News Release

Duke awarded $27 million NIH grant to function as central testing lab for national AIDS vaccine trials

Peer-Reviewed Publication

Duke University Medical Center

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."

Joining Weinhold from the division of experimental surgery are Drs. Michael Greenberg, David Montefiori and Guido Ferrari, as well as more than 25 support staff members.

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