TARGETING AIDS

	June 29, 2001
	Susan Dentzer reports on the continuing search for an AIDS vaccine.

RAY SUAREZ: Next, part two of our report on the search for an AIDS vaccine. Previously, Susan Dentzer looked at the factors that have held back vaccine research. Tonight, some of the more promising research now underway. Our health unit is a partnership with the Henry J. Kaiser Family Foundation. SUSAN DENTZER: 20 years after the first reports of the disease that became known as AIDS, roughly a dozen vaccines are now being studied for safety or effectiveness in humans. Some of the most promising are based on scientific insights gained from an unlikely source. These are commercial sex workers, prostitutes, in Kenya, shown here at a Nairobi health clinic several years ago. In Africa, where an estimated 24 million are infected with HIV, the virus that causes AIDS, it's hardly surprising that these sex workers also became infected. Yet even as millions across the continent were getting sick and dying from AIDS, for some reason this particular group remained relatively healthy. Joyce Wanjiro was one. JOYCE WANJIRO (Translated): I don't know why I am not getting it, because I have been in the business for a long time. Many of my friends have it. Some have died. SUSAN DENTZER: The reason Wanjiro and others weren't becoming ill opened up a broad new avenue of AIDS vaccine research. Dr. Seth Berkley is an AIDS vaccine activist. DR. SETH BERKLEY: When we went and looked at their blood, we found that they had very, very strong cell- mediated immune responses to HIV; that seemed to be what was protecting them. SUSAN DENTZER: In other words, the workers' blood revealed high levels of special cells that make up part of the immune system. And the cells, called "T" cells, were clearly battling back HIV. Suburban New Jersey is a long way from Kenya, but here at the laboratories of pharmaceutical giant Merck and Company, scientists are trying to produce an effective vaccine based on the clues from the African sex workers. One result is a trial vaccine that's already shown some success in holding infection in check in monkeys. Now it's in the early stages of being tested for safety in humans. The tests are part of a large research effort underway at Merck. The company previously developed vaccines for measles, mumps, rubella and hepatitis, and now the AIDS effort is the broadest vaccine research program in Merck's history. Dr. Emilio Emini heads Merck's vaccine research. DR. EMIIO EMINI: The only thing that one can do at this point to deal with this infection on a global basis is to keep it from happening, to keep uninfected people from becoming infected, and the only way to do that is to have a successful vaccine. SUSAN DENTZER: The work has required substantial advances in manipulating the human immune system to prime it for action against HIV. In effect, that system is a defense force with several branches. One branch produces antibodies, proteins that latch onto invading viruses or bacteria and block them from infecting the body's cells. Another major branch consists of the "T" cells. Those are the cells found in high levels in the Kenyan sex workers, as well as in the blood of millions of others around the world who are HIV-Positive, yet remain healthy for years. AIDS vaccine researchers at Merck and elsewhere became especially interested in one type of these "T" cells, a so- called CD-8 killer cells. DR. EMIIO EMINI: It's actually the function of the CD-8 killer cell to do exactly what the name implies. The CD-8 killer cell will then go, literally attach itself to the virus-infected cell, and kill it and thereby eliminate it from the body. SUSAN DENTZER: So the goal became making a vaccine that would prime these killers and other immune system cells for action. They'd then recognize HIV when it entered the body and be able to banish it or hold it in check. Vaccines are typically made up of either a dead version of a virus or bacteria, or a live version that's been made harmless. These trick the immune system into fighting back as if it were assaulting a real-life invader. Then so-called "memory" cells repeat that behavior when the real enemy eventually shows up. In earlier work on an AIDS vaccine, scientists had already learned that dead HIV did not produce an immune response. And giving somebody weakened version of live HIV virus was far too dangerous. Peggy Johnston is an AIDS vaccine expert at the National Institutes of Health. PEGGY JOHNSTON: So imagine trying to get a volunteer to enroll in a trial knowing what we were going to put in their arm was at one point live, infectious HIV, and that's just too much of a risk to ask an individual to take. SUSAN DENTZER: Merck scientists had to find another solution, so they settled on the idea of using only a component of HIV, literally, a single one of the virus's 12 genes. The hoped the gene would spur the immune system into producing more "T" cells. But then they had to figure out a way to get the HIV gene into the body. The solution was to insert it into another human virus, a common cold virus that had been made harmless. When injected into the body, the cold virus would carry the HIV gene to the body's cells. Since it was too risky to try out first on humans, the vaccine was first injected into macaque monkeys, like the ones shown here. They can't actually get HIV, which only infects humans, but they can contract a similar monkey version of the virus. When the monkeys were vaccinated and then exposed to that virus, they did become infected. But the virus remained at very low levels in their bodies, and the monkeys did not get sick. DR. EMILIO EMINI: And in fact, after 300 days of observation, none of the animals that had been immunized has experienced any kind of AIDS-like illnesses associated with the inoculation with the HIV-like virus. SUSAN DENTZER: With the success of the monkey experiments, several versions of the Merck vaccine are now being tested for safety in people. SPOKESPERSON: Ever participated before in an HIV or DNA vaccine trial? SPOKESPERSON: No. SUSAN DENTZER: Jan del Toro is one. She's a Colorado medical lab technician who is not HIV-positive and doesn't consider herself at risk for HIV. Nonetheless, she had her blood drawn recently week at University Hospital in Denver so she could be screened for participation in a Merck vaccine trial. JAN DEL TORO: The only way to come up with a vaccine for HIV is to volunteer, and it takes a healthy person-- you don't want sick people. And you can't... It's hard to monitor sick people, I thought, and I thought I was perfect. And I would love to be one of the people that would help get something like this on the market. SUSAN DENTZER: If these trials show that it's safe to give the vaccine to humans, the next phase of testing will determine if the vaccines are effective in preventing or lessening infection. Results are expected in 2005 at the earliest. Peggy Johnston of NIH says that Merck's is far from the only one under development. PEGGY JOHNSTON: The product that's farthest along in development, which is made by Vaxgen, called AIDSvax, is now in a phase-three study in the United States, Canada and Netherlands. And the question that this trial will answer is, does this vaccine have any efficacy in terms of being able to block HIV infection. SUSAN DENTZER: AIDSvax is designed to harness the other key branch of the immune system, the one that produces antibodies. The vaccine is made up of a protein normally found on the outer surface of HIV PEGGY JOHNSTON: It's the target for antibodies to be able to bind to and recognize the HIV virus, and hopefully stop that HIV virus from infecting new cells. SPOKESMAN: Hi, how are you doing today? CRAIG STEIN: Good. SUSAN DENTZER: Craig Stein is among the roughly 8,000 people around the world participating in the clinical trials of AIDSvax. CRAIG STEIN: I have no fear in receiving this vaccine because there's no risk at all involved in contracting the virus at all from the vaccine. I just really want to be a part of something to take that step in possibly ending this epidemic. SUSAN DENTZER: For now that's a distant dream, even with a number of other HIV vaccines also undergoing development or testing. Most experts think that that it will still be five to ten years before a safe and effective vaccine is widely available. Scientists like Emini voice hope tempered with realism. DR. EMILIO EMINI: There is just as much chance, knowing what we do not know now, all right, that we may discover something about this virus again that tells us that we're going down the wrong path. Still don't know if we're going to get there, but we'll see. SUSAN DENTZER: And although success at a vaccine would come too late to save millions, it could still halt the spread of disease even further around the world.