HIV reveals site of vulnerability; Potential vaccine target identified.
Medical researchers have found a chink in the constantly shape-shifting armour of the HIV virus. The discovery could be a significant step forward in the ongoing quest for a vaccine. The AIDS virus evades the immune system because most of the proteins that cover the surface of the virus constantly change their structure. But researchers have now identified a site that doesn't change, and shown how an antibody can bind to it. If the body could be stimulated to produce its own copies of this antibody before infection, then in theory, it would allow it to attack the otherwise elusive virus and prevent infection.
"For a long time people have been asking whether an HIV vaccine is even possible," says Peter Kwong of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who led the research. "What this finding says is that it's not just a dream — there is this site of vulnerability." The discovery hinges on an HIV protein called gp120. During infection, gp120 latches onto a protein found in the human immune system called CD4. Because this is an essential step in the virus's replication cycle, a key site within gp120 retains its conformation, unlike other HIV surface proteins.
Vaccine researchers have known about this process for years, but there was a stumbling block. Previously, they thought that this site for antibody binding was hidden within the folds of the gp120 protein until the crucial moment of infection. This masking would mean that antibodies would not be able to recognize the unchanging portion and bind to it.
But Kwong and his colleagues have now shown that is not the case. This key part of gp120 are never hidden, they found — the protein doesn't change shape until after gp120 binds with CD4. This means that the never-changing binding site is not locked away from antibodies after all.
What's more, the team has succeeded in getting an antibody, called b12, to bind to gp120, and has studied the process to reveal the structure of the two molecules as they clamp together. They report their discovery in Nature.