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Scripps research scientists devise approach that stops HIV at earliest stage of infection
Date:2/27/2008

cking to these immune system fighters, HIV manages to evades immune detection while the dendritic cells travel to the ultimate goal of the virus: immune T-Cells in the lymphoid system, which HIV then invades, setting up a deadly infection that spreads.

The second discovery is that an antibody exists that can signal immune destruction of the virus. The antibody, 2G12, protects people who have it against HIV progression, but very few of those who are infected put up such an immune reaction, said the studys first author, Sheng-Kai Wang, a graduate student in Wongs laboratory. Scientists at Scripps Research have defined the details of the action of the antibody and found that recognizes a dense cluster if sugars on one region of the viruss spiky protein coatingwhich is, strikingly, the same area that HIV uses to bind to the DC-SIGN protein on dendritic cells.

Earlier, Scripps Research Professor Dennis Burton, a co-author of this study, and Wong designed and tested synthetic constructs to mimic the clusters of sugars recognized by 2G12 that could form a vaccine. Wong invented a process he calls programmable one-pot synthesis that allows him to quickly assemble many types of carbohydrate structures by placing a large number of chemical building blocks into a reaction vessel to make sequential chemical reactions.

So the Scripps Research team built a dendron structure that can bind to the DC-SIGN protein, preventing HIV from doing so, and which also mimics the sugar clusters that 2G12 binds to, prompting the immune system to produce destructive antibodies to the viral coat. The sugar structure is able to inhibit HIV from binding to DC-SIGN on dendritic cells in vitro," Wong said. "But to become a vaccine, as tested in mice, the sugar structure has to be attached to a carrier as the sugar structure alone is too small and too weak to be used as a vaccine. The sugar-carrier conjugate will also inhibit HIV from binding to DC-SIGN.

The resea
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Contact: Mika Benedyk
mbenedyk@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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