18 May 2009

Gene therapy vaccine against immunodeficiency virus: encouraging results

Monkeys infected with immunity to AIDS
Pyotr Smirnov, "Newspaper.Ru»An American doctor protected monkeys from AIDS by infecting them with a virus that has a gene for antibodies to the immunodeficiency virus embedded in it.

After controlled administration of a monkey analogue of HIV to animals, none of the monkeys got AIDS, and 2/3 of the group showed no signs of infection at all. If this method of prevention proves to be as effective for a person, then HIV can repeat the fate of smallpox.

Almost two hundred years of vaccination experience, even together with new advances in immunology, turned out to be practically useless at the end of the last century. The human immunodeficiency virus, due to its high variability, low immunogenicity and "competent" target selection, was able to bypass not only natural, but also laboratory barriers. During this time, hundreds of vaccines were developed, two of which even reached clinical trials, but it was not possible to achieve a good result.

All previous not very successful attempts were limited to new methods of isolation and processing of viral molecules. And even adjuvants – "enhancers" of the immune response – did not bear fruit. It is not surprising that first theorists, and then practitioners, switched to the search for fundamentally new methods, including universal vaccines, new methods of administration, in vitro vaccination followed by injection of their own "activated cells" and even gene therapy.

It was the achievements of the latter that the American Philip Johnson from the Children's Hospital of Philadelphia took advantage of. He provided monkeys with protection from acquired immunodeficiency syndrome with the help of an adenovirus encoding antibodies to the monkey immunodeficiency virus (VIO, SIV) – the monkey analogue and, possibly, the "progenitor" of HIV. In fact, the doctor infected the monkeys with HIV immunity with the help of a virus. The work of Johnson and his colleagues has been accepted for publication in Nature Medicine.

Regular injection of the antibodies themselves, both in the case of HIV and in the case of VIO, is a good way of treatment. However, this biotechnology, like a course of antiviral drugs, does not bring a cure, but only allows you to maintain the level of the virus in the blood below certain values. Due to the high cost and the need for injections in well-equipped medical institutions, such "antibody therapy" did not take root.

Regular injection of the antibodies themselves, both in the case of HIV and in the case of VIO, is a good way of treatment. However, this biotechnology, as well as a course of antiviral drugs, does not bring a cure, but only allows you to maintain the level of the virus in the blood below certain values. Due to the high cost and the need for injections in well-equipped medical institutions, such "antibody therapy" has not caught on.

Attempts have also been made to obtain a drug for a single injection: not so long ago, Ronald Mitsuyasu from the University of California in Los Angeles and his colleagues received reliable evidence of the effectiveness and safety of gene therapy in this case. In their experiment, they used an enzyme gene capable of cutting HIV RNA into separate fragments until the moment when it begins to show all its skills.

The method proposed by Johnson and his co-authors differs fundamentally. Firstly, it is a way of prevention, not treatment: the gene of antibodies to VIO is fixed in the genome of the cell once and for all. Secondly, Johnson managed to achieve more significant results: none of his nine wards developed acquired immunodeficiency syndrome, and six of them showed no signs of infection at all, including an increase in the level of virions in the blood.

The control group of six individuals, to whom the same dose of VIO was administered without prior vaccination, completely died by the end of the experiment.

It remains to be seen how long-term such a method of prevention will be. So far, it is only known that a single intramuscular injection of one of the three variants of the gene vaccine provides annual protection: during this time, all the wards managed to catch antibodies in the blood that can bind to VIO.

Whether characteristic "memory cells" are formed during such vaccination is also unknown, because in this case ordinary muscle cells, myocytes, act as cells of the immune system, into which a genetically engineered design is embedded. It is they, and not plasma cells, that produce antibodies to VIO.

The advantages of this approach include a long life of muscle cells. The disadvantages are the inability of the body to independently regulate the response, because such a function is not peculiar to them at all. Of course, they will not be able to adapt to the new versions of the volatile VIO.

In the event that Johnson's method proves effective for HIV, the latter risks repeating the fate of smallpox: mass vaccination may well eradicate the pathogen. In the meantime, you will still have to use traditional methods of protection that block the sexual transmission route.

Portal "Eternal youth" http://vechnayamolodost.ru/18.05.2009

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