Scientists compare the hunt for an AIDS vaccine to the search for the Holy Grail. And for three decades, it has proved to be about as difficult to find.
Since Robert Gallo and Luc Montagnier identified HIV — the virus that causes AIDS — in 1983, only three vaccine trials have been completed. The first failed to prevent or control infection. The second also failed, mysteriously increasing infection. The third, completed in 2009, provided protection to only about a third of the people receiving it — but how it did that is still unknown.
Yet, leaders in AIDS vaccine research say they may finally be on the cusp of a period of major discovery leading to a vaccine.
“The past few years have been a turning point,” said Gary Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. “I’m more optimistic than I’ve probably ever been in my career.”
The optimism stems from recent strides in understanding antibodies — the first weapons the human immune system deploys to fight an infection.
When a person is exposed to the AIDS virus, the immune system churns out millions of antibodies to fight it. HIV shakes off the vast majority of them, so researchers are focused on the remaining minority. These “broadly neutralizing” antibodies bind powerfully to HIV’s outer shell and prevent the virus from invading cells.
Until recently, scientists had been able to identify only four such antibodies. But in the past three years, they have worked out the structures of nearly two dozen, and they have developed the technology to find more.
If they can trigger these antibodies in healthy people, researchers suspect, they can create an effective AIDS vaccine.
A master of disguise
HIV is a master at replicating quickly — and during that process, it acquires many small mutations that create subtle changes to the contour of its shell. As a result, the immune system must play a constant game of cat-and-mouse: As soon as the body makes a new antibody to attack HIV’s outer coat, the virus has crafted a new one.
“When you’re fighting a war like this, especially with a very clever virus, it’s not going to just roll over and die when the first responder comes in. It will just put on a new mask and go on,” Nabel said.
Because the virus can mutate so easily, people with AIDS have millions of slightly different copies of HIV in their bloodstreams. With 35 million people currently infected with HIV globally, this amounts to a staggering number of viral disguises — and a successful AIDS vaccine would have to train the immune system to recognize all of them.
Nonetheless, there are vulnerable regions in HIV’s shape-shifting armor that persist across all strains, scientists say. The one garnering most interest is called “Env,” short for “envelope glycoprotein.” Resembling spikes on the virus’s surface, each Env can bind to a white blood cell called the CD4 T cell and then pull the whole virus inside. There, HIV begins its cycle of invasion, replication and escape to other white blood cells, which ravages the immune system and leads to AIDS.
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