Russian developer of Sputnik V: we are now on the path to creating ‘canned food’ for future vaccines
Denis Logunov on how scientists are preparing to fight dangerous pathogens
Deputy Director of the National Research Center for Epidemiology and Microbiology. N.F. Gamalei of the Russian Ministry of Health Denis Logunov in an interview with TASS told how the creation of an Ebola vaccine influenced the development of a coronavirus vaccine, how scientists are preparing for the emergence of new infections, and also about the prospects for fighting HIV .
– Denis Yuryevich, tell us about the vaccines of the Center. Gamaleya against Ebola. Are they currently in use in Africa?
– In Africa, the Ebola vaccine “GamEvak-Kombi” was used in clinical trials that were conducted in Guinea in conjunction with the Military Medical Academy. CM. Kirov. There is also the FiloPan vaccine, but its development was completed in the first phase of clinical trials. This is a quadrivalent vaccine, clinical studies of which were carried out only on the territory of the Russian Federation. The contingent of subjects was limited – in my opinion, 50 people. Based on the vaccination, the immunogenicity of the vaccine preparation was determined in relation to each of the strains included there – three types of Ebola fever and Marburg fever. If there is a request for the use of this vaccine in Africa, naturally, our production facilities can be connected to address this issue.
“Some vaccines, such as influenza, need to be updated periodically for new circulating strains. Do you see the need for this modification of the Ebola vaccine?
“We don’t see it, because Ebola is not the flu or covid. Natural focal viruses do not mutate as quickly as viruses that are already stable anthroponoses (infectious diseases whose pathogens can only parasitize in the human body – TASS note).
— Did the experience of working with the Ebola vaccine help in creating the Sputnik coronavirus vaccine?
“When we worked with Ebola, we realized that an injection with one vector would not be enough to form a powerful immunity. Therefore, in the development of the vaccine, we switched to a prime-boost scheme, when two-vector immunization is provided: a vector based on the vesicular stomatitis virus and an adenovirus vector. Then we tested the same story when developing a vaccine against MERS – the Middle East respiratory syndrome, and then against SARS-CoV-2.
Without Ebola, we would not have come up with the concept of heterologous prime-boost immunization. That is, without the Ebola vaccine, we would not have come to the two-component Sputnik V.
— Is Sputnik V widely used in the world?
— Several countries have registered and used our vaccine preparations. In particular, I am aware of the application experience in Guinea. In general, 71 countries in the world have approved the use of Sputnik. The vaccine has been fairly well used and is being used. There has been debate in some countries over the use of a full two-component Sputnik V or a half Sputnik Light. There were no other critical issues regarding Sputnik.
How is the Center now? Gamalei cooperates on health issues with African countries?
“We are not currently working directly with Guinea or with any of the countries in Africa, but we understand that this continent may be a consumer of a number of vaccines against certain pathogens, in particular Lassa fever and Marburg fever. We have already implemented one government task: we have developed a panfilovirus vaccine that has passed the first phase of clinical trials against all pathogenic human filoviruses – both Marburg and Ebola virus variants. In addition, we are currently conducting the first phase of clinical trials of a vaccine against Lassa fever (GamLassaVak), which is also an endemic pathogen for Africa.
Accordingly, we have a whole pool of projects and a line of products that can potentially be used both in African countries and in the Russian Federation in case of importation of infections. In addition, we are now making a vaccine against West Nile fever, which can also be an imported infection. We always focus on the interaction and possible use of our drugs not only in Russia, but also in African countries.
— Are African countries interested in these vaccine preparations now?
– We work on the fact of the appeal. The center has a protocol for communication with foreign territories and an international department of the Russian Ministry of Health. Accordingly, if there is any need, as was the case with Ebola, we respond.
Now we are on the way to creating the so-called canned food – the basis for future vaccines. There are especially dangerous pathogens that can pose a threat both in Africa and in the Russian Federation. We must have a set of vaccine preparations, not necessarily brought to mass production, but passed the first and second phases of clinical trials, which can be quickly translated into medical practice if necessary. It seems to me that this is the right way, in which we are independent of trends and understand exactly what can be done.
— In your opinion, what diseases characteristic of the African continent now have the greatest pandemic potential?
“Probably West Nile.” She has already got to Russia, so we pay special attention to her.
In principle, there are a lot of all sorts of viruses belonging to the group of arbovirus infections (a group of infectious diseases caused by arboviruses, which are carried by arthropods – TASS note), which are very often brought to our south or already exist there. But we do not yet consider them as actual pathogens against which it is necessary to develop vaccine preparations, because we are talking about either isolated cases of the disease or a small number of cases.
“Why is it West Nile fever that worries me?”
“The main indicator for us is the presence of morbidity. If we see that the incidence is growing, there is an outbreak, then we are potentially at risk. This risk just needs to be worked out – to have the very “canned food” that, if necessary, can be used either in large quantities, or in risk groups, or for individual purposes.
West Nile virus is mainly transmitted by mosquitoes from birds, then it enters the human population. Since this infection is still unusual for Russia, but may become one, we are naturally developing a vaccine for our population. However, this infection is typical for Africa, so we can and plan to broadcast our developments to African countries.
There are several antigenic options for a future vaccine that we are now planning to test, and, accordingly, several antigenic forms. Approximately three to five designs will be created this year, and in the next three years we will reach clinical trials. If there is a positive response from the state or from foreign countries, this can be translated into practice, as in the case of Ebola.
– What do you think, what is the probability of importing Marburg fever to Russia?
— The probability of delivery, of course, is. For example, when flying. Naturally, there were imported cases of Marburg fever in the world, so there is no guarantee that we will not have this. This infection is less transmissible (contagious – approx. TASS) than influenza and covid. You just need to have a certain reserve of vaccine that will cover risk groups. It is unlikely that we will need to mass-produce a Marburg vaccine.
“Last year there was an outbreak of monkeypox on the planet. The total number of people infected in the world, according to the World Health Organization, has exceeded 86.7 thousand people. Center them. Gamalei planned to study the persistence of immunity against monkeypox in people vaccinated against smallpox?
— Yes, the results have already been published in the scientific journal Frontiers in Immunology. It was a large study conducted in collaboration with the Moscow Department of Health. It showed what we expected: everyone who was once vaccinated against smallpox, have more antibodies. That is, the older the person, the more antibodies he has. But these figures need to be looked at very carefully, because they are obvious. They cannot be broadcast in such a way that if the infection becomes stable in the human population, such numbers and antibody levels will prevent infection and, albeit small, but mortality from monkeypox.
— Another urgent problem for the whole world is HIV infection. There is still no vaccine against HIV. What is the complexity of its creation?
— There are many moments. One of them is the method of persistence (the ability of pathogenic species of microorganisms to survive for a long time in the body – TASS note). The human immunodeficiency virus becomes part of our genome – you cannot pull out a provirus from a random place (the virus genome is embedded in the DNA of the host cell – approx. TASS) and, thus, get rid of it.
Many cells become targets for HIV, but first of all, these are T-helper lymphocytes CD4 + – T-cells that regulate the work of other cells of the immune system, they are an extremely important link in immunity. What actually causes AIDS? When all CD4+ cells die, the person enters an immunosuppressive state and dies as a result.
Another important point is that HIV is highly variable. In the patient’s body there is always a depot of the virus that produces it. These virions (viral particles – approx. TASS) change as a result of the mutation process. That is, our immunity does not have time to overtake this evolution and interrupt the chain of transmission within the body. This results in a very diverse population of strains that constantly evade our antibodies and T cells. But there are also nonprogressors – people with HIV who do not show the disease for a long time. There are very few of them in the population.
– Do you think a vaccine can appear, given the variability of the virus?
“Of course, we are thinking about it. It is clear that in the last 40 years people have been struggling with the idea of creating a vaccine, but so far it has not been very successful. In principle, there is a certain phenomenology that allows you to rely on it in attempts to create new versions of vaccine preparations. Therefore, we need to continue to create vaccines. This is where an mRNA vaccine platform can help – you can immunize a patient often, a lot, and for a long time, even with weak T-cell immunogens. This is where this technology can shine.