Protein Finding Bolsters AIDS Vaccine Hopes

It's a viral 'site of vulnerability' that doesn't mutate, scientists say.

By E.J. Mundell
HealthDay Reporter
Wednesday, February 14, 2007; 12:00 AM

Copyright © 2007 ScoutNews, LLC. All rights reserved.

WEDNESDAY, Feb. 14 (HealthDay News) -- U.S. scientists say they've spotted and mapped a tiny piece of HIV's outer coat that could be key to an effective AIDS vaccine.

Most important, this molecular target -- a portion of the virus' gp120 surface protein -- does not appear to mutate between strains, the researchers said. It also easily binds to an antibody that's already found in some humans.

The combination of those two elements had eluded AIDS researchers, until now.

"In terms of a vaccine, then, I am cautiously optimistic. I think that instead of being an impossible dream, it's now more about the technical barriers that we need to overcome to get this to work," said the study's lead author, Peter Kwong, a researcher in the Vaccines Research Center at the U.S. National Institute of Allergy and Infectious Diseases' (NIAID).

AIDS research pioneer and NIAID director Dr. Anthony Fauci agreed.

"This is a quantum leap, a big advance in what we can do now vis-a-vis the design of vaccines," he said.

The findings are published in the Feb. 15 issue of the journal Nature.

Vaccines work by pushing the body to generate immune system antibodies that recognize invading pathogens, such as viruses. However, the race for a vaccine against HIV has been particularly tough, because the organism mutates so much and constantly "shape-shifts" its outer sugary coating to elude detection.

The trick, according to Kwong, has been to find a spot that stays the same between different strains and can also be accessed by antibodies that humans could produce in large numbers.

Back in 1998, Kwong's group first captured X-ray images of the gp120 binding site, which HIV uses to hook up with CD4 immune system T-cells, the virus' prime target. The team assumed that the virus protected itself throughout the CD4-gp120 binding process by a kind of molecular-level shape-shifting on its surface, called "conformational masking."

However, closer inspection revealed a surprise. "We found that this binding actually occurs in two steps -- the first step is a kind of 'weak handshake,' or initial attachment, that's not really stable," Kwong said. "Only after that happens is there this shape-shifting change that really locks gp120 onto CD4."