Subject: Testing an AIDS Vaccine in People May Be Tougher Than Creating It Date: Published: 4/14/86 154 lines Source: Wall Street Journal. Copyright Dow Jones & Co. Inc. Testing an AIDS Vaccine in People May Be Tougher Than Creating It --- By Michael Waldholz and Jerry E. Bishop Staff Reporters of The Wall Street Journal Although development of a long-sought AIDS vaccine seems near, testing in humans would probably take at least three years, and maybe as many as eight. "It may be that the lab work will be the quickest part of developing a vaccine," says David J. Sencer, a Boston public health consultant who was New York City's health commissioner when the AIDS epidemic first struck. Among the unprecedented problems: recruiting hundreds or even thousands of suitable volunteers and monitoring them for the years it will take to be sure the vaccine is both effective and harmless. In addition, "the sociological problems (of testing) are going to be horrendous," says Dr. Sencer. For instance, he says, the inoculated volunteers will produce antibodies to the virus and become "positive" for any AIDS blood test, a development that may threaten their ability to get jobs or insurance. From the moment two years ago when American and French scientists discovered the virus causing AIDS, or acquired immune deficiency syndrome, public health officials have been convinced that only a vaccine can stop the AIDS epidemic. Vaccines work by tricking the body's immune system into acting as though it had been invaded by a disease-causing virus. The immune system launches a counterattack of antibodies, small bits of protein that can render a virus harmless. The antibodies produced by the vaccine then circulate in the blood for years, protecting against future invasions. Last month, scientists at Harvard and in France announced that they had found a natural virus in Africa that was closely related to the human AIDS virus but didn't seem to cause disease. Moreover, researchers at Genentech Inc., the San Francisco biotechnology company, used genetic engineering techniques to make synthetic copies of a protein from the AIDS virus that also stimulates antibodies. And, last week, two teams of American virologists said they had inserted genes from the AIDS virus into vaccinia virus, which when administered to animals stimulated AIDS antibodies. The vaccinia virus has been used for decades as a smallpox vaccine, although it hasn't been used in the U. S. since 1970, when the disease was eradicated. Robert Nowinski, president of Genetic Systems Inc., the Seattle-based unit of Bristol-Myers Co. that helped develop the vaccine, is so enthusiastic about this approach that he predicts he'll be ready to ask the U. S. Food and Drug Administration for approval to begin human testing by year's end. Still, "there's no way to know its effectiveness until trials are done in humans." But formidable obstacles face such tests. Ordinarily to test a vaccine, public health researchers recruit volunteers from among those who are likely to get the disease. Half the volunteers are vaccinated and half serve as an unvaccinated "control" group. If the disease is the type that hits in sudden epidemics, the effectiveness of the vaccine in preventing disease is apparent quickly. When the Salk polio vaccine was tested in the mid 1950s, its effect in blocking summertime outbreaks was immediately clear. AIDS is different, researchers say. Instead of sudden polio-like outbreaks, AIDS is spreading steadily and relentlessly among homosexual men and drug addicts. Most of those exposed won't become ill until months or even years after being infected. Thus, any test of the vaccine's ability to prevent disease must follow test subjects for years. Moreover, researchers won't easily find "an appropriate volunteer population," notes Kenneth Berns, chairman of microbiology at Cornell Medical College in New York. Most homosexual men, especially the more promiscuous ones at the highest risk of developing AIDS, have already been exposed to the AIDS virus and thus can't be test subjects even though they may not yet have AIDS. Drug addicts, being involved in an illegal activity, are unlikely volunteers. Thus, it may take months or even a year or two to find sufficient numbers of volunteers who are both free of previous exposure to the AIDS virus but are in danger of such exposure. One researcher estimates that, even if sufficient volunteers can be found, the disease's long latency period means it would take as long as four years to find out if the vaccine prevents AIDS. As a result, vaccine researchers like Stanley Plotkin of the Wistar Institute in Philadelphia note that researchers will have to settle for determining if the vaccine prevents infection by the virus rather than whether it prevents AIDS. Antibody tests can tell whether, after vaccination, the volunteers were infected by the AIDS virus. But this shortcut, which might reduce testing by two years, is expected to be controversial. Vaccine developers will have to convince other scientists as well as the FDA that the antibodies raised by the vaccine will prevent the ultimate development of AIDS. Whether the government is willing to undertake the enormous immunization program with this sort of evidence is uncertain. A bigger obstacle may result from the fact that once volunteers are located "you're ethically bound to do what you can to educate them about avoiding practices that put them at risk of AIDS," explains William S. Jordan, director of microbiology and infectious diseases at the federal National Institute of Allergies and Infectious Diseases. Persuading vaccinated and unvaccinated volunteers to avoid exposure to the AIDS virus is contrary to the scientific needs of the test. In order to get statistically significant differences between the two groups, a minimum number of volunteers have to be exposed to the virus. So the more the volunteers avoid exposure the greater the number that will have to be recruited for the test and the longer it will take to obtain statistically significant results. This problem could add months to the trial. Scientists also are uneasy about the potential AIDS vaccines under development in the laboratory. The AIDS virus belongs to a family of viruses capable of causing cancer in some people. Using a whole virus, such as the seemingly innocuous AIDS-related virus recently discovered in Africa, raises worries whether the vaccine would cause cancer. The more likely possibility of a vaccine made with a genetically engineered vaccinia virus is also worrisome, say researchers. Vaccination against smallpox with the vaccinia virus ended in 1970 because risks of adverse effects of the vaccination outweighed the then-negligible risks of contracting smallpox. "Using the vaccinia virus to produce AIDS antibodies is an elegant research tool but has very serious public health problems," says Edwin Kilbourne, chairman of the microbiology department at Mount Sinai medical school in New York. The people that suffered adverse reactions to smallpox vaccination were those with immune defects similar to the immune defects seen in AIDS. Thus, vaccination with the virus in persons who've already been exposed to the AIDS virus, but haven't yet developed AIDS, may pose a greater risk than the risk of developing AIDS, Dr. Kilbourne speculates. Even if an AIDS vaccine is found that is effective, public health officials will face the ultimate question of who to vaccinate. Since the vast majority of the population is neither homosexual nor addicted to intravenous drugs, vaccination on the scale used against polio or measles would be neither practical nor acceptable. Vaccination of only those homosexual men or drug addicts would be effective only if they were vaccinated before they indulged in practices that exposed them to the AIDS virus, suggesting that potential homosexuals and addicts would have to be identified at an early age. (This article is made available here by Dow Jones Co. for the personal and non-commercial use of callers to this bbs, in the hope that it will be of some help to those who are suffering from the disease and others who are seeking to help them.)