AIDS Vaccine 2001 Conference
September 6, 2001
New Vaccines May Keep HIV in Check; Remedies Don't Prevent Infection but Seem to Preserve Lab Animals' Health
The Washington Post
PHILADELPHIA, Sept. 6 -- AIDS researchers described today several experimental vaccines that don't prevent HIV infection, but apparently enable laboratory animals to live more or less healthy lives after they acquire the virus.
The vaccines, delivered by injection or, in one case, by nasal spray, work by stimulating the immune system so it can keep the AIDS virus in check. The effect has lasted for more than a year and a half, but it is not known whether it will continue indefinitely or work in people.
Such vaccines fall well short of the goal of developing a preventive HIV vaccine similar to the ones that exist for measles, mumps, tetanus and numerous other diseases. Nevertheless, they could prove useful.
"If we had a vaccine that did nothing else but contain infection, could it have an important effect on the epidemic?" asked Gary J. Nabel, head of the AIDS vaccine research center at the National Institutes of Health. "The answer is yes."
Such a vaccine would have two benefits. It would preserve the health of newly infected people. By lowering the amount of virus in the bloodstream, it would also make a person less able to transmit the infection to someone else. Reducing virus transmission would alone have a huge effect on the epidemic.
In one study, John N. Rose and Nina F. Rose of the Yale University School of Medicine, and scientists from several other institutions, used as a vaccine a weakened form of the vesicular stomatitis virus (VSV) into which pieces of AIDS virus genes had been stitched. VSV causes a nonfatal infection in livestock and occasionally infects human beings, where it causes flu-like symptoms.
The vaccine was given multiple times to seven rhesus monkeys by a combination of oral drops, intrasal drops and injections. Eight other monkeys got no vaccine. All the animals were then injected with the AIDS virus.
All became infected, and seven of the eight control monkeys developed AIDS. The vaccinated monkeys all showed a drop in CD4 cells -- a key gauge of immune system health-- but the decline was much less than that seen in the other animals. The concentration of human immunodeficiency virus in the vaccinated animals' blood was also much less. Most important, the animals have remained healthy for as long as 11 months, so far.
In a second study, Dan H. Barouch of Harvard Medical School and colleagues at several other institutions used for their vaccine a piece of DNA that encodes two genes from the AIDS virus. Along with this vaccine, they injected the animals with the gene for interleukin-2, a hormone-like substance that helps stimulate immunity. A group of control animals got no vaccine.
As before, all animals were exposed to the AIDS virus, and all became infected. Nearly two years later, three-quarters of the control animals were dead. None of the vaccinated animals was ill, and all had normal numbers of CD4 cells.
In a third study, researchers at the Yerkes Primate Research Center in Atlanta and two other places used as a vaccine a virus called vaccinia into which HIV genes had been placed. After being intentionally infected, 19 out of 20 rhesus monkeys that got a high dose of the vaccine were able to suppress the AIDS virus to below detectable levels. That's the goal for human HIV patients who are taking triple antiviral therapy.
All these vaccines work by stimulating "cell-mediated immunity," which is one of the two main arms of the immune system. The other is immunity arising from the action of antibodies, which are molecules that target microbial invaders, stick to them and allow other cells to engulf and kill them.
Molecules on the surface of viruses and bacteria stimulate the body to produce antibodies specifically designed to attack the molecules. The problem is that, for various reasons, HIV's surface molecules don't stimulate antibody production very well. The molecules are also constantly changing in small but important ways, which compounds the problem.
It's unlikely -- but not impossible -- that a preventive AIDS vaccine that doesn't force the body to make large quantities of very powerful anti-HIV antibodies can be developed. Researchers at a California biotechnology company, Maxygen Inc., described today a novel strategy for finding such a trigger.
Company scientists are cutting and splicing the genes that encode the proteins covering the surface of the AIDS virus. The technique is called "molecular breeding," or "directed molecular evolution," and it attempts to speed up what might eventually happen by chance -- the emergence of an AIDS virus whose surface proteins readily stimulate the immune system.
Such surface proteins -- or the genes for them -- might be good candidates for a vaccine that is able to stimulate antibody production.
The website for the Vaccine