Structure of HIV-Neutralizing Antibody Solved

WASHINGTON -- A team of scientists whose leaders are funded by the National Institutes of Health has solved the structure of an antibody that is able to neutralize HIV, the virus that causes AIDS. Their work is described in the June 27, 2003 issue of Science.

The antibody, called 2G12, was isolated about a decade ago from one of the rare HIV-positive individuals whose body is able to successfully combat the virus. Scientists at the Scripps Research Institute worked with an international team to determine the 2G12 antibody structure by diffracting X-rays from crystals of 2G12.

The structure reveals an unexpected intertwining of the antibody's two chains, the extensions that grab hold of the AIDS virus. Researchers also uncovered how the 2G12 antibody neutralizes HIV by binding to sugars on the surface of the virus. The immune system usually will not attack these sugars because they are made and attached to the AIDS virus by human cells; the immune system usually accepts them as if they are part of the body.

The structure of the 2G12 antibody could provide scientists with a template to design an antigen that would trigger the body to produce 2G12. Antigens are molecules that the immune system recognizes as foreign; they stimulate the immune system to produce antibodies to combat invading microbes. The scientists believe that it might be possible to design an antigen to entice the body to produce 2G12. Such an antigen could be the basis of a vaccine against HIV.

This research was led by Ian Wilson, D. Phil., and Dennis Burton, PhD, both of the Scripps Research Institute, as well as scientists from Florida State University, the University of Oxford and the University of Agriculture in Vienna, Austria.

NIH's National Institute of General Medical Sciences supports Wilson through a program that brings together crystallographers, chemists and biologists to determine the detailed, three-dimensional structures of potential HIV drug targets.

"We are excited about the new structure solved by Ian Wilson's team," said James Cassatt, PhD, director of the NIGMS Division of Cell Biology and Biophysics. "Our program encourages scientists to look for potential HIV drug and vaccine targets using the tools of structural biology. These results show that structural biology can offer new avenues to pursue AIDS treatments and prevention."

NIGMS supports basic biomedical research that lays the foundation for advances in disease diagnosis, treatment and prevention. The institute also trains tomorrow's scientists and makes special efforts to increase the number of minority researchers. NIGMS is one of the single biggest supporters of protein structure research in the United States.

NIH's National Institute of Allergy and Infectious Diseases provides grants to Burton. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

The National Institutes of Health is part of the U.S. Department of Health and Human Services.