NEWSWEEK’s Laura Fording asked Dr. Peggy Johnston, assistant director for AIDS vaccines at the National Institute of Allergy and Infectious Diseases (NIAID) and a speaker at the conference, about recent developments.
NEWSWEEK: What’s the current status of AIDS vaccine research?
Dr. Peggy Johnston: Several dozen vaccines have advanced to the earliest-or safety-stages of clinical testing, in which the vaccine is tested in a small number of people who are not at risk for HIV infection. There are also four vaccines that are in the second stage of testing, which involves larger numbers of volunteers, including those in at-risk groups. But only one vaccine has advanced to the third stage of testing, which measures efficacy. It’s a product called AIDSVAX, and it’s manufactured by a small company in California called VaxGen Inc. The results from those trials will probably not be available until the end of next year.
How is AIDSVAX being tested?
There is a large trial going on in the United States involving over 5,000 volunteers who are at risk for HIV infection and have admitted risk-taking behaviors. Some receive the vaccine and some receive a placebo. They are counseled repeatedly throughout trial on how to avoid getting infected with HIV. Unfortunately counseling is not 100 percent effective and some of them continue to participate in some level of risk-taking behavior. So some will become exposed to HIV and infected. The trial will measure, in those who receive the vaccine versus those who receive the placebo, the difference in the number who become infected or whether or not the vaccine has helped protect the person from infection.
Is there any danger in giving these vaccines to people who do not already have the HIV virus?
All of the vaccines that have advanced to human testing cannot cause HIV infection or AIDS.
Do they contain the HIV virus?
No, they do not contain, nor have they been made from an intact HIV virus. All of these vaccines have been made by either recombinant genetic technology or by synthetic means. They contain only pieces of the virus and are missing parts that are essential to causing infection. So there is absolutely no chance of becoming infected from the vaccine.
How do these AIDS vaccines work?
Different vaccines work in different ways. The AIDSVAX, for example, is designed to stimulate antibodies against the virus, which, if successful, should block the infection. There are vaccines that are in earlier stages of clinical testing that induce a different arm of the immune system, called the cellular arm, or cytotoxic T lymphocytes [CTLs]. CTLs are specialized killer cells that seek out and destroy cells already infected by the virus. So AIDSVAX is made to bind to virus particles to prevent them from ever entering cells, while vaccines which induce CTLs kill cells that are already infected. Ideally we’d like to use both methods.
More and more, we hear that people are not being as careful about having protected sex because they think AIDS is less life-threatening than it once was.
It’s unfortunate that there appears to be this complacency about AIDS, that AIDS is a manageable disease now. I think anyone who has been on antiretroviral therapy for a number of years realizes that it’s no picnic. Even though these are very good drugs to control infection, there are a number of side effects and downsides. The bottom line is that not being infected is still a whole lot better than being infected and dealing with lifelong therapy on combinations of toxic drugs that you’ll probably have to take daily for the rest of your life.
Do you think any of these vaccines will be successful? When do you expect them to become available to the public?
I don’t think there is a lot of confidence in the scientific community that the AIDSVAX will be a home run. I think what everyone is hoping for [with these trials] is that we’ll learn more about how the body responds to the vaccines and whether or not any of them offer protection. One of the uncertainties we face in AIDS-vaccine development is not knowing the level of immune response needed to protect someone from AIDS. If we can find a vaccine that works, even a little bit, we can then evaluate immune responses. We hope that within this decade we can identify a vaccine that works at least some of the time, and then build on that to make better vaccines.
Do you see this as being a one-shot deal, where children might be immunized against AIDS?
Initially these vaccines would not be given during childhood. We are currently evaluating them in adults, and we’d have to go back and test them for safety in children. So that would take time. But who takes the vaccine might differ depending on people’s at-risk level, the cost of the vaccine, how often it needs to be taken and how effective it is. If the vaccine turned out to be highly effective and had no side effects, I’d imagine that many people who are sexually active in the United States would want it, particularly if it wasn’t expensive and its side effects were minimal. But if it were only partially effective and it had side effects people didn’t like, or if it cost $500 then, perhaps, only the highest risk groups would want it.
So you don’t expect to see anything within the next 10 years or so?
I’m hopeful that in this decade we’ll see something. Whether it will be in two years or in seven years, my crystal ball isn’t quite that clear.
Any idea how expensive a vaccine would be?
No, there are so many different vaccine designs. It will depend on which one it is, how effective it is and how often it has to be given.
If it works, do you see AIDS vaccines being used in places like Africa, where AIDS is raging out of control?
Well, it could be if the vaccine is affordable. I think the philosophy of offering them at a higher cost to those who can afford it and at a lower cost to those who can’t is going to have to become widely accepted, for an AIDS vaccine to stop the spread of AIDS worldwide.
Is this kind of thinking going on right now?
This kind of thinking has been in use for many childhood vaccines for a number of years. But even there we are talking about differences of tens of dollars, not hundreds of dollars, as could potentially be the case for an AIDS vaccine.
There have been reports that some Kenyan prostitutes were found to be immune to the HIV virus.
A report came out four or five years ago, saying that some prostitutes were highly exposed to HIV but remained uninfected and had cytotoxic T lymphocytes specific for HIV in their bodies. They seemed to have developed an immunity. However, a report earlier this year said some of the woman who had left prostitution had subsequently become infected. So apparently this level of immunity was not lifelong, and perhaps repeated exposure to the virus-this is only a hypothesis-kept their immune system going. Once they stopped having repeated exposure, their immunity may have waned to the point where they became susceptible.
Has anyone used that information to help them create a vaccine?
Yes, and that vaccine is now in phase I trials in Kenya.
Any specific AIDS vaccines that you feel most confident about?
That’s hard to say. Usually the ones that appear most promising are the ones on which we have the least amount of data to discourage us.
But do you think something will eventually work?
I’m confident that some of the vaccines in the pipeline will provide at least partial protection for some period of time. It may not be enough to warrant marketing, but it should give us some valuable information on the immune responses that are needed for protection. If we can find a vaccine that works in some people for a period of time, that alone will accelerate the field more than any other single finding. Many of the vaccines that are still in the pipeline, either in pre-clinical studies or in human studies, are very good at inducing cytotoxic T lymphocytes. But no one has yet devised a way to induce an antibody that is broadly reactive [to the many different strains of HIV]. I think that’s a problem that we’re going to have to solve in the research laboratories in the next couple of years. That’s where the excitement is going to be.
