Over the past 15 years, scientists have come to know more about HIV than any other virus. But they haven't been able to break the chain of transmission with a vaccine — the only surefire way to stop the spread of the disease.
An effective AIDS vaccine would train the immune system to fight off the HIV infection by giving it a taste of the deadly invader. This would give the body a kind of immunological “head start” by priming it to attack the virus as soon as it appears instead of taking time to marshal a defense.
But vaccine development is a difficult, time-consuming task, mainly because scientists have a relatively poor understanding of just how HIV and the immune system interact. The scientists are still unsure exactly how to stimulate the body's disease-fighting cells and what cellular material to use to do the stimulating.
“We believe that, in the next nine years, we will have a vaccine that will have some impact,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Md. “We may not hit a home run right away; it's an iterative process. But I think we'll see the first round of some measurable success.”
Four years ago, Fauci's institute declined to fund trials on AIDS vaccines because administrators deemed none promising enough to justify the expense. But President Clinton's 1997 challenge to scientists to develop an AIDS vaccine by 2007 and new research developments have led to a change of heart. The NIAID is participating in upcoming trials of a vaccine it rejected four years ago called gp120, which consists of genetically engineered fragments of HIV's outer coat.
The trials will be the first large-scale test of an AIDS vaccine. The U.S. Food and Drug Administration in June approved a version of gp120 called Aidsvax, manufactured by VaxGen of South San Francisco, Calif., for testing on 5,000 volunteers in the United States and 2,500 more in Thailand. The trials will take at least three years. Earlier small-scale trials showed the vaccine built up some measurable viral resistance in more than 90 percent of patients who received the product.
The gp120 vaccine works by stimulating a so-called humoral response, in which the immune system smothers the invader with antibodies before it can infiltrate healthy cells. The advantages are that gp120 is safe and relatively simple to prepare. The problem is that antibodies produced in response to the vaccine's genetically engineered HIV fragments often fail to recognize active HIV when the “wild” virus turns up in patients.
Another approach is to use vaccines to prompt a second kind of reaction, known as a cellular response. This usually involves implanting HIV genes in non-HIV viruses, spurring disease-fighting cells to kill the HIV-infected cells. These vaccines are more complicated to prepare and, to date, have prompted only modest immune responses. Some researchers also worry that integrating HIV genes into human cells could harm patients.
Several combination vaccines are in early trials. One would use live canarypox virus loaded with HIV genes, followed by a booster shot of gp120. But the vaccines again are complicated to prepare, and the virus could potentially cause disease.
“It is unlikely that we will develop a vaccine suitable for wide-scale use in humans within the next five years,” David Baltimore, president of the California Institute of Technology and chairman of NIH's Vaccine Research Committee, wrote recently in Scientific American. “But there is hope . . . even a partially effective vaccine could be valuable in limiting the amount of virus in patients, thus potentially reducing their infectiousness and the symptoms they suffer.”