Speculation around Ebola

Vaccine for official use
The developers do not disclose details
creation of Russian vaccines against the Ebola virusNadezhda Markina, "Newspaper.

Ru»"Newspaper.

Ru" tried to understand the situation with the creation of Russian vaccines against the Ebola virus. What kind of vaccines they are, how they were created and what effectiveness they showed in animal testing, developers and officials do not say. About the history of the work of Russian scientists with the Ebola virus "to the newspaper.Ru" said Alexander Chepurnov, former head of the laboratory of particularly dangerous infections of the Vector Research Center.

There are many vaccines – there is no effectThe world is anxiously following the onset of Ebola, from which more than 4 thousand people have already died, and looks with hope at scientists working on medicines and vaccines.

To date, several vaccines have been created and prepared for testing, and some of them are already being used. In the USA, human trials of the Canadian VSV-EBOV vaccine have begun, which has shown 100 percent protection on animals. WHO named the most promising recombinant vaccines VSV-EBOV and ChAd-EBO, developed on the basis of vesicular stomatitis and adenovirus, in which Ebola virus proteins are embedded. The American experimental vaccine TKM-Ebola is already being used for treatment with the permission of local authorities, and the creators of several more vaccines in the United States have received permits for clinical trials.

The fact that three Ebola virus vaccines (one based on an inactivated virus and two genetically engineered ones) will be presented in Russia within six months was recently announced by the Minister of Health Veronika Skvortsova. The work on the Russian vaccine against the Ebola virus is at the final stage, Russian Deputy Prime Minister Olga Golodets also said. Finally, according to Rossiyskaya Gazeta, the chairman of the State Duma Committee on Science and High-Tech Technologies, Academician of the Russian Academy of Sciences and the Russian Academy of Medical Sciences Valery Chereshnev also reported this. According to him, two institutions were engaged in the development of vaccines at once: the Virological Center of the Research Institute of Microbiology of the Ministry of Defense in Sergiev Posad (Zagorsk-6) and the State Research Center of Virology and Biotechnology "Vector" in Novosibirsk. Chereshnev clarified that the vaccines have been tested on animals.

On the eve of the Deputy Director General of Vector, Alexander Agafonov, at a press conference in Novosibirsk, said that "the scientists of the center have designed several vaccines against the Ebola virus." He added that some of them have already been tested on animals. Scientists will identify the most effective of the developed vaccines and focus on it." According to Agafonov, published on the Siberian website, one of the vaccines protects guinea pigs and monkeys from the Ebola virus, but "it is premature to say that it is effective and safe for humans."

"Newspaper.Ru" has repeatedly tried to contact vaccine developers to find out more details. Alexander Agafonov refused to give an interview by phone, referring to the ban of Rospotrebnadzor, which is the parent organization of the SSC "Vector". A request addressed to the head of the organization Anna Popova was sent to Rospotrebnadzor on September 1, but no response has yet been received. So today there is very little official information about Russian vaccines against the Ebola virus, which raises a lot of questions that have no answers.

Heroes from a closed laboratoryThe laboratory of particularly dangerous infections in Vector, which was headed by Doctor of Biological Sciences, Professor Alexander Chepurnov, was closed in 2005.

Although Russian scientists have been working with the Ebola virus since the 80s of the last century: at that time, the deadly virus was considered as a biological weapon. According to experts, Russian scientists at that time had a serious priority in these works.

Now it is puzzling who and how in such a short time brought the vaccine, and not one, but three, to readiness. And why the successes of Russian virologists are not reflected in scientific publications.

The former head of the laboratory of particularly dangerous infections of Vector, Alexander Chepurnov, who now works at the Institute of Clinical Immunology of the SB RAMS, told the newspaper.Ru" about his work with the Ebola virus and shared his thoughts on the creation of Russian vaccines.

When asked to comment on the words of the Minister of Health and the Deputy Prime Minister, and now the leadership of Vector, that three vaccines against the Ebola virus have been developed, Chepurnov replied: "I have seen the words of Alexander Agafonov about three variants of the vaccine. Unfortunately, no details. Therefore, it is very difficult to conclude whether it was really possible to assemble some kind of construction or whether the desired is given as valid. And in general, what is it: a recombinant vaccine or an inactivated one? What is the protection index for laboratory animals, primates? If it is expected to go into production in six months, then everything should be known today. After all, if they proceed to preclinical trials, the effectiveness of the drug should already be studied and these data should be published. It is clear that the lack of clear information with the well-known personnel pogrom carried out by the previous directors of Vector causes a certain distrust. It seems to me that in this situation it would be advisable for the Ministry of Health to assemble a temporary research team of the strongest virologists and molecular biologists of the country and set the task of designing an effective vaccine and immunoglobulins as soon as possible."

Chepurnov himself began working with the Ebola virus in 1988. "Already in 1996, at an international conference, we had six poster presentations, and each of them was a breakthrough direction of the international level," the scientist recalls. – The strongest work, perhaps, is that we were able to find an approach to study the genetic basis of the virulence of the Ebola virus. Usually, when infected with the virus, only humans and primates get sick. We injected the virus into guinea pigs, selected animals with some manifestation of the disease, isolated the virus from their tissue and injected the following. So we got a strain of the virus that started killing guinea pigs. If you compare its genome with the genome of a wild strain, you can find genetic virulence factors. In 2000, we were able to identify two nucleotide substitutions (mutations) that determine the virulence factor.

Another brilliant job is obtaining an immunoglobulin against the Ebola virus. Immunoglobulins are antibodies that are injected into the body to protect it from the virus after infection. We received goat immunoglobulin.

And with the vaccine, we worked like this. At that time, they tried to make a vaccine without any tricks, according to the standard method. Newborn mice are infected, they die by the 10th-11th day, their brains are taken away from them and they receive a virus-containing suspension. If you add formalin there, you will get a very dirty, but still a prototype of a vaccine with a killed virus. Then they adapted to do all this on cell culture. The cell culture is infected, then harvested, killed with formalin – the prototype of the vaccine is ready. But we need to see if it protects laboratory animals. We checked, and it turned out that it does not protect. Then I managed to get a highly purified and highly concentrated preparation of the virus, and I was sure that now I had the vaccine in my hands. But when I tested it on guinea pigs, I got only a little protection, and there was no protection at all on monkeys.

So we showed that the vaccine from the killed protein did not protect against the Ebola virus. And then I managed to show why. It turned out that in the process of inactivation, when formalin is added, denaturation of the surface protein occurs, which is responsible for the production of neutralizing antibodies. It's just that there are antibodies, but there will be no neutralizing ones if animals or humans are vaccinated with a killed virus. Although virologists from Sergiev Posad received protection on primates, they, firstly, used a huge amount of the virus, and secondly, added a very toxic adjuvant (enhancing drug) for this. It cannot be used in public. Secondly, it was found that two proteins out of seven viral proteins have the ability to block the production of interferon and interfere with the immune response. And a year ago, Alexander Bukreev showed that these proteins block the maturation of dendritic cells – one of the types of immune cells. That is, the Ebola virus has a whole set of signs that interfere with the immune response.

A working vaccine could only be made recombinant. To do this, they took a carrier in the form of another virus and put a surface protein of the Ebola virus on it by genetically engineered methods. Such a vaccine, if administered, can penetrate the cell and provoke the production of antibodies, including against surface protein.

Such vaccines were made abroad, but with the participation of our scientists, former employees of Vector. Viktor Volchkov is currently working at the University of Lyon, he provided some components to make a prototype of a vaccine based on the vesicular stomatitis virus. And Alexander Bukreev, who is now working at the National Laboratory of Galveston, USA, entirely made himself a prototype of a vaccine based on the parainfluenza virus. And the third option, adenovirus, is an American development.

By 1996, we were making the same recombinant vaccine based on smallpox vaccine, but we took the wrong protein and got a not very strong response. And we decided for ourselves that we must first deal with the pathogenesis of the virus in the body. Understand why the virus kills. So we have suspended work on the vaccine for now. I gathered everything into one article and published it to understand where to go next.

And in 2004, there was a shock when our laboratory assistant, Antonina, died after being pricked by a needle from a syringe. It's hard to say why the immunoglobulin didn't help her, but we think that's the point. For her, it was not the first, but the third incident with the Ebola virus. She received immunoglobulin, and everything ended well. But, apparently, since this is a foreign protein, horse immunoglobulin, we think that antibodies to it have accumulated in her body. And this time it didn't work."

According to Chepurnov, at the time of closing, the laboratory was on the rise: "At least we were working, and we were doing well." "When Rospotrebnazdor appeared, it was simply closed – and that's it, without explanation. A week later I received an invitation to work in the USA. I worked at the University of Michigan, and returned in 2008."

At the request of the correspondent of "Gazeta.En" to provide more information about the Russian vaccines that have appeared, the scientist gave the following advice: "Ask: what kind of vaccine, how it was made, what results it showed. And who did? Who are the heroes? These are heroes, the country should know them."

Speculation around EbolaProfessor Mikhail Shchelkanov, head of the Laboratory of Virus Ecology at the D.I. Ivanovsky Research Institute of Virology, who worked as part of the Russian Ebola control team in Guinea and, upon returning, told the Newspaper about it.

Ru", also commented on the statements of the Minister of Health Veronika Skvortsova that three Ebola vaccines have been developed in Russia, and one is from an inactivated virus, and two are genetically engineered.

"Such information is for official use," the professor replied. – Only specially authorized officials – representatives of the press services of the Ministry of Health and Rospotrebnadzor, for example, have the right to give answers to such questions. Veronika Igorevna, being not only the Minister of Health, but also a high-level expert, certainly said exactly what could and should be said. Thus, it seems to me, it is enough to quote it without comment."

When asked to clarify the statements of Deputy Prime Minister Olga Golodets, who mentioned that one of these vaccines was tested in a laboratory in Guinea, where Mikhail Shchelkanov worked, he suggested that someone misunderstood what was said.

"In the Republic of Guinea, our domestic test systems for ebolavirus Zaire are currently being verified, which, by the way, have proven themselves from the best side and meet the most demanding international standards. Field trials of the vaccine are not being conducted yet," the scientist said.

When asked whether Russia needs its own vaccine against the Ebola virus, despite the fact that its spread, even if it enters the country, according to experts, is very unlikely, Shchelkanov replied: "Russia is one of the most developed countries in the world and historically the undisputed leader in the field of virology. Realizing (including for this reason) the full extent of its responsibility to the world community, Russia cannot indifferently observe the development of the regional epidemic in West Africa. This is the first. And secondly, the vaccine, of course, will not be used en masse in the Russian Federation - there are no indications for that. However, it would be right to vaccinate specific risk groups: employees of embassies, companies with interests in West Africa, representatives of international missions. Thirdly, any epidemic outbreak should be considered as an opportunity to verify and appropriately develop the state's own biological security technologies, and here, too, Russia cannot rest on the laurels of an advanced virological power, but must act quickly, effectively, in accordance with the norms of international law."

Mikhail Shchelkanov noted that "Russia has a stock of specific antiviral antibodies and drugs based on them for passive immunization against ebolavirus Zaire," however, "information about the size of stocks and their dosage forms again belong to the category of "for official use."

"It's not like one sneezed and everyone got sick"The situation with the development of Russian vaccines "to the newspaper.

Ru" commented a scientist who wished to remain anonymous, who worked in Russia and now lives abroad.

"Developing a vaccine is a very difficult task, it's a job for an entire institute for 10-15 years," the expert believes. – Getting some kind of strain is only a small part of the work, a very large part is taken up by testing, security checks. To get a weakened strain of the virus, to test any vaccine, you need a vivarium with a very high level of biosafety. And even if you have a genetically engineered construct that has a piece of the Ebola virus inserted into it, that doesn't make it a vaccine yet. Such work could be carried out in Vector, but recently it has been ineffective and besides, everyone has fled from there, so I very much doubt that such a vaccine could be created."

At the same time, the interlocutor of the "Newspaper.Ru" stressed that if a vaccine against the Ebola virus is created, it should contain the epidemic, even without having 100% effectiveness:

"Ebola does not spread as easily as flu or measles. It's not like one sneezed in a subway car – and everyone else got sick. Infection requires physical contact with the patient or with his secretions. Therefore, if at least every second person has immunity, the epidemic will be much easier to stop. And the vaccine does not have such high efficiency requirements as the polio or measles vaccine, which should protect almost 100%. Therefore, if the vaccine protects at least by 50%, it can reduce the scale of the epidemic by four times or even more."

Portal "Eternal youth" http://vechnayamolodost.ru15.10.2014