The Food and Drug Administration has given a California company approval to conduct the world's first full-scale test of a vaccine to prevent infection with the AIDS virus, the company announced yesterday.
The experiment is to involve 5,000 uninfected volunteers in as many as 40 clinics in the United States and Canada and 2,500 volunteers in 16 clinics in Thailand over the next four years, the company, Vaxgen Inc. of South San Francisco, said. It said it expected to receive approval from Thai health officials and to begin testing there this year.
The announcement brought expressions of cautious hope from health officials and advocates for people with AIDS. H.I.V., the AIDS virus, has infected an estimated 30 million people, and many experts say it will take a vaccine to stop the worsening epidemic.
But scientists are sharply divided over when and which experimental vaccines to approve for full-scale testing to determine safety and effectiveness. No vaccine is 100 percent effective. Some experts favor testing any promising vaccine, even if it is likely to protect only a small proportion of recipients, arguing that something is better than nothing in a health emergency. But other experts say that full-scale tests should be conducted only when laboratory and animal research shows a solid scientific understanding of how an experimental vaccine works.
The Vaxgen vaccine was safe in tests involving 1,200 uninfected volunteers beginning in March 1992 and induced production of antibodies in more than 99 percent of the vaccinated participants, the company said. The major question the new tests aim to answer is how effective the experimental vaccine will be in protecting against development of H.I.V. among people who are exposed to the virus because of high-risk sexual practices or injection of drugs.
Advocates for people with AIDS and many scientists expressed hope that the vaccine would protect a large proportion of recipients.
"This is a watershed event in the AIDS crisis," Dr. Seth Berkley, president of the International AIDS Vaccine Initiative, a nonprofit group. But Dr. Berkley said he expected that several additional trials in developed and developing countries would be needed to test the safety and effectiveness of a number of anti-H.I.V. vaccines.
Daniel Zingale, of the AIDS Action Council, said his Washington-based group was pleased at the F.D.A. action and "cautiously hopeful."
Other scientists expressed doubts about the vaccine's prospects, saying that the earlier tests showed it boosted only one part of the immune system involving antibodies, and consequently is unlikely to protect substantial numbers of recipients. Antibodies are proteins formed to destroy invading germs in the blood.
Dr. David Baltimore, a Nobel Prize winner and head of a government advisory committee on AIDS vaccines, said that it was "unlikely that the vaccine would be totally protective." The main reason is that most experts believe an anti-H.I.V. vaccine needs to boost another part of the immune system, killer T-cells that destroy virus-infected cells, said Dr. Baltimore, president of the California Institute of Technology.
He questioned whether the trial's design could determine whether illness was less severe among those vaccinated, if they became infected with H.I.V. He called on Vaxgen to disclose the trial's scientific blueprint. Vaxgen officials did not respond to a call asking for it.
In the trial, three injections of the genetically engineered vaccine, known as Aidsvax, will be given to each volunteer over several months. The vaccine is made from part of H.I.V.'s outer coat, known as gp120, that attaches to cells to infect them. The vaccine does not cause disease because it is made from only a fragment of the virus.
The first shots are expected to be given this month in the United States. For participants, the company is recruiting gay men and the uninfected partners of people who have H.I.V. In Thailand, the participants will be uninfected injecting drug users.
The vaccine is an updated version of one made by Genentech that an advisory panel of experts rejected four years ago for Federally financed large-scale testing in the United States. The experts expressed doubts about the vaccine's effectiveness. An earlier advisory panel had recommended such tests. In accepting the second panel's recommendation, Dr. Anthony S. Fauci, the head of the National Institute of Allergy and Infectious Diseases, left the door open for a company or another country to test the vaccine.
Dr. Fauci said that he doubted that Vaxgen's vaccine would prove totally effective. "If it shows a measurable effect," then scientists would study the vaccine more intensively to determine what component was effective in hopes of using it to develop a stronger vaccine, he said.
Federal health officials are supporting research on several experimental anti-H.I.V. vaccines, he said.
The new effort is being led by Dr. Donald P. Francis, a virologist who has conducted research on hepatitis B, Ebola and other viruses. Genentech is the largest shareholder in Vaxgen, which is paying for the study. Dr. Francis, Vaxgen's president, said that for ethical reasons he tested the vaccine on himself before testing it on others. He said the company submitted its initial proposal on the AIDS vaccine in June 1997, a final version in April and received approval in May.
The new vaccine is derived from two strains of H.I.V. instead of the single strain used in the vaccine that was rejected four years ago.
The vaccine to be tested in North American is derived from two strains of H.I.V. prevalent in North America. The Thai vaccine contains formulations designed to protect against two strains prevalent there. Vaxgen
The first tests will be in Chicago, Denver, Los Angeles, Philadelphia and St. Louis. About 300 people are to participate in Denver, Dr. Franklyn N. Judson, the director of the Denver Public Health Department said.
Dr. Francis declined to name the clinics in the four other cities where tests are expected to begin this month. The tests will expand to another 10 clinics in three months. Dr. Francis also declined to name the rest of the 40 North American clinics and their locations because contracts are being negotiated. He said it will take a year to recruit participants, then three years to determine the vaccine's effectiveness.
Two-thirds of the participants in the North American tests will receive the vaccine and the rest will receive a placebo, he said.
In the Thai studies, half the group will receive the vaccine and half a placebo. The difference is to adjust for the higher rates of H.I.V. infection among the Thai participants. By comparing the number of participants who develop H.I.V. in both the vaccine and placebo groups, the researchers will be able to determine the effectiveness of the vaccine.
H.I.V. vaccine trials have an inherent conflict. For ethical reasons, researchers must continuously educate participants not to ease up on safe sex practices and other measures that can prevent infection without a vaccine. Each participant will also receive a written warning not to expect any protection from the injections because they may have received a placebo. But, if participants follow such advice, the chances of measuring the effectiveness of the vaccine are vastly reduced.
In such trials, some participants have become H.I.V.-infected before they completed all the shots.