Anatoly Altshtein: "The use of" EpiVacCorona "must be stopped before the checking"

Yelena Ivanova, Natalia Seibil

- A dozen vaccines against COVID-19 are used in the world. How do they differ from each other?

- When the pandemic struck, vaccines began to be developed in many countries. All vaccines have been developed from platforms that have been well studied in previous years. A platform refers to a set of approaches and methods that can be used to make a modern vaccine. Some of these platforms have not yet been used for actual vaccines.

In the world, including in Russia, a fairly good platform has been created over the past decades, which was based on obtaining vaccines using viral vectors. Since the eighties, work has been carried out on the use of adenovirus as a vector, there have been many scientific developments allowing the use of such vector platforms for gene therapy and vaccine production. If an established platform, which has already been studied, is used, then the necessary development can be performed quickly enough, as was demonstrated when creating coronavirus vaccines in Russia and in a number of countries (China, USA, Great Britain, Germany, etc.).

- What is a vector platform?

- A certain safe virus is taken, which can multiply well and which can be obtained in sufficiently large quantities. The necessary gene of the pathogen against which it is necessary to immunize is inserted into the genome of this virus. In particular, this approach was applied at the N.F. Gamaleya center by a team of authors (A.L. Gintsburg, B.S. Naroditsky, D.Yu. Logunov and others) in order to create a vaccine against the Ebola virus and against the MERS coronavirus. When the hard times of the coronavirus pandemic came, SIC specialists made the appropriate vaccine (Sputnik V) against the modern coronavirus -SARS-CoV-2.

- Now there are three domestic vaccines in civil circulation. You told about "Sputnik". What about the other two?

- We have a number of institutions that have their own proven platforms, with the help of which it is possible to create vaccines against coronavirus infection. In particular, in addition to the Sputnik V vector vaccine, two more vaccines have been developed. This is a vaccine based on an inactivated virus (whole virion vaccine) KoviVac and a vaccine based on viral peptides - EpiVacCorona.

As for the whole-virion vaccine, it is being developed by the Chumakov Research Center. In the early 1950s. Jonas Salk (USA) created an inactivated whole-virion vaccine against poliomyelitis. Such a vaccine was produced at the Institute of Poliomyelitis and Viral Encephalitis (the predecessor of the M.P. Chumakov Research Center) in 1956-1958, then it was replaced by a live polio vaccine, which was developed in the USA by Albert Sabin.

The great merit in the creation of this vaccine belongs to the Poliomyelitis Institute, which set up production and managed to introduce it into real practice. The Chumakov Research Center has a historical experience in the production of whole-virion vaccines. They also produce an inactivated whole-virion vaccine against tick-borne encephalitis, and have also worked out the production of an inactivated vaccine from weakened variants of the polio virus. A vaccine against the new coronavirus is now being developed on the same platform. The same vaccines are produced in a number of countries (China, India, etc.). They have shown their certain effectiveness. Thus, although the third phase of clinical trials has not yet been completed, the CoviVac vaccine of the M.P. Chumakova promises to be effective.

The third vaccine, created in Russia and registered in October 2020, is the so-called "peptide" vaccine. It is also created on a platform that has its own history. Experiments have shown that this kind of vaccine can be made, can work. But so far there is not a single effective vaccine that is widely used in medical practice.

- What is the difference between peptide vaccines?

- Peptide vaccines are made on the following principle. Each virus has proteins that contribute to the development of immunity against this virus. In coronavirus, this is a surface protein called S-protein. When developing peptide vaccines, an analysis is done, which shows that there are certain areas in the protein, the response to which, during immunization, leads to the appearance of neutralizing antibodies, which are involved in protecting the body from viral infection. Neutralizing antibodies are antibodies that can bind a virus and prevent it from entering cells. The surface protein of the coronavirus has been analyzed. A number of sites were found there, which are called epitopes. A set of antibodies can arise against the same protein in response to these different regions.

The principle of peptide vaccines is as follows: instead of taking a whole protein, they take parts of this protein, peptides. Peptides are chains of amino acids. Chemically, knowing the order of these amino acids, you can synthesize these peptides. They then attach to a neutral protein. That is, they are not immunized with all protein, but only with those sites that are responsible for the production of neutralizing antibodies. A number of antiviral vaccines have been developed on this principle. But I must say that there are no good vaccines developed according to this method that would go into medical practice. Nevertheless, it can be expected that a sufficiently effective vaccine can also be made on the basis of this principle.

The specialists of the Research and Development Center "Vector" took such a difficult path. They isolated several regions in the coronavirus protein S, synthesized the corresponding peptides, and combined these peptides with the internal N-protein of the virus, obtained by a genetically engineered method. As a result of this approach, they received a drug that, in theory, should immunize against coronavirus. But it is impossible to guarantee that these peptides, obtained chemically, will cause the synthesis of the correct antibodies in the body and protection from infection, it requires a very thorough research.

- Did something go wrong in the end?

- The drug was made and passed the first and second phases of clinical trials. In October-November, the third phase of clinical trials of this drug was started. The drug is quite safe. There is no doubt about it. But when several thousand people were vaccinated as part of the third phase, many of these people began to turn to firms that test antibodies. And to their surprise, they saw that there were no antibodies. They turned to firms that can determine antibodies to the S-protein - the main protein responsible for immunization to the virus. A community of people vaccinated with the EpiVacCorona vaccine has emerged. There are several hundred of them. They turned to the manufacturers with the question "What's the matter?" and received the answer that antibodies to the S-protein cannot be detected in this way, since there are about 12 determinants in the S protein, and only three are included in the vaccine, and conventional methods that detect antibodies in this case are not suitable. This statement was made officially. And only the system that is made in our country is suitable, they said in "Vektor".

- How is this test system different?

- Its exact composition has not been published. However, according to the available data, one might think that this system is built on the basis of the same components from which the vaccine is made. This should include three peptides and the internal antigen of the coronavirus, on which these peptides are implanted. In addition, during genetic engineering manipulations, there is another additional bacterial protein, which is also included in this vaccine.

- How is the detection of antibodies done by modern immunological methods?

- The most accepted method is enzyme immunoassay. In order to conduct research with this assay, those proteins against which antibodies are to be detected are attached to a polymer support. Plates with holes are produced. The desired protein (antigen) is applied to the bottom of each well, it is attached, and then serum is layered there. If there are antibodies in the serum, they adhere to this protein. It turns out three layers - antigen, antibodies of serum, which is examined and the third layer - a reagent with which antibodies are detected. This method is very sensitive. If there are antibodies in the serum, they will be detected without fail! The fact that the vaccine manufacturers stated that this method does not detect antibodies to the S-protein, but another is needed, quite clearly indicates that such antibodies simply do not exist.

- Did the vaccine developers publish data from the first and second stages of the study?

- The first stage checks the vaccine for safety. The second stage tests the vaccine for antibodies. If there are no antibodies to the S-protein, then there should be no neutralizing antibodies. The developers reported that vaccinated people have neutralizing antibodies, albeit in a low concentration. This statement seems controversial: without antibodies to the S-protein, there can be no antibodies that neutralize the coronavirus.

- Who sounded the alarm?

“Community activists tested the antibodies and showed them to be absent by enzyme immunoassay. These people are not specialists. They were selected at random for vaccination. Not receiving a positive antibody test result, they doubted the effectiveness of the vaccine. The sera were collected and given to the well-known Novosibirsk virologist, Professor A.A. Chepurnov in encrypted form for testing for neutralizing antibodies. He examined 30 sera sent by the activists and sent them the results. The activists deciphered the obtained data and received the following: neutralizing antibodies were detected in 11 sera. It turned out that five of them were obtained from people vaccinated with the Sputnik vaccine, five from people who had had a coronavirus infection. One serum from a person vaccinated with EpiVacCorona and infected with coronavirus after vaccination. Antibodies were not detected in the remaining 19 sera. All of them were taken from people vaccinated with EpiVacCorona. Some of them may have received a placebo.

The community of activists turned to the Ministry of Health with a request to organize a check and were refused, arguing that the vaccine was registered, therefore, it was good.

- That is, the EpiVacCorona vaccine does not work at all?

- Since these data are unofficial, it is impossible to officially declare that there are really no neutralizing antibodies. Therefore, a very simple measure is proposed: activists can again compile a collection of sera and send it in encrypted form to "Vector", let them conduct this research there. This will be an absolutely objective way of checking.

- And, nevertheless, people who have decided to be vaccinated are offered to be vaccinated with EpiVac ...

- Despite the fact that the third phase of trials has not been completed, and the effectiveness of the vaccine raises reasonable doubts, the drug entered civilian circulation. Millions of people will be vaccinated with it. In my opinion, this is an unjustified decision: people who want to be vaccinated with this vaccine will get sick and die just like the unvaccinated. This can lead to unnecessary loss of life. I'm not even talking about the significant compromise of our biotechnology. The use of the EpiVacCorona vaccine must be stopped pending the necessary verification.

I note that the failures of specialists who have chosen one or another platform for creating a coronavirus vaccine are quite common (Merck, USA, Sanofi, France, as well as many others who have not yet announced the termination of unsuccessful developments).

Read more about the problem with the EpiVacCorona vaccine in the article " Let's Hit EpiVacCorona on the Virus: Activists Ask to Check the Vector Vaccine".