T H E   N I H    C A T A L Y S T     M A Y  –  J U N E   2006

VRC Celebrates 5th



by Fran Pollner

VRC Director Gary Nabel
The Dawn of Creation: NIAID Director Anthony Fauci (right) traces the beginnings of the VRC to December 1996, when he and then–NIH Director Harold Varmus were invited to the Oval Office to explain HIV science to President Bill Clinton and Vice President Al Gore. The historical photo shows Fauci describing the CCR5 receptor to Clinton (right) and Gore (left), with Varmus (far left) looking on. By the end of the session, Fauci quipped, "Vice President Gore was wondering whether he had actually discovered the CCR5 receptor"—and Clinton was convinced of the need to create a center that would encompass all aspects of developing an AIDS vaccine, from basic research through vaccine production. It was five months later, in May 1997, that Clinton announced that the VRC was on the drawing board.

By the tender age of five, the VRC had launched 14 clinical vaccine trials and generated 14 clinical-grade vaccines that entailed 31 vaccine runs, one for each of the individual components of the tested vaccines.

Eight of the vaccines were anti-HIV candidates, and the other six were targeted against the likes of the Ebola, West Nile, and SARS viruses, VRC Director Gary Nabel recounted as he took stock of the VRC's accomplishments and the road ahead on the occasion of the center's fifth anniversary.http://www.niaid.nih.gov/vrc/labs_graham.htm

That disease breakdown reflects the VRC's original and continuing focus on HIV and AIDS, as well as its early, logical expansion into related emerging challenges.

The scope of VRC activities also reflects the concept behind its creation—to house in one facility the human and physical resources to develop vaccines from start to finish, from basic research to vaccine production and clinical trials, observed NIAID Director Anthony Fauci, who triggered the memories of the assembled celebrants with a bit of VRC history.

Harmonic Convergence: (left to right): VRC Director Gary Nabel; Pontiano Kaleebu, assistant director of the Uganda Virus Research Institute, Entebbe, and president of the WHO AIDS vaccine program; Barney Graham, chief, Viral Pathogenesis Laboratory and Clinical Trials Core, VRC; and Stanley Plotkin, world-renowned vaccinologist
Engineering Immunity: Two of the guest speakers—Stephen Harrison (left), Howard Hughes investigator and Harvard structural biologist, and David Baltimore, president of the California Institute of Technology in Pasadena—discussed strategies to bring neutralizing antibodies to bear against HIV, a quest VRC Director Gary Nabel called the "Holy Grail" of AIDS vaccine development

Homing in on AIDS vaccinology, Nabel discussed the details of the VRC's recent advance into Phase II clinical testing of its multigene, multiclade DNA-prime/adenovirus-boost AIDS vaccine.

The six-plasmid construct contains versions of HIV genes gag, pol, and nef, as well as three modified env genes, one from each of clades A, B, and C.

Designed to cover the major subtypes found throughout the world, the vaccine will be tested at sites in the United States, Brazil, Haiti, Jamaica, Botswana, and South Africa.*

Each component underwent testing alone and in combination in the DNA construct, in the adenovirus vector, and then in the prime-boost sequence. "The DNA-adenovirus platform proved to be an effective immunogen in humans, which we did not know before,"  Nabel said, noting that the prime-boost response is "greater than the sum of its parts." 

Eliciting broadly neutralizing antibodies remains a challenge, which is being addressed in ever more sophisticated ways, he said.

Another global priority, Fauci noted, is to develop a vaccine that would obviate the need to reconstruct the flu vaccine each year. Such a universal vaccine for seasonal, or standard, flu would also obviate the need to respond in a crisis manner to potential pandemic flu, he observed.   

*The VRC vaccine is also being tested by the International AIDS Vaccine Initiative in Phase I studies in Kenya and Rwanda and by the U.S. Military HIV Research Program in Phase I and II studies in Uganda, Kenya, and Tanzania.





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