09 July 2010

The AIDS vaccine: is it really a breakthrough?

AIDS had a thorn broken offAlexandra Borisova, "Newspaper.
Ru»Antibodies have been found to defeat 90% of known HIV strains.

The secret of the success of the fight against a multi–faceted virus is the impact on a special, unchanging site for all strains – the "spike" responsible for attaching the virus to the immune cell. Doctors are already developing a vaccine that will "teach" the human immune system to produce the antibodies necessary to fight AIDS. The secret of the success of the fight against a multi–faceted virus is the impact on a special, unchanging site for all strains – the "spike" responsible for attaching the virus to the immune cell.

Researchers from the National Institutes of Health (USA), who last year announced the creation of the first working vaccine against AIDS, announced a new sensation. If the first vaccine protected only about 30% of potential patients from the virus, then the antibodies found now promise to cope with 90% of all types of the virus. Such a quantitative increase means a qualitative change: a vaccine of such effectiveness confidently claims to be mass-produced.

The work of a large team of physicians, virologists and immunologists is published by Science: Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. (A brief description of the work is given in the press release of NIH-Led Scientists Find Antibodies that Prevent Most HIV Strains from Infecting Human Cells - VM.)

Two types of detected antibodies were able to protect human cells in vitro from infection with 90% of known HIV strains. For one of the antibodies, the mechanism of action of the protein on the virus is even shown. Scientists propose to use the obtained antibodies both in order to create a vaccine against HIV and in order to create medicines for already infected patients. In addition, the method of searching for these antibodies can be used to identify antibodies that are effective against other infectious diseases.

"The discovery of HIV antibodies of such a wide range of action and their structural analysis, explaining the reasons for their effectiveness, is a huge achievement that will push all our work to find an HIV vaccine for widespread use. The revolutionary strategy developed by our scientists to search for these antibodies can be widely applied to create vaccines against other diseases," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, where most of the work was done.

The new VRC01 and VRC02 antibodies were named after the Vaccine Research Center (VRC), in whose laboratories they were discovered. Scientists examined the blood of HIV-infected people, from where the antibodies were isolated. For the search, a special technology was used to "capture" cells that produce the necessary antibodies. The "device" used for this is an HIV protein artificially modified so that it reacts only with antibodies specific to the site where the virus attaches to the infected cell.

In vitro experiments have shown that VRC01 and VRC02 destroy a larger number of HIV strains with greater efficiency than all known antibodies to date.

The exact molecular structure of the VRC01 complex associated with HIV has been determined; it is published in a separate article (Structural Basis for Broad and Potential Neutralization of HIV-1 by Antibody VRC01). Structural data made it possible to understand how the antibody works and which part of HIV is vulnerable to it, that is, which fragment of the virus the antibody manages to attach to. Due to the fact that this time it was possible to act not "blindly", but by clearly explaining the mechanism of the antibody, doctors have already begun developing a vaccine based on these data.

The vaccine should "teach" the human body to produce sufficient quantities of antibodies similar to VRC01. Then, when infected with HIV, the immune system will be able to overcome most of the virus strains known in the world.

"We used our knowledge about the structure of the virus, in this case about the structure of the external surface of HIV, to develop molecular tools that would "highlight" its vulnerable place and lead us to antibodies that can attach to it and prevent infection of cells," explained Professor Gary Nabel, director of VRC and head of work.

It was not easy to develop a recognition mechanism: HIV strains are known for their ability to constantly change proteins on the surface to avoid recognition by the immune system. Because of this ability, there are a huge number of HIV variants in the world. Despite this, scientists have managed to localize several sites on the surface of the virus, which almost do not change from one strain to another. One of these sites – a kind of "spike" with which the virus "clings" to the cells of the immune system and affects them – is called the binding center.

The purple "flowers" on the scheme of the human immunodeficiency virus are the very thorns,
globules of three protein-polysaccharide complexes of glycoprotein 120 (gp120) – VM.

VRC01 and VRC02 block the process of introducing HIV into the cell by joining just this "spike", "rounding" it and not allowing the immune cell to "hook". This explains the effectiveness of antibodies against a wide range of strains.

The discovery of the Achilles heel of HIV, scientists hope, will help overcome the limitations that for a long time did not allow to get a full-fledged HIV vaccine that stimulates the production of the necessary antibodies.

Portal "Eternal youth" http://vechnayamolodost.ru09.07.2010

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