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$3.5 million NIH grant supports AIDS vaccine research at UC Santa Cruz
Date:9/9/2009

that emerge in the early stages of HIV infections. The studies reported in the Journal of Virology paper were led by first author Sara O'Rourke, a research specialist in biomolecular engineering at UCSC.

"We've made use of the natural variation in viral gene sequences to identify the binding sites recognized by broadly neutralizing antibodies," Berman said. "By looking at viruses from very early infections, we're seeing variations that hadn't been seen before."

One of those variations appears to change the shape of an HIV coat protein in such a way that it becomes more sensitive to neutralization by antibodies. Working with William Scott, professor of chemistry and biochemistry at UCSC, Berman's lab analyzed the effects of this genetic variant on the three-dimensional structure of the protein. The results indicate that the structural change exposes parts of the protein that are normally hidden from the immune system and are only exposed transiently during the infection process, when the viral membrane fuses with the membrane of a human cell.

In the Journal of Virology paper, the authors suggest that this novel structural variant could be exploited in designing new vaccines.

"We think that by making a vaccine based on this structure where the binding sites are exposed, it will stimulate a broadly neutralizing antibody response," Berman said. "By having the protein in a different conformation, the immune system can see those binding sites and make antibodies that would then be effective against normal virus strains during that transient window when the sites are exposed."

Studies are currently under way to examine the immunogenic potential of the variants identified in the study.

Meanwhile, the vaccine that Berman invented at Genentech in the mid-1990s, then evaluated in clinical trials at VaxGen, has been tested in a more recent clinical trial (RV 144) sponsored by U.S. and Thai government agencies. The
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Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz
Source:Eurekalert

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