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Duke Awarded $27 Million NIH Grant to Function as Central Testing Lab for National AIDS Vaccine Trials

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Duke Health News 919-660-1306

DURHAM, N.C. -- Duke University Medical Center has been
awarded a $27 million grant from the National Institutes of Health to
conduct the detailed analysis necessary to determine whether
potential vaccines show promise as a preventative measure
against infection by HIV, the AIDS virus.

The NIH merged two existing
federally-supported AIDS vaccine trial groups into one and
named Duke the central testing facility for the combined
entity, called the HIV Vaccine Trials Network (HVTN). The
five-year grant also will be used to attract new researchers to
the field of vaccine development.

HVTN is a combination of the AIDS Vaccine Evaluation Group
(AVEG) and the HIV Network (HIVNET). AVEG's function was to
perform Phase I and II trials of candidate vaccines on healthy
volunteers in the United States and to evaluate any immune
responses stimulated in volunteers by candidate vaccines, while
HIVNET established the infrastructure needed to carry any
candidate vaccines through Phase III trials in the nation and
abroad.

Although no federally funded vaccine has made it to Phase
III trials, Duke officials said the new organization will
streamline efforts to develop promising candidate vaccines and
shepherd them through the long testing and approval process,
and will also make it easier for new research groups to obtain
start-up funding for promising new ideas.

"The new system takes advantage of the scientific strengths
and clinical infrastructures already in place at the previous
two networks," said immunologist Dr. Kent Weinhold, principal
investigator for Duke. "The reorganization came in response to
the real need to redouble our efforts to develop and test
promising vaccines."

Weinhold emphasized that HVTN is only developing and testing
vaccines intended to keep non-infected individuals from getting
infected, and is not involved in so-called therapeutic vaccines
designed to treat patients who are already infected with
HIV.

"We are pleased that the NIH thinks Dr. Weinhold and his
colleagues at Duke University School of Medicine are the best
team to carry out these important studies," said Dr. Edward
Holmes, dean of the Duke University School of Medicine and vice
chancellor for academic affairs. "We look forward to
contributing to this critically important initiative to develop
a vaccine for AIDS."

In the early to mid-1990s, AIDS researchers were frustrated
by the lack of progress in developing an effective vaccine,
most of which were based on specific portions of HIV's protein
envelope. These "envelope subunit vaccines" ultimately proved
unable to stimulate on their own an immune system response
strong or broad enough to successfully defeat or hold the virus
in check, Weinhold said. They are, however, being tested in
combination with the next generation vaccines.

In the past few years, however, activity has picked up
dramatically as investigators have taken entirely different
approaches to building their vaccines, basing their candidates
on living non-HIV vectors, or platforms, such as canarypox
virus, Venezualan equine encephalitis (VEE) virus, cowpox virus
(vaccinia), or combinations of vaccines.

Weinhold said the challenge facing researchers is developing
a vaccine that creates in the recipient a large number of
specialized immune system cells known as cytotoxic T
lymphocytes (CTL), or killer T cells, that are effective in
killing HIV.

While the envelope subunit vaccines were ineffective in
stimulating strong CTL responses, the new generation of
vaccines are showing more promise, Weinhold said. The most
intriguing vaccine in the pipeline is based on the canarypox
virus.

Researchers insert non-infectious parts of HIV genes into
live but weakened canarypox viruses. When these viruses infect
target cells, the modified genes produce particles on the
membrane surface that trick the immune system into mounting an
immune response against HIV. The hope is that after
vaccination, these CTLs would prevent infection by killing HIV
as soon as it entered the body.

"The beauty of canarypox-based vaccines is that they infect
mammalian cells, but they don't kill them or produce new
virus," Weinhold explained. "There are no lethal side effects
to these viruses. Different trials to date have shown that when
these manipulated viruses express their antigens after
infection, they can induce CTL activity."

A vaccine based on canarypox is about to begin Phase II
testing, and if all continues successfully, Weinhold expects
the vaccine to enter Phase III trials by the end of 2001. The
vaccine would be tested on non-HIV-infected people at high risk
for being infected and would probably involve more than 12,000
patients in the United States and abroad.

Since 1991, Duke has been the central testing lab for AVEG.
During that time, Duke researchers tested all of the samples
from more than 26 different vaccine protocols involving more
than 3,500 healthy volunteers. Specifically, the labs performed
detailed assays of CTL response in more than 2,000 samples each
year, as well as broad array of other tests, such as those for
neutralizing and binding antibodies.

It was this expertise demonstrated during the life of AVEG
that led to Duke becoming the central lab for HVTN, Weinhold
said.

HVTN is being established in two phases. The first phase, of
which Duke is part, is funded at $75 million over five years
and includes the core leadership group, based at the University
of Washington, and a statistical center, based at the Fred
Hutchinson Cancer Research Center in Seattle, Wash.

NIH is expected to announce
in the near future the second phase of HVTN, which will include
all the clinical sites that will conduct the actual trials of
potential vaccines. It is expected that eight to 10 centers
will be funded. Duke did not apply to become a clinical
site.

In addition to funding the laboratory activities, the Duke
grant will allow researchers from across the country to submit
proposals for vaccine-related studies. Under the old system,
immunologists at the clinical sites could conduct
vaccine-related research using samples generated from the
trials, but experts outside the network had limited access.

"We will now have the funding to support four to five labs
across the country that have interesting or promising
proposals," Weinhold said. "This should bring into the effort
new scientific expertise and new ideas, as well as researchers
who may not have participated in vaccine research in the
past."

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