Sunday, August 26, 2001,
12:00 a.m. Pacific
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Scientists buoyed by series of tests for
AIDS vaccine
By Daniel Q. Haney
The Associated Press
ATLANTA — The scientists trying to create a vaccine
to prevent AIDS suddenly seem optimistic, even bullish, words not heard much in
this perennially gloomy field.
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Many researchers for the first time appear confident a vaccine is possible.
More than anything else, monkeys are responsible for the change in attitude.
Scientists for two decades have used monkeys to test theories about AIDS
treatment and prevention. But a vaccine that would safely protect a monkey from
dying of AIDS was elusive. Until now.
Now there are monkeys such as Godot, a blond, 4-year-old macaque living in
the level-2 biohazard-containment facility at the Yerkes Regional Primate
Research Center on the leafy fringes of Emory University. More than a year ago,
Godot received a big dose of SHIV, an especially nasty, lab-made amalgam of HIV
and SIV, the human and monkey versions of the AIDS virus. He ordinarily would
have been dead in six to eight months.
Anyone entering Godot's living space must dress head to toe in protective
clothing, because SHIV circulates in his bloodstream. But his curious, alert
stare at visitors peeking through a window shows he is outwardly unscathed.
Godot is infected, but otherwise healthy.
Seven months before he was infected, Godot received an experimental new AIDS
vaccine, one that experts hope will be the model for a shot to control the
worldwide epidemic.
Two other variations have been tested on monkeys at Harvard Medical School
and Merck, the U.S. drugmaker, with similar results. The Merck vaccine is in
first-stage human testing, and the Yerkes and Harvard versions should start
within six months.
Vaccine discovery has been a notoriously discouraging area of AIDS research.
But, thanks to this impressive series of monkey experiments, many researchers
have grown upbeat in the past year.
An AIDS vaccine is still no sure bet, they say. But many think they are at
least on a rational path toward finding one.
Chances of success? "Very good," predicted Harriet Robinson, who
oversaw experiments involving Godot and about 80 other monkeys. Why?
"Because of the monkeys," she said. "We are not all that
different from monkeys."
How different humans are from monkeys is key and a matter of debate among
scientists.
Still, similarities are striking. In both monkey and man, the virus destroys
its victims' cells, a crucial branch of the immune defenses. In monkeys, the
vaccine seems to blunt this attack. Maybe it will in people, too.
"Suddenly there is a sense for the first time that perhaps we have the
tools in hand today to make a substantial impact on the dynamic of the HIV
epidemic," Harvard's Norman Letvin said. "Now there is an absolute
stampede to get these technologies into humans and ask the question: Can we
translate these monkey findings into the human situation?"
Researchers hope to know soon whether these experimental shots launch the
same, early immune-system defenses seen in vaccinated monkeys. This would be an
encouraging hint of the vaccine's eventual power. Some answers could be offered
at an international AIDS vaccine conference early next month.
However, vaccine development is frustratingly slow. Even if all goes
flawlessly, Yerkes' Robinson estimated that large-scale experiments with her
vaccine won't begin until 2005. Many estimate these vaccines are still a decade
or more away.
With clear answers so far off, is all this optimism realistic?
"I ask myself whether it is justified based on the science," said
Peggy Johnston, assistant director for AIDS vaccines at the National Institute
of Allergy and Infectious Diseases. "And my conclusion is yes."
One reason is that scientists have lowered the bar. Until now, all useful
vaccines prevented infections. However, the human immune system cannot turn
back an HIV infection, and no one knows how to make a vaccine that accomplishes
something the human body cannot do for itself.
So the new vaccines are designed to accomplish the next-best thing: Train
immune defenses to hold an infection in check without preventing it entirely.
"For a long time, people assumed that the only successful vaccine would
completely prevent infection," said Robert Schooley of the University of
Colorado. "The new studies suggest that a vaccine might also have a
moderating influence on the disease process itself."
Scientists agree that blocking an infection requires the production of
powerful antibodies. This is how standard vaccines work: They show the immune
system a protein that is unique to the germ. If the bug ever enters the body,
the defenses will blaze back with antibodies that latch onto the protein,
blocking the germ and destroying it.
HIV, however, is a moving target. It mutates so rapidly that it constantly
changes proteins on its surface. So a vaccine that triggers an attack against
one strain of HIV may be powerless against another. Furthermore, the virus
covers its surface with sugar, which hides its proteins from antibodies.
Back to basics
When all of this became clear in the 1990s, scientists went back to basics.
How is it, they asked, that people often live with HIV for eight or 10 years
before falling sick with AIDS? And why do some never seem to become ill at all?
The answer turns out to be killer cells, another line of defense against
germs. Unlike antibodies, which guard against free-floating microbes, killer
cells recognize infected cells and destroy them.
HIV's favorite target is a blood cell called the helper cell. This
complicates matters enormously, since one of the helper cells' most important jobs
is nourishing and managing killer cells.
In the first days of an infection, HIV burrows into helper cells by the
billions, taking over their machinery, forcing them to build new copies of the
virus and obliterating them in the process.
Eventually, though, killer cells awaken and destroy most of the infected
cells before they can release more virus. Virus levels fall and then level off.
In the years that follow, the war is nearly a stalemate. The body produces
new helper cells almost as quickly as the virus ruins them. But their levels
gradually slide too far. At this point, virus-killing drugs can restore the
balance, but otherwise the result is AIDS and death.
New vaccines are designed to start the opening counterattack by killer cells
more quickly, so fewer helper cells become infected, and the virus eventually
plateaus at a much lower level.
"By doing relatively subtle things during the first hours to weeks of
infection, we think we can have a dramatic payoff in allowing the body's own
immune response over the long haul to contain this viral infection,"
Letvin said.
Instead of dying from AIDS, vaccinated people who become infected might live
with the virus for decades or even a lifetime.
Details of the vaccines developed by Yerkes, Harvard and Merck differ, but
all involve the same strategy: First come injections of several HIV genes,
which are taken in by muscle cells that use them as blueprints to make viral
proteins. Next comes an immune-system booster, such as a smallpox virus that
has been rebuilt to carry some of the HIV genes. The ultimate goal is still a
vaccine that will block HIV infection. Experts think a vaccine is the only
thing that will tame an epidemic that has killed 20 million people and infects
15,000 more daily.
While much of the attention is on novel strategies, a more traditional
vaccine is in final-stage testing. The AIDSVax, developed by VaxGen of
Brisbane, Calif., has been given to 7,900 volunteers in North America, Europe
and Thailand.
The vaccine is made from the outer wrapper of the AIDS virus and is intended
to trigger antibodies to prevent infection. Many AIDS experts are skeptical,
because the approach has been disappointing in monkeys, and some early
volunteers contracted HIV after being vaccinated.
Promising data
However, VaxGen's president, Donald Francis, says more promising data from
chimp experiments suggest it has as good a chance as any other approach.
Researchers will take their first look at the results in November.
Next in development is a vaccine by Aventis Pasteur of Paris. It consists of
a canarypox virus engineered to carry HIV genes, followed by a boost with
AIDSVax. The Walter Reed Army Institute of Research plans to start testing on
16,000 volunteers in Thailand next summer.
Still, a few dozen healthy monkeys such as Godot do not prove an AIDS
vaccine is on the horizon. Some in the field worry that the wish for one has
dissolved healthy scientific skepticism.
"We tend to swing from momentous lows to momentous highs in the AIDS
field," said Mark Mulligan of the University of Alabama at Birmingham.
"We may be in an Alan Greenspan time of irrational exuberance, because we
need this so desperately."
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