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Scientists expose HIV weak spot

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lostboy:
More good news:

http://news.bbc.co.uk/2/hi/health/6357287.stm



Scientists have shown what happens when an infection-fighting antibody attacks a gap in HIV's formidable defences.

The National Institute of Allergy and Infectious Diseases-led team say the work could aid HIV vaccine development.

They have published an atomic-level image in Nature showing the antibody, b12, attacking part of a protein on surface of the virus.

HIV avoids attack by constantly mutating, but this protein segment is a weak spot because it remains stable.

   
This is certainly one of the best leads to come along in recent years
Dr Gary Nabel,
National Institute of Allergy and Infectious Diseases

Dr Elias Zerhouni, director of the US National Institutes of Health (NIH), said: "Creating an HIV vaccine is one of the great scientific challenges of our time.

"NIH researchers and their colleagues have revealed a gap in HIV's armour and have thereby opened a new avenue to meeting that challenge."

Slippery foe

Developing a vaccine for HIV has proved extremely difficult.

The virus is able to mutate rapidly to avoid detection by the immune system, and is also swathed by a near-impenetrable cloak of sugary molecules which block access by antibodies.

But certain parts of the virus must remain relatively unchanged so that it can continue to bind to and enter human cells.

A protein, gp120, that juts out from the surface of the virus and binds to receptors on host cells, is one such region, making it a target for vaccine development.

Previous analysis of the blood of people who have been able to hold HIV at bay for long periods has revealed a rare of group of antibodies - including b12 - that seem to fight HIV with a degree of success.

The latest study has revealed the detailed structure of the complex, which is formed when b12 docks with gp120.

Until now this has proved impossible, because of the flexible nature of some of the chemical bonds involved.

But the NIAID team were able to stiffen up the key protein enough to capture a picture of the complex.

They hope that revealing the structure of this bond in such precise detail will provide clues about how best to attack HIV.

Challenge ahead

Researcher Dr Gary Nabel said the work had revealed a "critical area of vulnerability on the virus".

He said: "This is certainly one of the best leads to come along in recent years."

Keith Alcorn, editor of the aidsmap.com website, said vaccines based on antibodies had so far failed to produce promising results.

"These findings are very important because they show what sort of antibodies are likely to be most successful in neutralising HIV.

"Now the challenge is to develop vaccine products that can be tested in humans."

Boo Radley:
Sounds promising! 

Let's hope this finding makes it past all the tests and trials and comes out as a potent new agent to battle HIV.

Boo

marc11864:
I just read about this in my RSS feed.

Not that a vaccine will be flying out to greet the public but this is still definitely good news.

bimazek:

this seems very very promising, with the shape, and the new facts, and the cd8 pd-1 connection, a therapudic vaccine should be possible, i hope with in 5-7 years, it is a big breakthrough
on many levels, one is the shape, another is the fact that it does not change and b12 is a vulnerability

Published online: 14 February 2007; | doi:10.1038/news070212-7
HIV reveals site of vulnerability
Potential vaccine target identified.

Medical researchers have found a chink in the constantly shape-shifting armour of the HIV virus. The discovery could be a significant step forward in the ongoing quest for a vaccine.

The AIDS virus evades the immune system because most of the proteins that cover the surface of the virus constantly change their structure. But researchers have now identified a site that doesn't change, and shown how an antibody can bind to it. If the body could be stimulated to produce its own copies of this antibody before infection, then in theory, it would allow it to attack the otherwise elusive virus and prevent infection.

"For a long time people have been asking whether an HIV vaccine is even possible," says Peter Kwong of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who led the research. "What this finding says is that it's not just a dream there is this site of vulnerability."

Hide and seek

The discovery hinges on an HIV protein called gp120. During infection, gp120 latches onto a protein found in the human immune system called CD4. Because this is an essential step in the virus's replication cycle, a key site within gp120 retains its conformation, unlike other HIV surface proteins.

Vaccine researchers have known about this process for years, but there was a stumbling block. Previously, they thought that this site for antibody binding was hidden within the folds of the gp120 protein until the crucial moment of infection. This masking would mean that antibodies would not be able to recognize the unchanging portion and bind to it.

But Kwong and his colleagues have now shown that is not the case. This key part of gp120 are never hidden, they found the protein doesn't change shape until after gp120 binds with CD4. This means that the never-changing binding site is not locked away from antibodies after all.

What's more, the team has succeeded in getting an antibody, called b12, to bind to gp120, and has studied the process to reveal the structure of the two molecules as they clamp together. They report their discovery in Nature1.

Mass production

The b12 antibody is already known to protect monkeys from infection with the related simian immunodeficiency virus. The challenge now lies in finding a way to get the human body to produce lots of b12 antibodies.

A vaccine could do this in several ways, says Kwong. It could be a protein or a string of DNA that gives the body information on how to produce b12. Or a part of the HIV gp120 protein could be used to stimulate the body to raise antibodies against it.

Some people infected with HIV have developed similar antibodies. But because they have already been exposed to the virus, it is too late to prevent permanent infection. So, such a vaccine would work only if given before infection.

The question, says Kwong, is whether a drug can be developed that stimulates antibody production in someone who has never encountered the virus. The researchers now plan animal tests to see whether high levels of the antibody can be achieved.

http://www3.niaid.nih.gov/news/newsreleases/2007/b12antibody.htm

http://scholar.google.com/scholar?hl=en&lr=&q=%22b12+antibody%22+hiv+gp120&btnG=Search

http://www.google.com/search?hl=en&q=Structural+definition+of+a+conserved+neutralization+epitope+on+HIV-1+gp120&btnG=Google+Search


Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design - group of 9
EO Saphire, PWHI Parren, R Pantophlet, MB Zwick, - 2001 - sciencemag.org
... Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1
(HIV-1) gp120 and is one of only two known antibodies against gp120 capable of ...


http://scholar.google.com/scholar?hl=en&lr=&q=%22b12+antibody%22+hiv+%22DNA%22&btnG=Search



Miss Philicia:
This sounds more promising than a lot of the "oh whatever" things one often reads... but then I've been fooled before.

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