AIDS vaccine: safe, but does it work?
The first experimental AIDS vaccine to enter human testing in the United States has caused no ill effects in volunteers up to 21 months after administration and has triggered potentially protective immune responses in some of those who received the shots, according to an analysis published this week.
The study, performed on healthy men and women deemed at low risk of acquiring AIDS, was designed to determine safety rather than efficacy, leaving scientists uncertain whether the vaccine can actually protect against the AIDS virus, HIV But the researchers express satisfaction with the trial, saying it proves they can overcome the unique challenges inherent in the design and implementation of AIDS vaccine testing.
Under the direction of the National Institute of Allergy and Infectious Diseases' AIDS Clinical Trials Network in Rockville, Md., scientists from seven U.S. universities and two private companies collaborated to test the experimental vaccine, made by MicroGeneSys inc. of West Haven, Conn. The vaccine contains a synthetic protein fragment that mimics a protein called gp160 found on the outer surface of HIV
The researchers saw no signs of toxicity in any of the volunteers, who received up to four doses of the vaccine over an 18-month period. The most sensitive blood tests showed that 30 of the 33 AIDS vaccine recipients had developed gp160-specific antibodies after the third inoculation, given six months after the initial shot.
But the antibody response appears somewhat weak. And when the researchers used a different analytical method, they confirmed the presence of gp160 antibodies in only nine individuals. Disappointingly, antibody levels dropped steadily over the next year; only four recipients retained antibodies 18 months after the first injection, as measured by the most sensitive test.
Moreover, the mere presence of antibodies provides no guarantee that a person can fend off HIV For evidence of that ability, scientists measured the antibodies' ability to "neutralize" HIV in test tubes. Only volunteers who received a fourth vaccine dose, given about 18 months into the study, showed even a hint of developing these neutralizing antibodies. By one measure, five of 24 did so, but by another measure, none did.
In a potentially worrisome finding anticipated by some researchers, blood taken f rom six vaccine recipients showed signs of "complement-mediated antibody-dependent enhancement." This poorly understood phenomenon, which may involve the production of "enhancing antibodies" in response to infection or inoculation, makes some viruses even more infectious than normal. In the case of HIV the finding has appeared so far only in test tube experiments and may not have any clinical relevance. But it warrants careful study the researchers conclude in the Jan. 15 ANNALS OF INTERNAL MEDICINE.
While the vaccine's ultimate usefulness remains unclear, the study goes a long way toward identifying and comparing the lab tests that may guide the evaluation of this and other AIDS vaccines, the researchers say. HIV's unpredictable and often long latency period has left scientists wondering how best to measure the value of candidate vaccines, especially when few recipients will likely encounter the virus during the relatively short course of a study
Perhaps most important, scientists say, the study proves the possibility of recruiting appropriate volunteers for a scientifically informative AIDS vaccine trial. To do so, researchers had to screen out applicants deemed at high risk of acquiring AIDS outside the study, since development of disease would have confounded interpretation of laboratory tests. And they had to find healthy volunteers willing to develop antibodies that would falsely suggest HIV infection on later medical exams, such as those for insurance. To explain the presence of HIV antibodies, volunteers received cards verifying their participation in the trial.