10 March 2009

Vaccine for all diseases

Vaccination against everythingPyotr Smirnov, "Newspaper.
Ru»Instant immunity and universal vaccination are no longer fictions of science fiction.

Scientists have managed to develop a vaccine that stimulates the formation of "sleeping" antibodies, which are easily converted into a combat-ready state by a small additive. Depending on this additive, antibodies can react with any foreign molecule, whether it is proteins of the influenza virus, HIV or their own tumor.

Humanity has been dreaming about universal vaccination for more than a year – almost from the very moment of vaccination. Of course, you can try to get vaccinated against all infectious agents at once, but somehow you don't really want to be in the place of the immune system, which will be attacked by tens of thousands of different pathogens at once, even if they are inactivated or dead. And each vaccination has its own expiration date, depending on the strength and variability of the antigen, so you can't do without repeated injections anyway.

But if half of the responsibilities of the immune system – the recognition of foreign molecules – are assigned to scientists and doctors, then the idea of universality no longer seems so fantastic. This role was assumed by Carlos Barbas and his colleagues from the Research Institute. Ellen Scripps, who cured mice of two types of tumors at once with one vaccine and an additional injection: melanoma and colon cancer. Moreover, tumor resistance was only a demonstration of a new approach, which, according to the authors, with appropriate modification, will be suitable for HIV, influenza, and any other infections.

A multi-stage immune response can be divided into two stages: identification and destruction. And although our body has non-specific defense mechanisms, the most accurate and targeted recognition is carried out due to antibodies, without which it is simply impossible to completely remove foreign substances. On one side of each antibody, there are areas that can firmly bind to the most noticeable part of the "intruder" – the antigen. The problem is that the production of characteristic antibodies to a new pathogen takes at least a week each time. And sometimes (for example, in the case of HIV, malaria and tumors) antibodies to seemingly foreign proteins are not synthesized at all.

This is what classical vaccination is aimed at, when antigens are presented to the immune system in the most convenient and expressive form, and so-called memory cells appear that are able to produce the necessary amount of effective antibodies on demand.

The authors of the publication in PNAS proposed an alternative scheme: first they introduced a universal antigen, the "bright" part of which – "beta-diketone" – is not found in our body. As expected, after a while, antibodies appeared in the blood that could bind firmly to any molecule containing beta-diketone.

And only after that, the mice were injected with the main binding link – a molecule capable of targeting a foreign protein and at the same time containing the aforementioned beta-diketone. As a result, a chemical reaction was already taking place in the body itself to form universal antibodies with additional "appendages" introduced from the outside, specific to a specific "enemy". The tails of these antibodies triggered the necessary reactions of destruction of tumor cells with the involvement of natural killers and the complement system. It turns out that the system is absolutely ready for activation, it remains only to add a "recognizing" fragment and immune reactions are triggered. At the same time, universal antibodies circulating in the blood without the aforementioned element remain absolutely useless and harmless.

The scheme of action of "instant immunity". The universal antibodies developed in response to the vaccine first covalently bind to an adapter separately injected into the blood, selected depending on the target. Then this system binds to the target on the surface of the tumor cell, in this case, two types of integrins. And after that, the tumor cell, plastered with antibodies, is "noticed" by natural killers and the complement system (CDC). //Carlos F. Barbas /PNAS

This original and at the same time simple approach is familiar to all biologists involved in immunohistochemistry, but before Barbas, no one was able to obtain reliable clinical results using the same idea. According to the authors, who managed to partially cure (namely, cure, not vaccinate) three lines of mice from two types of tumors, the key to success in choosing a universal link – beta-diketone, which provides a covalent, and therefore much stronger connection between the antibody and the additionally injected recognizing fragment.

Optimistic scientists even plan to start work on finding "recognizing fragments" that could be taken by mouth – this would reduce the cost and speed up the procedure, not to mention the obvious benefit for those who are afraid of injections. The same method can replace the industry currently gaining momentum in the treatment of various diseases with the help of monoclonal antibodies that bind to targets of "choice" – whether they are retinal vascular growth factors in diabetics or markers of various tumors. But to do this, it is necessary to solve another, perhaps even more difficult task – to select the characteristic "recognizing links" responsible for "instant immunity".

Scientists owe part of the success of the experiment described above to these links – the molecules of integrins responsible for the contact between cells, and overexpressed on the surface of these two types of tumors. In all other cases of potential use of a universal vaccine, the only option for a "recognizing fragment" remains monoclonal antibodies specially synthesized for this purpose, which are quite suitable for self-administration.

Portal "Eternal youth" www.vechnayamolodost.ru10.03.2009

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