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Thursday, January 14, 1999 Published at 21:08 GMT


HIV vaccine breakthrough

HIV has been frozen while at its most vulnerable to the immune system

Researchers have revealed details of the first experimental Aids vaccine to produce antibodies that attack and kill the kinds of HIV found in humans.

Despite more than a decade of trials, current vaccines only tackle a few specific HIV strains which grown in the laboratory.

Professor Jack Nunberg, who led the research at the University of Montana and the Howard Hughes Medical Institute, New York, said: "Our vaccine is the first which has elicited antibodies which can neutralise any virus from human patients.

"To see that the response is very broad offers real hope that a broadly effective HIV vaccine might be developed."

David Montefiori explains the significance of the breakthrough
Professor David Montefiore, an Aids vaccine expert from the Duke University Medical Centre, North Carolina, said: "This is very exciting.

"It could be a major breakthrough for HIV vaccine development because all of the efforts to date have not been able to generate anywhere near this magnitude of antibody response. And it is vital to develop a vaccine as this is the only way to stop the spread of Aids worldwide."

The new vaccine, announced in Science magazine, was developed after researchers managed to freeze the HIV virus in the act of breaking into a cell, by using a formaldehyde solution.

To enter and infect a cell, the virus has to reveal the proteins which are most vulnerable to attack by the immune system.

[ image: A vaccine would be cheaper than the expensive drugs which fight the virus]
A vaccine would be cheaper than the expensive drugs which fight the virus
Normally these crucial proteins are only exposed for a few seconds but by freezing them open, the immune systems of experimental mice had time to develop potent antibodies to the virus. These antibodies were isolated and found to be very effective against 24 out of 25 HIV strains taken from human patients around the world.

The vaccine is currently composed of two cells - one produces the HIV virus proteins and the other wedges these in the "open" position.

However, a vaccine containing cells would be dangerous to use as the cells themselves might be attacked by the immune system. A viable vaccine would need to isolate the vital proteins from the virus.

"So the goal now is to find a way to open the virus without having the cells there," said Professor Montefiore.

"But knowing that it's going to work as a vaccine if you can do it, that will get lots of people trying - and we will eventually find a way."

More experiments needed

Professor Montefiori describes how HIV injects itself into the cells it infects
However, Professor Montefiore points out that further experiments must show the approach to work not just in mice, but also in monkeys and then humans.

"Often the antibodies you produce in mice can't be produced in humans. The next step is to test the vaccine in monkeys - if it works there it's much more likely to work in humans."

Exactly which protein produces the immune response is not yet clear. The two proteins that HIV uses to prise its way into a cell are called gp120 and gp41.

The larger protein, gp120, sits on the outside of the virus and makes first contact with the targeted cell. When it touches, it changes its shape to seize the cell in its grip.

This manoeuvre also opens the virus up, like a flower bud, revealing the gp41 protein, the equivalent to a stamen.

The gp41 protein pierces the cell wall and secures the virus's entry. The antibodies produced by the vaccine are stimulated either by the newly-shaped gp120 or by the newly-revealed gp41.

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