NIH Research Matters
February 26, 2007
Antibody Gets a Grip on HIVís Potential Weak Spot
The entire genetic blueprints of more than 2,000 human and avian influenza viruses taken from samples around the world have now been completed. The sequences will help scientists understand how influenza viruses evolve and spread, and will aid in the development of new flu vaccines, therapies and diagnostics.
Scientists have identified a tiny, unchanging region on an AIDS virus protein that may prove to be the key to neutralizing the virus. The discovery of this potential weak spot on the viral surface could have a profound impact on the development of an AIDS vaccine.
Most vaccines work by triggering the immune system to produce antibodies that help to beat back infections. But antibodies have generally been unsuccessful in defeating the human immunodeficiency virus (HIV), which causes AIDS. Among the obstacles: the proteins on the surface of HIV mutate rapidly and change shape continuously, preventing most antibodies from latching onto and neutralizing the virus.
As reported in the February 15, 2007, issue of Nature, a multi-site research team—including scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute (NCI)—decided to focus on an HIV surface protein known as gp120. HIV needs this protein to grip and gain entry to the T cells it infects. The researchers created variants of gp120 and compared how efficiently the variants interacted with the first docking point for HIV, a cell-surface molecule known as CD4. Combining these results with detailed three-dimensional pictures taken with a method called X-ray crystallography, the researchers were able to pinpoint a previously unrecognized, outer portion of gp120 that remains stable and which the virus uses to bind and infect T cells.
The researchers then took an X-ray snapshot of an antibody known as b12 interacting with gp120. The b12 antibody is one of the few known antibodies able to sense and destroy multiple strains of HIV. The antibody had previously been detected in the blood of HIV-infected patients who've successfully held the virus at bay for long periods of time. It's also been shown to help protect monkeys from becoming infected with an HIV-like virus.
The detailed structure revealed that b12 grasps onto the same unchanging region of gp120 that HIV uses to attach to the surface of T cells. The scientists concluded that the initial point of contact between HIV and T cells is also a site of viral weakness, serving as the recognition site—called an epitope—for the b12 antibody.
Dr. Gary Nabel, director of NIAID’s Vaccine Research Center and co-author of the paper, says “The structure of this gp120 epitope, and its susceptibility to attack by a broadly neutralizing antibody, shows us a critical area of vulnerability on the virus that we may be able to target with vaccines. This is certainly one of the best leads to come along in recent years.”
- AIDS Vaccines:
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NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.