“The test tube will be tied to the person, and he to the application”

The developers of the Sputnik V coronavirus vaccine on Thursday, August 20, began a series of briefings for Russian and foreign journalists, in which they plan to answer the main questions about the drug created in Russia. The first briefing was devoted to the platform on the basis of which Sputnik V was created – the human adenovirus. Why scientists chose him, how the vaccine was tested on animals and humans, who else in the world uses this technology and why the vaccinated will need to install the application – Lenta.ru collected the main points from the briefing.
Denis Logunov, Deputy Director for Research at the Gamaleya Research Center for Electrochemistry, Corresponding Member of the Russian Academy of Sciences, Doctor of Biological Sciences, head of the vaccine development group:
At the moment we have created two forms of vaccine. The first is a liquid, frozen vaccine that is stored at minus 20 degrees. And the second form is the freeze-dried form of the vaccine, which is stored at plus 4 degrees. Both forms of vaccine have undergone preclinical studies.
This was an extensive preclinical study involving many animal models. First, these are rodents, where safety has been studied in mice, rats and hamsters. In addition, safety studies involved rabbits, rabbit models, and two primate species. These are rhesus macaques and marmosets. The vaccine showed a high safety profile and, accordingly, was rated very well by experts from the Ministry of Health. (…)
No serious side effects have been reported. The most common side effects observed after vaccination were pain at the injection site, pyrexia (not in all volunteers), and headache. All of these adverse events were classified as minor.
In addition, as in preclinical studies, we evaluated the effectiveness of the vaccine in inducing an immune response, and here we showed that 100 percent of the volunteers who took part developed antibodies, and in a high titer – more than 1 in 15 thousand in the test for the RBD domain of coronavirus … In addition, it was shown that also 100 percent of the volunteers develop virus-neutralizing antibodies. (…)
The registration certificate has a special status – it is a registration certificate on terms. (…) What does this regulation give in the first place and why was it applied in our case? First of all, this decree allows the release of the vaccine into civilian circulation for risk groups, that is, for those people who are highly likely to get sick after the disease, either very seriously, or may even die. (…)
What does this decree oblige? In fact, it does not untie the hands on application, but, on the contrary, strongly binds them. The fact is that each tube of the vaccine will be QR-coded. Each person who will receive this drug in civilian circulation will have an application. That is, each test tube will be tied to a person, and a person to the application. As a result, the entire flow of information regarding the use of the vaccine will be collected from the regulatory authorities or at the level of regional health departments. Therefore, all vaccine use will be strictly controlled.
In addition, this conditional registration order obliges us to conduct additional extended clinical trials. And here we have now agreed on a large protocol for 40 thousand people. (…)
I will try, if I can, to explain more simply the mechanism of action of this vaccine.
The vaccine is actually a container that contains genetic material, a piece of genetic material from the coronavirus called COVID-19. Genetic material is a nucleic acid fragment of this virus that encodes a well-known protein that forms a crown, that is, a protrusion on the surface of this virus. It is the most immunogenic protein of this virus. What does immunogenic mean? Our immune system recognizes it best. Therefore, we, like all the rest of the actually researchers who create a vaccine, took this protein, and we – the gene of this protein, as a basis.
With the help of a vaccine, a fragment of this gene is introduced, on which RNA is synthesized with the help of our human enzymes. This protein is synthesized on RNA, which is incorporated into the membrane, the shell of those cells inside which the vaccine preparation is located. And as a result, the necessary protein structure is assembled on the membrane, which our immune system recognizes, producing very effective antibodies, which, upon re-infection, the possible penetration of COVID-19 into our body, will neutralize it. That is, to interact with the corona protein, thereby blocking the further penetration and reproduction of the pathogenic virus in our body.
Alexander Gintsburg, Director of the Gamaleya Research Center for Electrochemistry, Academician of the Russian Academy of Sciences, Professor:
As we know, about 10-11 days ago, a vaccine against COVID-19 was registered in the Russian Federation. After that, a lot of questions arose. They are all the same type. (…) We decided to convey to the understanding of the general public those points related to the features and advantages of the technical platform on the basis of which the vaccine was created and which will be discussed today.
As we all know perfectly well, in the national calendars of our country and in the national calendars of all countries of the world (there are about 150 national calendars), those vaccines that are included there are designed according to some well-established and well-known principles.
These are the so-called inactivated vaccines, which are obtained as a result of chemical and thermal inactivation of a virulent strain. And the resulting material is used as a vaccine. (…)
These are genetically engineered vaccines that are created using more modern methods. So, all the technological platforms I have listed now are actually not suitable for creating vaccines against RNA-containing enveloped viruses. And RNA-containing enveloped viruses are those living objects on our planet that change most rapidly. And if they change most rapidly, then, consequently, the greatest epidemiological danger should be expected from them. Which corresponds [to] what life has confirmed to us over the past decades. The main epidemiological outbreaks were just caused by RNA-containing enveloped viruses. These are usually zoonotic viruses. They live well in wild or farm animals. (…)
What is the difficulty here? The difficulty is that the surface antigens of these viruses turned out to be conformational antigens. That is, in order for our immune system to develop the necessary antibodies as a result of immunization, it is necessary to deliver the surface proteins of these viruses to the immune system in a completely native configuration, the initial one.
Figuratively speaking, the antigen must be delivered to the immune system like a crystal vase without harming this antigen in any way. And this, as it turned out, can be achieved with the help of a technology called “technology using vector carriers”, in particular adenovirus.
This technology has been developed at our institute for over 20 years.
Since 2014, when we started developing a vaccine against the Ebola virus, we decided to use this technology specifically to create a vaccine against this pathogen. What is the advantage of this technology? And its advantages are that with the help of vector-directed delivery, with the help of an adenovirus, which is obtained as a result of the fact that adenoviruses, which are our natural companions throughout our life, are removed a number of genes responsible for their replication, that is reproduction. That is, they become completely harmless. And instead of these sequences, which are artificially removed, the correct DNA sequences are inserted that encode our actual antigen. (…)
The approach we are using uses the so-called booster vaccination, the meaning of which is that the vaccine is actually injected twice with an interval of 21 days. But this introduces the same gene that encodes the same adenovirus protein. But at the same time, a different shell is used, in which this gene is immersed. If during the first vaccination the envelope of the adenovirus of the 26th serotype is used, then at the second vaccination the envelope of the adenovirus of the 5th serotype is used. This makes it possible not only to enhance the primary immune response and multiply memory cells, which are necessary for a long-term immune response, this approach allows us to avoid the immune response to the very envelope of the virus, the carrier, which in this case we do not need at all. Using this approach, as you may already know, in 2015 we created a vaccine, and in three versions, against the Ebola virus. It has been reported and used extensively against the outbreak of the disease in the Republic of Guinea. In any case, more than 2 thousand volunteers were vaccinated. (…)
This vaccine, which is being presented today, will protect those vaccinated against COVID-19 for at least two years, and maybe over a longer distance. Of course, this will require additional experiments and, accordingly, experiments.
Kirill Dmitriev, CEO of the Russian Direct Investment Fund:
We see that a number of countries are waging an information war against the Russian vaccine. We see, however, that most countries are interested in learning the facts about the Russian vaccine and, accordingly, want to understand how it works, what information is available. And today’s briefing is extremely important. And we urge not to politicize the situation around the vaccine, because we believe that many vaccines are needed. And the more vaccines there are, the better it will be for humanity. (…)
Next week, in fact, a post-registration study will begin on more than 40 thousand patients fully in accordance with international standards. This will be a randomized, double-blind, placebo-controlled clinical trial and, accordingly, this is a major study that will take place in parallel with the vaccination of risk groups. (…)
Gunzburg:
In addition to those vaccines that I have already mentioned, against the Ebola virus, a vaccine has now actually been created and the second stage of clinical trials of a vaccine against the MERS virus (Middle East Respiratory Syndrome – approx. Lenta.ru) is coming to an end. Let me remind you that this is also a coronavirus, which is 80 percent homologous to COVID-19, but with a mortality rate of up to 40 percent in fact, and the work on this vaccine against the MERS virus allowed us to create and register a vaccine against COVID-19 partly so quickly and efficiently. … (…)
Logunov:
A number of vaccines are also being created; they are now at the stage of preclinical research. They are rabies vaccine and Marburg fever vaccine. In addition, there are, of course, many projects against various pathogens, including bacterial ones, but our main hopes are connected precisely with viruses, with the antiviral application of this platform. (…)
About who this vaccine is for. It is clear that this vaccine is primarily for people who have not yet been ill. But, on the other hand, there are no restrictions on the use of this vaccine by those who have already been ill. We know that antibodies in those who have been ill disappear rather quickly, that is, immunity is not stable very often, in a sufficiently large percentage of the population, so we see no restrictions in order to vaccinate these people. Here the situation is the same as with the flu. If a person has had the flu, this is not a contraindication to get vaccinated next year or six months later.
Gunzburg:
Please note that (…) our situation is now unique. Since 1796, since the moment when Jenner invented the smallpox vaccine, as we know, vaccine preparations have never been created in the course of epidemiological processes. Especially during pandemics. (…)
Transcript provided by the organizers of the briefing.