— Vladimir Alekseevich, please tell us briefly about what monoclonal antibodies are?

Why are they used to create drugs?

- The use of monoclonal antibodies is a way of passive immunization of those people who do not have their own antibodies.

For example, in the case when a person has not been vaccinated and has never encountered a coronavirus before.

The introduction of a cocktail of monoclonal antibodies makes it possible to form a highly specific, highly effective virus-neutralizing response in such a person.

These are actually active substances that bind the virus and deprive it of the ability to infect the cell.

The virus that has reacted with the antibody immediately becomes “visible” to the immune system and cannot infect cells and reproduce.

And even if individual particles of the virus continue to infect cells, this process will be very limited, local, and a person will be able to fully recover and recover in a very short time.

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    N.F.

    Gamalei of the Ministry of Health of Russia

Are monoclonal antibodies a special type of antibody?

- Yes, in this case we are not talking about the plasma of people who have recovered from coronavirus or vaccinated people, which is collected for passive immunization of patients.

Sometimes, on its basis, a purified specific globulin is obtained that acts directly against the virus.

But in the case of plasma, we are talking about a polyclonal mixture of antibodies.

Monoclonal antibodies are distinguished by the fact that they react with the virus in a strictly defined place known in advance.

This is a site on the surface of the virus, for example, some site in the receptor-binding domain - the region of the virus that interacts with the receptor on the target cell.

If an antibody binds to the virus at this site, this will interfere with the interaction of the virus with the cell receptor.

Thus, you can have a panel of different monoclonal antibodies and, based on them, create a cocktail of two or three antibodies.

Antibody companies make either individual antibodies or a mixture of several antibodies - this allows you to provide broader virus neutralizing protection.

- How is the production of such drugs arranged?

- This is a pure biotechnological production, the same as, for example, the production of the Sputnik V vaccine.

To do this, special cells are grown in a bioreactor that produce monoclonal antibodies.

At the next stage, what is obtained with the help of these cells is highly purified using various stages of chromatographic purification, concentrated.

The result is a concentrated cocktail, in which there is nothing but antibodies specifically acting against the coronavirus.

Only simple substances are added - stabilizers, buffer systems.

It is a highly effective, highly purified preparation of the directly active substance.

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- The Gamaleya Center will soon receive permission from the Ministry of Health for clinical trials of a drug against coronavirus based on monoclonal antibodies.

What are the research objectives?

- It will be evaluated how reactogenic these antibodies are - any drug should be evaluated for what reactions it causes and how much it retains activity in the human body.

These are the tasks of the first and second phases of testing.

And after clinical trials, the drug will be put into practice.

— But, perhaps, already now there is a rough forecast of how this drug will work?

- Everything is clear here.

In the event that a person who is at risk of developing a severe course of the disease becomes ill with a coronavirus, antibodies are injected into him.

They block the virus, and the patient recovers very quickly - he does not develop an infectious process.

That is, this drug is not for home use, but for professional use in a clinical setting.

It should save people who are at risk for a whole list of aggravating diseases.

- What will it look like in practice?

That is, a person at risk will have to seek such special assistance from a medical institution, suspecting that he has contracted the coronavirus?

“Now all the efforts of medicine are aimed at saving people's lives.

The purpose of vaccination is to produce antibodies in a person to protect against severe illness and death.

With monoclonal antibodies, the story is the same, only they can be used more precisely.

The decision to administer the drug is made within the first days after a virus is detected in a patient, we are talking about people with diabetes, obesity, cardiovascular diseases, etc. And they do not have virus-neutralizing antibodies.

- Is there already a working name for the new drug?

- There is no name yet.

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- Do such drugs target specific strains, or are they universal?

Will the new drug help Omicron or other new coronavirus strains?

“Look, the situation here is complicated.

As I said earlier, monoclonal antibodies target specific sites, such as the S protein molecule of the virus, the binding domain receptor.

Therefore, a specific antibody used to create a drug, to some extent, retains its specificity with respect to different variants of the virus.

As a rule, the antibody cocktail is selected in such a way that it retains its activity against as many strains as possible that threaten people now or may threaten in the future.

We are lucky that our cocktail of two antibodies allows us to maintain the activity of the drug against both the old SARS-CoV-2 strain and against the Delta and Omicron strains.

This is good news, because many of the drugs that were developed for older versions of the virus have lost their effectiveness against Omicron.

- That is, such drugs can be updated for new strains of the virus, like vaccines?

“When a new variant of a virus appears, we isolate it in cell culture, and then we check to what extent the antibodies that are in our panel remain active against it.

This is standard practice.

It is possible to update such drugs, ideally you need to have the widest possible panel of virus-neutralizing antibodies, which, if necessary, can be added to these cocktails.

True, after conducting clinical trials, it is impossible to change the form of an already registered drug.

However, it is possible to make a new drug with activity against new strains.

- Given the registration and organizational issues that you mentioned, how quickly can you update a drug based on monoclonal antibodies for a new strain, if it appears?

- This issue is more likely not connected with the Ministry of Health, but with the developers.

The key point is that they have a large panel of antibodies.

If there is no such panel, then it will not be possible to quickly update the drug.

And the second point is the availability of opportunities to launch the production of a specific antibody.

And finally, the question for the Ministry of Health is how quickly a new drug can be registered.

Based on previous studies, we understand that pre-clinical trials take months, so it is very important to conduct them in advance.

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If there is a need to create drugs in advance, then you need to look for these molecules in advance, conduct preclinical studies in advance, etc. Molecules are obtained by biotechnological means: you actually clone the antibody gene into a special vector, transfer it to the producer’s cell.

The cell lives in a bioreactor, producing an antibody.

This is a very simplified description of the process.

— Drugs based on monoclonal antibodies are already being used to treat migraine, as well as Ebola.

Is it possible to identify the types of diseases for which monoclonal antibodies can be a breakthrough?

“Monoclonal antibodies are a modern technology.

They are used to treat a variety of diseases - not only infectious, but also oncological.

Antibodies can be targeted at a variety of targets in the human body - specific proteins, cell receptors.

And these drugs have a long history of use, they have been used for decades.

Now they have begun to actively use against the coronavirus.

There is a modern problem - there is also a modern solution.

All methods of struggle work in a complex - mass vaccination is needed to protect most people.

But there will also always be people who need additional treatment with monoclonal antibodies.

A vaccine does not eliminate the need to create such drugs, and vice versa.

— Now the production of monoclonal antibodies is quite an expensive and complicated process.

Approximately how much will such a medicine for coronavirus cost?

- Everything is known in comparison, but monoclonal antibodies are not a cheap therapy.

The cost can be tens of thousands of rubles.

However, such drugs are not needed by all patients, this is a means to protect people from risk groups.