Shape of rare protein reveals HIV vaccine clues
Scientists studying how the human immune system responds to HIV infection at the molecular level say they have made an important discovery that could accelerate the development of a vaccine against the virus.
The team led by Dennis Burton and Ian Wilson, from The Scripps Research Institute in La Jolla, California, United States, identified the structure of an important but rare antibody — a protein produced by the immune system to help fight infection.
The antibody, known as 4E10, is referred to as a 'broadly neutralising antibody' as it has been shown to be able to prevent nearly 100 strains of HIV isolated worldwide from attacking human cells, making it the most effective antibody against the HIV virus known to date.
Most neutralising antibodies can only block a very small percentage of HIV isolates.
Crucially, as well as determining 4E10's molecular structure, the research shed light on the structure of the 'epitope' - the part of the virus that the antibody binds to.
This could help scientists develop a 'molecular mimic' of the epitope that would stimulate the human immune system to make broadly neutralising antibodies like 4E10 against HIV, without first being exposed to the virus.
The research, published in the current issue of Immunity, was undertaken as part of the Neutralizing Antibody Consortium created in 2002 by the International Aids Vaccine Initiative (IAVI), which leads worldwide research and development of a preventive HIV vaccine.
According to Koff, the study is a powerful demonstration of how international cooperation can accelerate HIV vaccine research.
"If one looks at the total of all the independent research that has been conducted on HIV antibodies over the last 15 years, it doesn't give any means to translate the results into a vaccine," said Koff.
"The consortium has provided a mechanism to link the best laboratories with a common plan. It has allowed scientists to focus less on the groundwork and be more creative in their design of a vaccine."
He added: "The consortium has allowed intensive, comprehensive screening of a series of HIV isolates. We're able to screen candidates as they come along. This has been done through the sharing of information and, in case of an invention, the sharing of benefits."
Hermann Katinger, a co-author of the paper in Immunity, and colleagues at the Institute of Applied Microbiology in Vienna, Austria identified and isolated the 4E10 antibody 15 years ago. It was shown to be exceptionally effective at targeting an epitope in a region of gp41, an HIV protein thought to be crucial to the virus' infiltration of human cells.
Scientists working with the Neutralizing Antibody Consortium have already started developing mimics of the epitopes to which 4E10 binds, and will have to test hundreds of thousands of candidates in their search for a potential vaccine.
Reference: Immunity 22, 163 (2005)
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