February 23, 2015
New Approach To Blocking HIV Raises Hopes For AIDS Vaccine

A new compound has blocked Human Immunodeficiency Virus (HIV) infection so well in monkeys that it may be able to function as a vaccine against Acquired Immune Deficiency Syndrome (AIDS), the scientists who designed it reported Wednesday.

The novel drug candidate was developed by scientists from the Scripps Research Institute in Florida, Harvard Medical School, and more than a dozen other institutions. And it was tested in rhesus macaques, monkeys which can carry simian HIV, a virus similar to the one that infects humans.

HIV has defied more than 30 years of conventional efforts to fashion a vaccine. The new method stimulates muscle cells to produce proteins that somewhat resemble normal antibodies, which have Y-shaped heads. These proteins have both a head and a tail, and they use them to simultaneously block two sites on each "spike" that the virus uses to attach itself to a cell.

If both sites can be blocked on every spike, the virus becomes helpless and drifts off unattached into eventual oblivion by the immune system.

"It's a twofer," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which supported the work. "It's very impressive, and the method is quite promising. But it's still just in an animal model, so we'll need to see evidence of whether it works in humans."
The technique, the paper's lead author said, has now completely protected four monkeys for nearly a year against repeated attempts to infect them with large doses of several strains of SHIV, a version of HIV adapted for use in lab monkeys.

The New York Times reports that the author, Michael Farzan, an infectious disease specialist at the Scripps Research Institute, described the new compound as "the broadest and most potent entry inhibitor described so far."

It is simpler and works better, he said, than the current method that scientists are experimenting with: giving monkeys cocktails of several different antibodies that each neutralize only one or two strains of HIV, sometimes imperfectly.

The drug candidate was built on prior research works by Farzan's lab into a receptor known as CCR5, which plays a key role in allowing the A.I.D.S. virus to latch onto a cell's surface and start replicating.

The new compound of the drug binds to two sites on the virus' surface at the same time, preventing the infection of a cell.

Hailing the results of the study, Farzan said, "This is the culmination of over a decade's work on the biochemistry of how HIV enters cells. 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 now."

The study was published online by the journal Nature.