Vaccine Controls AIDS Virus in Early Tests on Monkeys
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Hello, everyone.
Here is an interesting article from NYTimes.com on the advances made
to developing an AIDS vaccine.
Regards,
Fatima Suleman
Information Manager
Health Systems Trust
South Africa
mailto:fatima@healthlink.org.za
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Vaccine Controls AIDS Virus in Early Tests on Monkeys
http://www.nytimes.com/2000/10/20/science/20IMMU.html
October 20, 2000
By GINA KOLATA
Using a new kind of vaccine, researchers report that they have been
able to control a particularly lethal strain of AIDS virus in mon-
keys. The vaccine, made of DNA, did not prevent the animals from be-
coming infected, but it did prevent them from becoming ill, keeping
the level of the virus so low that it was virtually undetectable in
the animals' blood.
But the researchers urged caution, saying that although they were
elated by the results, it could be a long and difficult path from
promising data in monkeys to a vaccine that worked in humans. And
even in monkeys, questions remain. It is not yet known, for example,
how long the vaccine's effects will last.
"The major point that I see in this work is the concept," said Dr.
Norman L. Letvin, who directed the work and is a professor of medi-
cine at Harvard Medical School. "It might be possible with a vaccine
to perhaps change the clinical course of an infection without block-
ing an infection."
In their study, published today in the journal Science, Dr. Letvin
and his colleagues injected eight rhesus monkeys with DNA that in-
cluded two AIDS virus genes. Since the genes were not a virus, the
vaccine itself could not transmit disease. Having inoculated the mon-
keys, the scientists then infected the animals with an AIDS virus
that would ordinarily destroy their immune systems in weeks and kill
them in a few months.
The monkeys that were given the vaccine lived for 140 days the length
of the experiment with no detectable virus in their blood, no dete-
rioration in their immune systems and no signs of ill health. Dr.
Letvin said he is continuing to monitor how long the effects last.
Eight monkeys injected with a sham vaccine and then with the virus
became ill in weeks, with high levels of the virus in their blood and
hobbled immune systems. Half were dead in 140 days.
"I think the results are very exciting," said Dr. Gary J. Nabel, the
director of the vaccine research center at the National Institutes of
Health, which paid for the study. "I think it shows for the first
time that by vaccinating in an appropriate way we can alter the
course of H.I.V. infection in terms of its ability to cause disease.
We need to be a little bit cautious in extrapolating to humans," he
added. But, he said, "by and large, this is good news."
Dr. David Baltimore, chairman of the AIDS Vaccine Research Committee
of the National Institutes of Health, an advisory committee on vac-
cine science and strategy, said the results raised hope of a practi-
cal way to battle the AIDS epidemic without the high cost and debili-
tating side effects of today's drugs.
"We can't bring drugs to all the people of the world, but you can
imagine bringing a vaccine," said Dr. Baltimore, who is also presi-
dent of the California Institute of Technology. "Another way to look
at this is that a vaccine of this sort, if it can reduce the viral
load by orders of magnitude, offers the opportunity to break the
transmission of the virus. And that's the most important thing of
all."
The hope, Dr. Baltimore and other AIDS experts said, was for a DNA
vaccine to be at least as effective in humans as a combination of
powerful AIDS drugs but without the drugs' expense or side effects.
Uninfected people who were at high risk of infection could be vacci-
nated to protect them if an infection should occur. Such a vaccine
could be especially important in developing countries where it could
not only alleviate suffering but also, by keeping the viruses in an
infected person's blood at an extremely low level, prevent the spread
of AIDS.
Dr. Robert F. Siliciano, a professor of medicine and an AIDS re-
searcher at Johns Hopkins University School of Medicine, said the
study was "a very important demonstration that immunization can
work," against AIDS. "The caveat is, Will we get the same effect in
humans? That we don't know yet. I think it's certainly possible, but
we need to do those experiments," Dr. Siliciano said.
Researchers turned to DNA vaccines for AIDS only after years of try-
ing to make traditional vaccines to elicit antibodies to the AIDS vi-
rus. Traditional vaccines are made of proteins from microorganisms
like viruses or bacteria or are made of killed or disabled microor-
ganisms. They stimulate the immune system to make antibodies, which
attach themselves to the disease-causing organisms and block them.
The problem with making such a vaccine against AIDS was that the vi-
rus had only one target for an antibody a protein that protruded from
the virus's slick fatty surface. Although vaccinated people made an-
tibodies to that protein, the antibodies were all but useless because
the virus mutated constantly, altering its surface protein and evad-
ing the antibodies.
That observation led some scientists to consider exploiting other
ways that the immune system could attack the AIDS virus. They knew
that when a monkey, or a person, was infected with an AIDS virus,
there was an initial burst of viral replication when levels of the
virus in the body shot up. Then the immune system tamps the virus
down, containing the infection often for years during which there is
no sign of illness. Finally, though, the virus breaks free, replicat-
ing wildly and causing sickness and death.
The challenge, then, was to figure out how the immune system normally
suppressed the AIDS virus and then to enhance that natural weapon.
The goal would be to make the immune system so effective that the vi-
rus would be kept at even lower levels and suppressed for even longer
times.
The key, it turned out, was the killer T-cells, also known as CD8
cells. These white blood cells attack viruses in a completely differ-
ent way than antibodies attack them. Instead of looking for the virus
itself, killer T- cells look for cells that are infected with a vi-
rus.
When a cell is infected with a virus, like the AIDS virus, it puts
fragments of viral proteins on its surface, like flags signalling
distress. Killer T- cells, cruising by in the bloodstream, are drawn
to those flags, kill the infected cells and start to proliferate into
an army that will search for other cells with the same flags and kill
them.
Over the last 15 years, scientists have steadily built a case that
killer T-cells can hold the AIDS virus in check.
They found that the cells could inhibit the AIDS virus in test tubes.
Then they found that killer T-cells proliferated in infected monkeys
and in humans at the same time as the AIDS virus replication was
brought under control. They found that the strength of an infected
individual's killer T-cell response predicted how much virus would be
in the person's blood and how well the person would do clinically.
And they found that in monkeys, when killer T-cells were obliterated,
AIDS viruses ran rampant, never coming under any sort of control and
quickly killing the animals.
Encouraged by the body of evidence, Dr. Letvin and his colleagues be-
gan looking for ways to prime monkeys to make CD8 cells. The method
that worked, they learned, was a DNA vaccine, some components of
which were provided by Merck & Company, the pharmaceutical business.
The scientists injected the animals with two AIDS virus genes along
with stimulants for cells to make an immune system hormone to speed
the production of CD8 cells. Cells picked up the DNA and used those
viral genes to make viral proteins. The proteins were harmless to the
cells, but the cells responded as they did to any foreign proteins
they put pieces of the proteins on their surfaces, signalling killer
T-cells to proliferate. The hormone amplified this process.
The result was a wave of killer cells. Ordinarily, a monkey infected
with an AIDS-like virus might end up with 5 percent to 10 percent of
its billions of CD8 cells dedicated to fighting the virus. But, Dr.
Letvin and his colleagues found, when they used their new vaccine and
then infected the monkeys with an AIDS virus, the animals would have
up to 30 percent of their CD8 cells specifically designed to fight
the infection with the virus.
So far, however, the study only shows that DNA vaccines are a promis-
ing approach in AIDS, not that this particular vaccine will protect
people, researchers emphasized.
"This is a proof of concept," Dr. Siliciano said.
Nonetheless, he and other AIDS experts said they were hopeful.
"We're not there yet in humans in terms of having a vaccine that can
do what we can do in monkeys," Dr. Letvin said. But, he added, "I
think we know how to do it."
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