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to Section One | to Arts & Entertainment
posted Friday, February 20, 2015 - Volume 43 Issue 08
Possible HIV vaccine? Scientists create HIV-blocking molecule
Section One
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Possible HIV vaccine? Scientists create HIV-blocking molecule

by Mike Andrew - SGN Staff Writer

Scientists at The Scripps Research Institute (TSRI) have announced the creation of a new protein molecule that blocks HIV from entering host cells. The new molecule is so effective at preventing HIV infection that it might be used in the future as an HIV vaccine.

The research was published online February 18 by the journal Nature.

At present, the protein molecule is only considered a drug candidate, pending further testing, but TSRI scientists said that it 'blocks every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency virus) that has been isolated from humans or rhesus macaques, including the hardest-to-stop variants. It also protects against much-higher doses of virus than occur in most human transmission and does so for at least eight months after injection.'

Data from the new study showed the molecule binds to the envelope of HIV-1 more potently than even the most promising HIV antibodies. Also, when macaque models were inoculated with the drug candidate, they were protected from multiple challenges by SIV.

'Our compound is the broadest and most potent entry inhibitor described so far,' said Michael Farzan, a TSRI professor who led the effort. 'Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative.'

Antibodies use the body's own defenses to try to neutralize HIV, but the new compound blocks HIV from attaching to human cells and entering them.

When HIV infects a cell, it targets the CD4 lymphocyte, an integral part of the body's immune system. HIV fuses with the cell and inserts its own genetic material - in this case, single-stranded RNA - and transforms the host cell into an HIV manufacturing site.

The new study builds on previous discoveries by Farzan, who discovered that a co-receptor called CCR5 exhibits unusual characteristics in its HIV-binding region, and that proteins modeled on those characteristics can be used to prevent infection.

Based on this prior research, Farzan and his team designed the new protein molecule so that it binds to two sites on the surface of the virus simultaneously, preventing entry of HIV into the host cell.

'When antibodies try to mimic the receptor, they touch a lot of other parts of the viral envelope that HIV can change with ease,' said TSRI Research Associate Matthew Gardner, the first author of the study with Lisa M. Kattenhorn of Harvard Medical School. 'We've developed a direct mimic of the receptors without providing many avenues that the virus can use to escape, so we catch every virus thus far.'

The team also leveraged existing technology in designing a delivery vehicle. They used a small, relatively innocuous engineered virus that causes no disease. Once injected into muscle tissue, the vehicle turns those cells into 'factories' - just as HIV does - that could produce enough of the new protective protein to last for years, and maybe decades, Farzan said.

'This is the culmination of more than a decade's worth of work on the biochemistry of how HIV enters cells,' Farzan said. 'When we did our original work on CCR5, people thought it was interesting, but no one saw the therapeutic potential. That potential is starting to be realized.'

The new molecule still needs to be tested for safety when used on humans, although Fazan said he foresaw no issues in that regard.

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