Scientists from the Jupiter, Florida campus of The Scripps Research Institute (TSRI) have announced the creation of a novel drug candidate that is so potent and effective, that it could form the basis of an unconventional vaccine for HIV.
Scientists from more than a dozen research institutions, published their breakthrough online Wednesday ahead of print by the journal Nature.
“Our compound is the broadest and most potent entry inhibitor described so far,” said Michael Farzan, a TSRI professor who led the research. “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.”
Via Science Daily:
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 a HIV manufacturing site. The new study builds on previous discoveries by the Farzan laboratory, which show that a co-receptor called CCR5 contains unusual modifications in its critical HIV-binding region, and that proteins based on this region can be used to prevent infection.
With this knowledge, Farzan and his team developed the new drug candidate 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. “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.”
Data from the new study showed the drug candidate binds to the envelope of HIV-1 more potently than the best broadly neutralizing antibodies against the virus. Also, when macaque models were inoculated with the drug candidate, they were protected from multiple challenges by SIV.
“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.”