Chumakov Research Institute Director Aidar Ishmukhametov: CoviVac's main task is to influence the immune system as gently as possible
Photo: Chumakov Research Institute
CoviVac is the third Covid-19 vaccine to be developed in Russia and the first inactivated one. Aidar Ishmukhametov, the director of the Chumakov Research Institute that developed the vaccine, spoke in an interview with Interfax about when Phase 3 of clinical trials will begin, the degree of protection that the vaccine provides, how often antibody response should be measured, and who is advised to have CoviVac administered in three-stages.
Question: Is it already known what level of protection, what level of antibodies the CoviVac vaccine provides? How long does it last and ensure protection?
Answer: The level of protection of any vaccine is not constant. The level of antibodies of those vaccinated and who have recovered from the illness increases over several weeks. It reaches a certain level and then it begins to fall. Usually, this cycle takes about from six to eight months, but some individual nuances are possible as to when the antibody titers fall below the protection threshold. Moreover, vaccination is intended to protect you from contracting the disease in standard everyday conditions, but if for some reason you get a big dose of virus, for example if you have close and lengthy contact with the spreader, the vaccine will ensure that the disease is mild.
Currently, we are seeing volunteers who took part in Phase 1 and 2 of the clinical trials and who were vaccinated last October or November keep their protective antibody titers. The level of antibody response depends not only on the individual traits of your immune system, age, coexisting illnesses and medicines taken but also on your lifestyle. Our vaccine is based on the inactivated poliomyelitis vaccine technology which is used for children from three months old. Its main task is to do no harm and influence your immune system as gently as possible. We continue monitoring how the vaccine works in line with generally recognized global standards in order to eventually include data on the period of vaccine efficacy in the medication guide. At the same time, one should keep in mind that the [effect of the] medication may last even longer in some cases.
Q.: Should the level of antibodies be measured after vaccination, and how often should this be done?
A.: How recently have you measured the level of antibodies to tetanus, poliomyelitis, or measles? And do you know what proteins of these viruses are antibodies measured? I think that the answer will be no to both questions. Moreover, in other countries there is no such culture of measuring the antibody level outside of clinical trials, and if you want to have a look at your antibodies on your own, you will have to prove the need for doing so to your physician. Earlier people used to boast about their cars, but now they boast about their antibody level.
It is also important to mention that over 150 test systems for measuring the level of antibodies have now been registered in Russia. These test systems differ in a number of ways – sensitivity, specificity, quantitative assessment option, and the antigens they are based on. Often the results obtained through various test systems cannot be compared. For example, test systems that measure antibodies to the N-protein of the virus are suitable for those who have recovered, but not for people who were administered a vaccine whose antigen is the S-protein. Only a specialist can interpret the result in a qualified way. Therefore, let's learn finally to trust scientific data and stop this unhealthy widespread craze and antibody competition. Firstly, the protective immunity is not just antibodies and not any antibody. Secondly, let's leave professional questions to professionals.
Q.: What systems will be used to measure the level of antibodies after the administration of the CoviVac vaccine? Are these systems that are already known or will the institute develop its own, as the Novosibirsk-based Vector did?
A.: Of course, it is possible to try measuring the level of antibodies after the administration of CoviVac with tests for those who have recovered. But all of them will have restrictions as to the sensitivity and specificity, which I have already spoken about. As for the professional monitoring of the results of administering our vaccine – let me stress once again not for domestic use – we are indeed working together with several producers of test systems. We hope that in the framework of Phase 3 of the clinical trials, which is scheduled to begin in June, we will be able to pick up the most accurate and objective method of assessing the level of protection of the organism in general rather than just the level of any antibodies.
Q.: Is it necessary to measure the level of antibodies after the recovery and how often should this be done?
A.: Actually, I've already answered this question. It's not necessary. We would certainly recommend getting vaccinated six to eight months after having the coronavirus infection.
Q.: Is there any data regarding the level of antibodies at which the CoviVac revaccination is necessary? Could other vaccines be used for revaccination or is only CoviVac suitable for revaccination?
A.: Our vaccine is universal. It can be used as a booster after the administration of other vaccines if your job involves constant contact with a large number of people. As a booster after illness, especially if you have chronic illnesses, and actually as a primary vaccine to protect against illness. We are skeptical about the possibility of making a decision on revaccination using any vaccine based on assessing the level of antibodies. The thing is that it is possible to assess the level of neutralizing antibodies, which are the antibodies that protect people from infection, only in an experiment with the use of native, or natural, infection virus. Such studies are made at specialized establishments that are licensed to work with such pathogens and take up quite a lot of time and effort.
I believe that in the medium term, mass vaccination will be carried out in line with epidemiological cycles for this virus rather than in line with the level of antibodies. The main thing is to interrupt the spread of coronavirus, to minimize the possible growth in the number of those infected and have fallen ill thanks to swift and mass vaccination. By vaccinating, you protect not only yourself but also you relatives, friends, and the colleagues you communicate with. And scientists will tackle individual cases. If these phenomena are significant and affect certain risk groups, they will undoubtedly find their place in recommendations for use.
Q.: Does the level of antibodies depend on the age of those vaccinated and who have recovered? Who has the higher level – younger or older people?
A.: As I said earlier, immune response is a very individual thing. Naturally, young healthy people without bad habits develop antibodies faster and more actively than older people. Coexisting illnesses and the therapy you are taking influence the development of antibodies. I think that there will be rather a lot of scientific publications to this end.
Q.: Is it necessary to vaccinate children or do they have enough antibodies to protect them from the virus?
A.: We plan to expand the list of uses for teenagers and children. I'm afraid we won't be able to effectively counter the spread of the disease if this group of people is not protected.
Q.: Is it possible that there will be no antibodies after CoviVac vaccination, and what should be done in this case?
A.: Of course, it is possible. According to the data of Australian scientists, even 10% of those who recovered after the coronavirus infection don't develop humoral immunity. None of the existing vaccines, and not only from the coronavirus, is 100% effective. There have been about 15% of volunteers in our clinical trials who haven't developed antibodies by the 56th day after the first vaccination. However, we can see as part of their monitoring that the majority of these people didn't fall ill, and those who did fall ill either showed no symptoms or had very mild illness, without hospitalization. Regrettably, there is no one rule for all. People with high antibody titers are ill and at the same time people who were vaccinated but who showed no pronounced antibody response aren't. Systems that measure T-cell immunity and are capable of partially explaining this phenomenon aren't widely used. The longer the virus stays with us, the more questions scientists have regarding the interaction mechanism of the virus and its components with humans. Regrettably, it is now impossible to get answers to all questions immediately. Let's keep in mind that infections for which vaccines were created and which got on the vaccination schedule have been studied for decades, and less than 18 months have passed since SARS-CoV-2 emerged. That is why I urge everyone to treat with understanding the fact that many questions so far have no definite answers. The whole planet has for the first time found itself in a situation where civilization is capable of responding appropriately to a threat that has emerged compared to how such events evolved before – during plague, cholera, and Spanish flu... The search for an effective response is ongoing.
Q.: At what stage is the issue of three-stage administration of the vaccine? What does this ensure? Is the issue of holding special studies regarding the three-stage use being worked on?
A.: Yes. We initially considered several options for administering [the vaccine] and carried out preclinical trials using different intervals - 14 and 21 days, as well as three-dose vaccination. In the near future, in June, we plan to officially extend the interval between the doses to 21 days. The reason for this is not only the convenience of using the vaccine in the regions, the standardization of vaccination procedures, but also the results of preclinical trials that showed that the immune response develops more actively if the interval between administering the vaccine is extended. As part of the phase 3 clinical trials, we will single out a separate group of volunteers over 60 years of age and will analyze the need for three-dose vaccination to ensure the appropriate level of protection for people with weakened immune responses.
Q.: How likely is it that the CoviVac vaccine will be administered in three-stages and when might it be administered?
A.: The need for the three-stage vaccination scheme will be analyzed in the wake of the clinical trials. First and foremost, it may be recommended for the elderly and people with chronic illnesses. If tentative results of these clinical trials show that three-dose vaccination will be effective for the elderly, this recommendation will be included in guidelines for the vaccine's use around September.