01 December 2011

A gift for AIDS Day

A "genetic vaccine" against the AIDS virus has been createdKirill Stasevich, Compulenta
The DNA of antibodies effective against most forms of HIV is sewn into the DNA of muscle cells, and muscle cells begin to synthesize these antibodies, ignoring mutations that change the appearance of the virus.

About 2 million people get AIDS every year – and for about thirty years scientists have been trying to create an effective vaccine against its causative agent. The usual approach, in which a set of fragments of an inactivated virus is used to stimulate immunity, has not justified itself. HIV easily changes its own external signs, becoming unrecognizable to the immune system. It took scientists some time to find a molecule in the virus that would excite at least a moderate immune response, but did it for all mutant varieties of HIV.

To make the body constantly produce antibodies to this universal trait, researchers from the California Institute of Technology (USA) proposed using genetic engineering methods. The DNA encoding the antibodies was sewn into a modified adenovirus, which could enter cells, embed its DNA into the genome of the cell, but could not reproduce. This adenovirus with antibody DNA was injected into the muscles of mice. The DNA was embedded in the cellular DNA, after which the muscle cells began to produce antibodies against the AIDS virus.


Crystal structure of modified adenovirus,
used to deliver DNA antibodies to muscle cells
(drawing by the authors of the study).

Before that, the researchers tested several types of human antibodies for their effectiveness against HIV; as a result, two types of immunoglobulins were selected: they protected the mouse, even if the concentration of the virus was 100 times higher than it happens with a normal infection. The immune system of the mice was, of course, "humanized" so as not to conflict with the injected antibodies. 52 weeks after a single injection of adenovirus with antibody DNA, animal muscle cells continued to successfully synthesize antibodies.

The results of the experiments were published by scientists in the journal Nature (Balazs et al., Antibody-based protection against HIV infection by vectored immunoprophylaxis). It cannot be said that the authors are absolute innovators: a similar technique was successfully used a couple of years ago, trying to experimentally limit the spread of the monkey immunodeficiency virus. In this case, the most impressive thing is how long-lasting such a "genetic vaccine" turns out to be.

And, of course, it is important that this method works on the whole organism, and not in cell culture, and with human HIV. Muscle cells will produce antibodies against the virus, ignoring its tricks with mutations and "disguises".

On the other hand, there is a standard objection that mice and monkeys are not people after all, and it is not entirely clear how everything will happen in the human body. It is believed that the usual systematic administration of antibodies is unjustified in terms of the "cost –effectiveness" ratio. However, the most confusing thing about the proposed method is that the production of antibodies cannot be stopped: whether there is an AIDS virus, muscle cells will still produce antibodies against it. Perhaps this will not affect the body in any way, or maybe vice versa. Anyway, it would be nice to create some kind of genetic "switch" for the synthesis of antibodies against HIV, if they are not needed.

Prepared based on the materials of the California Institute of Technology: Biologists Deliver Neutralizing Antibodies that Protect Against HIV Infection in Mice.

Portal "Eternal youth" http://vechnayamolodost.ru
01.12.2011

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