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Genomic analysis uncovers new targets for HIV vaccine

rmacogenetics at Dukes Institute for Genome Sciences & Policy. Goldstein is the senior author of the paper.

As we expand the number of patients in future studies conducted by CHAVI researchers, we aim to discover even more polymorphisms that could provide additional clues how some patients are better able to control the virus than others, Goldstein. This should ultimately lead to novel targets for vaccines, the primary goal of CHAVI.

Two of the polymorphisms found were in genes controlling the human leukocyte antigen (HLA) system, which plays a major role in the immune system by identifying foreign invaders and tagging them for destruction.

Two of the HLA genes, known as HLA-A and B, are turned off by HIV when it enters the body, which keeps the immune system from recognizing the virus as foreign. HLA-C however is not thought to be turned off by HIV-1. The new results suggest that for some individuals at least HLA-C is involved in controlling HIV-1. Since HIV-1 appears unable to shut off HLA-C, unlike A and B, HLA-C may represent an Achilles heel of HIV, according to Goldstein, who said that a vaccine could be designed to elicit an HLA-C mediated response which HIV-1 might be unable to defuse.

This study was the first time a genome-wide approach has been used for an infectious disease, Goldstein said. Past studies have looked at individual candidate genes. Since different people respond differently to infections, a better understanding of how immune system genes control responses to infections should help us to design better treatments and more effective vaccines.

Added Haynes: CHAVI was designed to do big science, and the results of this analysis represent just the first of what should be many advances. The technology used and collaborative efforts involved were truly remarkable: together as a group we were able to do something that none of us individually could accomplish. The results of this and future CHAVI st
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Contact: Richard Merritt
Merri006@mc.duke.edu
919-660-1309
Duke University Medical Center
19-Jul-2007


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