Merck Starts Human Trials Of Its New AIDS Vaccine
By MARK SCHOOFS
Staff Reporter of THE WALL STREET JOURNAL
Merck & Co. has initiated small human trials of a new experimental HIV vaccine that is sparking hope among AIDS scientists.
The vaccine, the result of what Merck says is the largest preclinical vaccine-research program in its history, has been able to prevent laboratory monkeys exposed to a virulent strain of HIV from getting sick, according to people familiar with the studies. Merck won't discuss details of the vaccine's progress, but confirms that it presented its data in two closed-door sessions last month, one to the AIDS Vaccine Advisory Committee of the National Institutes of Health and another to leading AIDS activists.
The company, based in Whitehouse Station, N.J., also confirms that it began testing the vaccine for safety in healthy, uninfected volunteers last week.
"After the presentation, members of the committee were excited," said Nobel laureate David Baltimore, who chairs the NIH committee. Dr. Baltimore, who is also president of the California Institute of Technology, declined to discuss the results further because of a confidentiality agreement all participants at the meeting signed.
Merck's new vaccine isn't the first to go into human trials. At least half a dozen companies are testing or have tested vaccines in people, most notably VaxGen Inc., Aventis SA, Chiron Corp. and even Merck itself. But top scientists who have seen Merck's latest animal research say that its current strategy -- which combines its new vaccine with an earlier one -- is among the most promising. And because Merck is one of the world's largest and most experienced vaccine manufacturers, its efforts attract great interest.
Researchers are particularly impressed with the thoroughness and scale of Merck's research effort, which began in the mid-1980s but shifted into high gear about four years ago. The company carried out sweeping monkey studies to winnow down a number of different vaccine candidates to the one it is now trying in humans.
"They did a beautiful, systematic job," says Douglas Richman, a leading AIDS researcher at the University of California at San Diego who heard the results at the NIH committee meeting. He also declined to elaborate because of the confidentiality pact.
Merck says it won't discuss specific results of its monkey experiments until it makes a formal presentation at a scientific forum in Colorado in April. Company researchers agreed to speak at all only because word of the vaccine is spreading quickly among members of the AIDS science and treatment community.
Merck officials say they are especially concerned that publicity will raise false hopes. The AIDS virus is "particularly insidious," says the company's chief of vaccine research, Emilio Emini. The new vaccine, he says flatly, "might fail." And even if it were to prove successful, it wouldn't be available for years.
Still, the select group of the nation's leading AIDS scientists and activists who saw Merck's research data say they are impressive. Some of these individuals, who spoke on condition of anonymity, say the experimental vaccine stopped monkeys from getting sick after they were injected with a hybrid AIDS virus containing strains that can make humans and monkeys sick. Most unvaccinated control animals, say these people, died or developed AIDS.
While Merck's new vaccine is primarily designed to prevent uninfected people from contracting HIV, the company says it also wants to test whether the vaccine can be used to treat people already infected with the AIDS virus, an experimental concept that is attracting much scientific interest.
Importantly, Merck's vaccine apparently didn't prevent the establishment of infection, what scientists call "sterilizing immunity." The animals did get infected, but they were able to control and contain the virus, say people familiar with the results. So far these vaccinated animals show no signs of disease. It isn't known how long this protection will last. Some experts fear that this approach may merely delay, rather than fully prevent, the onset of AIDS.
Still, the AIDS research community has been moving toward this "partial protection" strategy. Late last year, scientists at Harvard University, collaborating with Merck, used a different vaccine to achieve similar results -- protecting monkeys not against infection but against the development of disease. A research team from Emory University and the National Institute of Allergy and Infectious Diseases, and another team from Yale University and the Aaron Diamond AIDS Research Center in New York, recently presented similar findings with yet other approaches.
Merck's is the first of those vaccines to enter human trials, although there are plans to test the others in people, too. Wyeth Lederle Vaccines, a unit of Madison, N.J.-based American Home Products Corp., owns the rights to develop the Yale/Aaron Diamond vaccine and says it has more development work to do before it puts its product into people.
The concept of a vaccine that doesn't prevent infection but simply keeps the virus in check is controversial. But Dr. Baltimore says that, in fact, vaccines rarely if ever sterilize the body against an invading microbe. Rather, he points out, most vaccines prime the body's immune system to beat back an infection once it develops.
Most viruses, like polio or small pox, can be completely purged by a strong immune system, but a hallmark of HIV is its ability to evade even the most robust immune-system attack and lurk in the body for life. "So you can't expect a vaccine to clear the virus," says Dr. Baltimore, "because the immune system itself doesn't do that with HIV."
Yet Merck hopes that the vaccine might still be able to fully prevent infection in humans; after all, the doses of the AIDS virus used on the laboratory monkeys were much greater and more virulent than what humans are usually exposed to. Merck researchers caution, however, that this idea is speculation and still requires testing.
Even if a vaccine merely delayed the onset of AIDS, rather than preventing it entirely, many researchers believe that could still reap huge benefits. Parents in Africa, where the disease has left more than 12 million orphans, could gain more time to raise their children. And if the vaccine reduced the amount of HIV circulating in a person, it might also lower the risk of transmitting the virus, thus slowing the epidemic.
Classical vaccines work by stimulating the immune system to produce antibodies, and VaxGen of Brisbane, Calif., is in advanced stages of human testing of an AIDS vaccine designed to do that. But many experts doubt that this vaccine will succeed, since experiments suggest the antibodies it produces are unlikely to neutralize HIV. Donald Francis, president of VaxGen, says the only way to know if the vaccine works is to complete the human testing, which may be finished by the end of this year.
Merck's new experimental vaccine, like other "partial protection" vaccines, works by triggering a different part of the immune system, the so-called killer T-cells, which attack the virus by destroying cells it has already infected. It builds on an earlier experimental Merck vaccine that uses so-called "naked DNA," parts of HIV's genetic material injected directly into people, a technology Merck licensed from Vical Inc. of San Diego, Calif. But that approach stimulated relatively weak killer T-cell responses.
According to those briefed about Merck's research, the company's new vaccine hooks HIV genes onto another virus -- the adenovirus. In its natural form, the adenovirus can cause colds in people, but Merck has rendered it defective, making it incapable of causing colds or AIDS.
Harnessing this virus to carry HIV genes into cells greatly augments the amount of killer T-cells that attack HIV. But Merck is getting its best results by combining the approaches: first priming the immune system with the naked DNA vaccine and then boosting the response with the adenovirus-based vaccine. One possible complication is that people already carry antibodies to the adenovirus, which could blunt the vaccine's effectiveness.
The healthy volunteers in Merck's human study will not be exposed to the AIDS virus; the study's purpose is to see how safe the vaccine is, rather than how well it works. If Merck finds the vaccine is safe and stimulates killer T-cells in humans, it says it will put the vaccine into HIV-positive people in about four months -- one sign that it is serious about testing the vaccine for the treatment of infected people as well as the protection of uninfected ones. |
