Washington: In a major breakthrough which raises the hope for an effective AIDS vaccine, scientists have revealed the binding action of two robust antibodies that work to block the entry of the deadly HIV virus into healthy cells.
A team in the United States studied 2F5 and 4E10, the two potentially powerful antibodies against HIV, which are both rare, broadly neutralising antibodies, meaning that they can block a number of different strains of the HIV virus.
They accomplish that by binding to the "Achilles heel" of the virus -- the so-called outer coat membrane proximal region -- a part of the outer protein coating next to viral membrane that opens up and is exposed to the antibodies for a few minutes during the process of cell fusion and infection.
But the problem for infection control is that such powerful antibodies are rare in HIV infection, and current experimental vaccines have been unable to generate such antibodies. In addition, the window of opportunity for such antibodies to act is very narrow.
"Our study clearly showed that we`ve been overlooking a very important component of antibody function. The target region on the virus is only open for a few minutes -- may be 15 minutes or less.
"Unless the antibody is very close by and ready to home in on it, it won`t work. That means our goal has to be the creation of a vaccine that can induce a whole lot more of these antibodies and have them ready to go at the earliest moment of infection," lead scientist S Munir Alam of the Duke University Medical Center said.The 2F5 and 4E10 antibodies have unusually long, loopy protein segments that are hydrophobic -- the scientists found that successful docking of the antibody to the HIV outer coat membrane region required antibody attachment to HIV membrane, which contains lipid.
"This two-step mechanism, not previously appreciated, might extend to antibodies that protect against other virus," said team member Stephen Harrison of Harvard Medical School.
The team is already working on designing a vaccine that incorporates a lipid component.
"The demonstration of the role of virion lipid reactivity in the overall function of these neutralising antibodies has provided key insights into what the immune system may need to see to make such antibodies. New vaccine designs trials based on these observations are now ongoing in animals," said another team member Barton Haynes.
The study has been published in the `Proceedings of the National Academy of Sciences` journal.
Bureau Report