HIV vaccine gets booster

Insight on the News, Feb 17, 1997 by Peter Catalana

In 1796, Edward Jenner astonished the world by injecting cowpox into humans, which had the serendipitous effect of immunizing lucky recipients from the ravages of smallpox. Two centuries later, scientists are repeating Jenner's experiment, this time injecting a pox virus fatal to canaries into humans to prevent HIV infection. Odd as it may seem, the canary-pox vaccine is considered the best and most advanced candidate for the elusive AIDS vaccine.

According to leading AIDS researcher Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, or NIAID, the AIDS research community has a new attitude toward developing and testing an AIDS vaccine. "Vaccines are one of the areas we've responded most promptly and most emphatically to," Fauci tells Insight. "Vaccine funding projected into the next few years is certainly increasing relatively proportionally compared to other areas of AIDS research. There's no question in our budget-building process that vaccine is coming up to front and center stage." NIAID has allocated $129 million for vaccine research, up from $109 million, accounting for 8.6 percent of the entire AIDS research effort.

Noted virologist David Ho reiterated the spirit of Fauci's remarks at the Fourth Conference on Retroviruses and Opportunistic Infections recently convened in Washington. "The only real solution [for AIDS] is a vaccine," he said (see AIDS in Retreat).

Among the important results disclosed at the conference were those of Larry Corey, a medical professor at the University of Washington. Corey, who has been conducting human trials with the canary-pox vaccine and a booster called gp120, reported that 12 of 19 healthy volunteers who received four doses of the vaccine over six months had significant immunological response. When the gp120 booster was added, all 28 subjects had antibodies that blocked or "neutralized" HIV infection of new cells.

The canary-pox vaccine is a marvel of genetic engineering. The virus that kills canaries is molecularly large with many gaps in its genetic code. This allows scientists to insert HIV genes into the pox's DNA.

The altered virus then is injected into a subject's bicep, where the HIV "envelope membrane," along with critical protease and gag proteins, sprout on the surface of infected muscle cells, exposing the immune system to HIV without danger of a live virus attacking the body. Lymphocytes retain HIV's distinct signature in their immunological memories, protecting against future exposures.

Gp120 booster shots, administered nine and 12 months after the initial canary-pox vaccination, stimulate a response that prevents HIV from attaching itself to immune cells, a neutralizing effect that complements the cell-killing lymphocytes triggered by the vaccine.

Canary pox isn't the only vaccine under development. So-called "naked DNA vaccines" use human DNA injected with HIV to trigger an antigen response. "Live attenuated virus," or HIV minus certain critical genes, stimulates vigorous immune response in monkeys -- and in humans accidentally infected with defective HIV.

But the canary-pox vaccine with the gp120 booster remains the current front-runner for serious large-scale trials. "We have to look carefully at the canary-pox data and evaluate," says Fauci. "It's certainly up for serious consideration."

RELATED ARTICLE: AIDS in Retreat

The introduction of a new class of antiviral drugs called protease inhibitors has reduced dramatically the death rates from AIDS. In New York City, for example, mortality is down 30 percent from 1995, largely the result of triple-drug combinations. Does that mean a cure is at hand?

Not according to scientist at the Fourth Conference on Retroviruses and Opportunistic Infections. While viral levels can be lowered to rates undetectable through current technology, "undetectable does not mean absent," said David Ho, director of the Aaron Diamond AIDS Reseach Center in New York.

Though no major break-throughs were announced at the conference, new drugs and new combinations of drugs are constantly being tested. Expect to hear keeps drugs active in the bloodstream for longer periods. Simplifying antiviral drug regimens and reducing dosages are critical since lapses, however inadvertent, seem to be a major reason patients develop resistance to medications.

Patients who stick with their medications, however, show a significant rebound in disease fighting T-cells. This keeps opportunistic infections and debilitating illness at bay.