune system from seeing it. It's coated in sugars, which, you know, make it not very immune-responsive. It also integrates into the host. So it hides away inside cells for a very long time.
So, you know, compared to virtually anything else that's been out there, this is one of the toughest. And the fact that it targets the host immune system itself means that, you know, the system that would protect against it is the thing it's going after.
The last part of this is that, you know, and the way we've found the way to other vaccines, to solving this, has been by looking at natural infections, natural immunity, people who got infected and then became immune and, you know, what correlated with that. In this case, we don't know of any people who got HIV and later on became immune. So we've basically got to do better than a natural infection.
PALCA: So, let me just be clear. There doesn't seem to be anybody who's become infected, measurably infected, and then for whatever reason got rid of the virus completely?
Dr. BERKLEY: That's correct. Now, what we do have are people who are called long term non-progressors. And those are people who get infected and manage to keep the virus under control for a very long period.
We also have people who have been exposed many times and don't get infected. And there's pretty good evidence to suggest that, you know, these can both be related to an immune response. And that's one of the main things that gives us hope.
We know that people, even the average person when they get infected, has a seven to 10-year period before the disease overcomes their immune system and then they go on to die unless they're, of course, treated. That period, the virus is held in check by the immune system.
PALCA: It's not as if there are not any AIDS vaccines out there. There's, you know, several, if not dozens, that are being tested, and at least one that's in large-scale clinical trials. I mean, are any of them likely to be the vaccine that we will use?
Dr. BERKLEY: Well I suppose it would shock the listeners to know that despite 25 years of this relentless epidemic, only one vaccine type has been fully tested to see if it works. Now when I said at the beginning there are policy issues related to it, clearly the greatest challenge is science.
But for a long time, people were focused, in a way rightfully so, on trying to get treatments for this disease, even though, you know, we didn't know how to do that, and so there wasn't a lot of attention on trying to drive vaccines forward.
That has recently changed and, you know, when we started IAVI 10 years ago, the world was spending about $150 million world wide, public-private sectors. That number this year in our last accounting was $759 million, so that's, you know, a huge increase, and a doubling, in fact, in the last five years.
So a lot more attention, a lot more effort, and now about 30 different vaccines in clinical trials, including one that we're particularly excited about that the Merck Corporation will have information on its efficacy in 2008 time range.
PALCA: And we think about, I think most people think about vaccines as being, you know, completely protective, which is to say you get the vaccine, you get exposed to, you know, chicken pox or whatever, you get the chicken pox vaccine, you don't get chicken pox. But it's possible that people should be thinking about different models, and maybe vaccines that are not 100 percent effective at blocking infection.
Dr. BERKLEY: That's absolutely true. First of all, I mean, not all vaccines are 100 percent effective. In fact, most are not. And we have vaccines, and traditionally, I mean, the flu vaccine, cholera vaccines, typhoid vaccines, that have had different levels of efficacy.
The most important thing about vaccines is the public-health effects they have, because if you vaccinate a community, what you basically do is drive away the disease, and that protects even those who might have a vaccination that isn't quite taken, and so they don't have protection themselves, or even those who might not have been vaccinated.
So that so-called herd immunity is what we're looking for, and it can be quite remarkable. When they introduced haemophilus influenzae type B in the United States, you know, we saw when it reached about 30 percent of the population, the disease began to disappear across the entire population.
But to get to specifically your question, it may be that we'll start off with a partially effective vaccine. Is that is targeted to those at highest risk - HIV itself is fairly difficult to transmit sexually, so if you could reduce the transmission rate in that population, you could have a dramatic effect on the numbers, and modeling has shown that a vaccine with an efficacy as low as 30 percent would have a dramatic effect on reducing the spread.
PALCA: So even if only one in three people were protected, that would still reduce the spread of the virus. Is that what you're saying?
Dr. BERKLEY: Absolutely, and in addition to that, obviously there are different types of vaccines. The perfect vaccine would be one that, you know, protected against infection. So you have the vaccine, if you're exposed, you didn't get infected. And that's called sterilizing immunity. And that's the goal.
But if we had a vaccine that didn't protect against sterilizing immunity, but instead protected against the disease AIDS. In other words, you got infected, but the virus was kept in check. That would be a secondary goal and that would be good.
And a third one, which is the least desirable, but again, would make a difference, would be one that blocked transmission. So in other words, you've got infected, you would go on to develop disease, but by creating some immune response, then the person wouldn't be able to transmit it. That's called a public health vaccine. And of course that would, you know, have a dramatic effect on the epidemic, but not on the individuals.
PALCA: We're talking with Dr. Seth Berkley. He's the founder of IAVI. It's an organization trying to spur the development of an AIDS vaccine. We're taking your calls. 800-989-8255. 1-800-989-TALK.
And let's take a call now from Kim(ph) in Stanford, California. Kim, welcome to the program.
KIM (Caller): Good morning. I'm with the agency Asian AIDS Action, and I've been closely involved with the - sorry, ACPU, the clinical trial groups happening in D.C. since the early ‘90s. And throughout the ‘90s, physicians from the U.S. would come up about the protocols, and invariably, the people they would be testing them on would be gay white men, and gay white man, and gay white men, and no people of color and no women, ignoring the fact that the AIDS virus that afflicts most of the people internationally, that 98 percent of the people who are living with HIV and AIDS are non-gay and non-white.
You know, why are we surprised that 25 years have been squandered? It's going to take another 25 years before anything emerges, because even today, most of the funding that goes to research institutions like Stanford and elsewhere are not focusing on viruses in populations around the world.
And what is sad is when the Global Fund was founded, advocates, and essentially gay, white AIDS advocates in the U.S. still resent money going to Africa and Asia. 98 percent of the people living in the world with HIV and AIDS are non-gay and non-white.
PALCA: Okay, Kim, Kim. Interesting point. Let met get Dr. Berkley's reaction to that.
Dr. BERKLEY: Well, Kim, I certainly agree with you, and from the founding of IAVI 10 years ago, we only focus on viruses spreading in the developing world. In fact, we were the first group to create an AIDS vaccine for Africa that was made from the local circulating strains, and since then we've done that with six other vaccines, novel vaccines, taking them into humans, and we're doing trials now in 11 countries.
Of course we don't know the significance of the different populations and the different viruses that are circulating around the world. Obviously, we need a vaccine that's going to protect against, you know, all forms of the virus, against all roots of transmission, and in all populations. But since we don't know the significance of it, it's critical that we do research in these parts of the world. In addition, these are the places where you can get the answers the quickest, given the fact that the incidence is higher there.
PALCA: Right. But Kim's question raises the difficult point, which I'm sure you have given a lot of thought to, is let's say that all this research does lead to Merck creating a successful, or some other company, creating a successful vaccine, however you define success. You have to give it to a lot of people, and it's going to be expensive. So how does that work?
Dr. BERKLEY: Well, let me give you two answers to that. In our own research, since it is publicly financed, we negotiate deals with the companies, both large and small, that we work with, such that in exchange for the investments and works that go on by these public-sector dollars, they agree to give access back for the public sector of the developing world, and they agree to provide vaccines, you know, at reasonable cost, reasonable quantity and reasonable speed, and all of that is defined. If they don't do it, then we have the right to have somebody else manufacture it.
So in essence, we're building that in. But, you know, for even a commercial vaccine, the challenge is going to be a time-line issue, because all vaccines eventually make - you know, trickle their way down, and as a vaccine gets older and more mature, what happens is you get to manufacture it better, and the cost comes down, and the marginal cost to producing extra doses is low.
So the challenge, really, is instead of waiting 20 years until we get to that point, is to try to do that up front, and there's been a lot of innovative policy work that's going on, including by the G8, to create these advance market commitments as one example of a way to do this, to try to encourage that type of industry pricing from the beginning.
PALCA: We're talking with Dr. Seth Berkley. He's the president and chief executive officer of the International AIDS Vaccine Initiative, IAVI. We're taking your calls at 1-800-989-8255. That's 1-800-989-TALK. And I'm Joe Palca, and this is TALK OF THE NATION from NPR News.
Let's take another call now from , let's take a call from Justin in Corvallis, Oregon. Justin, welcome to the program.
JUSTIN (Caller): Hi. Good to be on the show.
JUSTIN: I know that there are certain populations around the world that have been found to be resistant to the disease, and I believe this is because they lack a certain cell receptor that the AIDS virus attaches to when it's infecting a cell, and I'm curious specifically what sort of research has been going into that area, and if that would involve vaccines or other sorts of treatment.
PALCA: Justin, good question. Dr. Berkley.
Dr. BERKLEY: Yeah, I mean, the interesting thing of course is there's no group that is completely resistant, and initially there was a lot of concern. You know, you have, the epidemic existed only in a few areas of the world. There were a lot of people who stood up and said, you know, we're resistant, or we have different behavior, or you know, our society is different. And of course it turns out that this disease exists in every single country and in every population.
What Justin's referring to is in northern Europe, there are certain populations that have a mutation in one of the receptors that HIV targets, and for those particular people, it's extremely hard for them to get infected, and so that does exist, it's in a small group of people.
It's been a little bit of, I will say a research finding, rather than as a practical benefit, because you know the hope was that when we went and looked at other people who didn't have infection, it might be because they also had these mutations, and it turns out not to be the case.
Now that being said, the identification of these types of natural resistance allows you then to begin to target drugs and antibodies to these specific receptors, and that's really how we make breakthroughs, but it's not an incredibly common phenomenon.
PALCA: So, I mean, how are you feeling right now after 10 years at this. Are you encouraged at the progress that's been made, or discouraged? Do you think that people are coming at this with enough creativity? Because it seems as if a lot of the vaccines that are out there are sort of similar in nature.
Dr. BERKLEY: I think that's correct, and so I am encouraged by the advances that are occurring in science. I'm an impatient man. The issue for me has been the speed at which this is occurring, and what's beginning to happen now, and the big change is that not only is there additional money, but people are beginning to go back and work on rational vaccine design in addition to scientific empiricism, and that combination is what's critical.
On the rational vaccine design, people are beginning to say, well, you know, we did this high-throughput screening with drugs. Maybe we could begin to use some of those tools on vaccines, which are closer to biologics. And so, you know, taking this kind of bleeding edge science and putting in place is really useful.
We in our neutralizing antibody consortium just bought, with Scripps Institute in La Jolla, the world's largest crystallization robot that is specifically going - and this is very bleeding edge science - to make the types of neutralizing antibodies and look at the structures of them so that we can try to figure out how to make better vaccines. And so pushing that type of technology I think will make a difference.
PALCA: Okay, one more quick call: Ted in Oakland, California. Welcome to the program.
TED (Caller): Hello. Well, my question is, and my perception is that prior to AIDS, there was only one way to attack a viral infection, was see if you could develop, isolate the virus, develop a vaccine and then inject the population. And one of the things that I've seen, and I don't know if this is true, which is my question, is that with AIDS, people have taken an idea that, well, maybe we can attack the viral infection where it, after it's already infected the cells, and so we see many more anti-viral drugs than we ever did and much more research in that area.
PALCA: Ted, interesting.
TED: I'll take my answer off the air. Thanks.
PALCA: Okay, great. Dr. Berkley, what about this post-infection vaccine?
Dr. BERKLEY: Well, he didn't say vaccine, and I think he's absolutely right. I mean, as Tony Fauci likes to say -
PALCA: Tony Fauci, the head of the National Institute of Allergy and Infectious Diseases.
Dr. BERKLEY: Right, absolutely, that you know, when we started, there were, you know, only a few licensed anti-viral drugs, so when people said let's make drugs for viruses, people said, you know, that's not going to happen. But, you know, the activist community pushed really hard, and there are now more anti-viral drugs licensed for HIV than for all other viral diseases put together, which just shows the power of science when it's really focused down on a problem, even when there's initial skepticism.
So that has been a new technique. The problem is that the virus is constantly mutating, and so when you get resistance, which you will even if you take the drugs perfectly, the second-line drugs, you know, are more expensive and tend to be more toxic, and then of course you're eventually going to need third-line and fourth-line. So you're really chasing this virus, which is constantly mutating, and eventually you will end up with, you know, viruses that are resistant to all drugs.
So we see that as an incredibly important thing, but it's only really a Band-Aid. What we really need to do is develop a vaccine, which can stop the epidemic altogether.
PALCA: Dr. Berkley, we're out of time. Thanks very much for joining us.
Dr. BERKLEY: Thank you very much.
PALCA: Dr. Seth Berkley if founder, president and chief executive officer of the International AIDS Vaccine Initiative, or IAVI.
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