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Friday, August 1, 2003
Using Herpes to Fight AIDS?
$13 Million Grant Puts New Herpes-based AIDS Vaccine on Fast Track
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"This is one of the
most innovative approaches I’ve seen in the effort to
develop an AIDS vaccine."
Michael Keefer, M.D., AIDS vaccine expert |
In an unlikely twist in the fight against AIDS, scientists have re-engineered
a herpes virus -- stripping most of its DNA and replacing it with small
snippets of DNA from the AIDS virus -- in a bid to create a new type
of AIDS vaccine.
Early tests in mice suggest that the new vaccine could help the immune
system make more infection-fighting antibodies and killer T-cells than
other vaccines, which could make it more effective. The University
of Rochester researchers who have pioneered the new approach have been
awarded a $13 million grant from the National Institute of Allergy
and Infectious Disease, a part of the National Institutes of Health
and the U.S. Department of Health and Human Services, to complete the
additional testing necessary to move the vaccine into clinical trials.
"We've known for some time that the herpes virus is a very effective
vehicle for delivering material into cells," said Howard Federoff, M.D.,
Ph.D., a University of Rochester scientist who has spent the last decade developing
the new vaccine approach. "We've recently been able to harness one
of the virus' most useful features, giving us a new tool that appears to
have strong potential as an AIDS vaccine."
That feature is a string of DNA, called an amplicon, that causes the virus' DNA
to be copied many times over before the virus infects a healthy cell. When Federoff
and his colleagues re-engineered the herpes virus for use as a vaccine, they
removed most of the herpes DNA and replaced it with snippets of DNA from the
AIDS virus. That DNA provided the instructions for making key protein molecules
that are found in the AIDS virus.
When the re-engineered herpes virus was injected into mice, healthy cells in
the mouse began making those proteins. The immune system, in turn -- recognizing
the proteins as foreign -- began producing antibodies and killer T-cells to attack
and destroy them. Should an HIV infection strike, the researchers hope that those
antibodies and killer T-cells would mount an aggressive attack against the infection
before it can take hold and cause AIDS.
Other potential AIDS vaccines have used a similar approach, but most produced
just small quantities of the desired proteins from the AIDS virus. By using the
herpes virus -- and by harnessing the DNA-copying ability of its amplicon --
the researchers have engineered the virus to deliver many times the DNA of earlier
vaccines. In their prototype AIDS vaccine, the researchers have packaged enough
DNA to produce fragments of six different proteins from the AIDS virus. The amplicon
then amplified those six DNA segments, producing 10 to 15 copies of each.
"Think of the virus as an envelope that delivers written pages," said
Stephen Dewhurst, Ph.D., a virologist who serves as co-principal investigator
for the project. "Most envelopes can deliver a few pages. This envelope
can deliver a book."
Dewhurst and his colleagues believe that the large number of DNA segments will
cause cells to produce a greater number of AIDS-virus protein fragments, and
that the immune system will, in turn, produce a larger number of antibodies and
killer T-cells. As a result, the immune system should be much better armed against
a potential HIV infection.
At the same time, the vaccine is likely to be safe. No live virus is used, and
all of the disease-causing genes from the herpes virus have been removed. The
DNA segments from the AIDS virus have been carefully selected and have been proven
not to cause AIDS.
The goal of the five-year, $13 million grant is to complete the early development
of the vaccine and prepare it for the first tests in people. Michael Keefer,
M.D., a vaccine researcher who specializes in clinical testing of AIDS vaccines,
is the principal investigator on grant. He will coordinate a team of more than
a dozen scientists working in two groups. One, led by Federoff, will work to
fine tune the re-engineered herpes virus and the packaging of its DNA payload
for use as a vaccine. William Bowers, Ph.D., a virologist and molecular biologist,
will lead an effort to ensure that the vaccine can be "scaled up" --
that is, manufactured in large quantities without quality problems that could
diminish the vaccine's effectiveness or safety. A second group, led by Dewhurst,
will test the vaccine in laboratory animals to assess its safety and effectiveness.
In particular, they will try to determine how well the vaccine spurs the immune
system to produce antibodies and killer T-cells and how long those effects last.
"Using the herpes virus amplicon is one of the most innovative approaches
I've seen in the effort to develop an AIDS vaccine," said Keefer. "It's
exciting to help move this technology forward and to see what its capabilities
are. This is cutting-edge vaccine work that may prove useful against HIV as well
as a range of other diseases."
Federoff's laboratory is also pursuing the development of amplicon vaccines
for use against several types of cancer and neurological disorders such as Alzheimer's
and Parkinson's disease. .
For more media inquries, contact:
Christopher DiFrancesco
(585) 273-4790
chris_difrancesco@urmc.rochester.edu
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