A long conversation about vaccines

Such different antibodies

Natalia Leskova, "Scientific Russia"

Do I need vaccination against COVID-19? Which vaccine should I prefer? What is the difference between the antibodies that are produced as a result of the disease and those that should appear after vaccination? Will they protect you for a long time and will they protect you? This is our conversation with Pyotr Mikhailovich Chumakov, Chief Researcher at the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, corresponding member of the Russian Academy of Sciences.

– Pyotr Mikhailovich, three vaccines against a new coronavirus infection have already been registered in our country today. Which one should I choose? 

– Indeed, we have now formally registered three vaccines. Although Sputnik V, of course, is significantly ahead. Firstly, because it was the first registered vaccine, and, in addition, the development of Sputnik is the long-term work of the team that creates such vector vaccines based on adenovirus. The choice to put it on as the first choice vaccine is quite understandable. It could have been created in the most emergency mode, which turned out to be the case.

With regard to the other two vaccines, the following can be said. EpiVacCorona is a development of Novosibirsk Vector, a peptide vaccine. This is a new type of vaccine, and the experience of their use is still very small. Their effectiveness is little known. I would say that this project is experimental. The biggest expectation was that it should not give big side effects. Therefore, if it proves effective, it will be the vaccine of choice for weakened elderly patients. But now I can't say anything about this vaccine, because there is no data on its effectiveness. I just want to say that publicly available tests for antibodies, for S-protein after vaccination in the experimental group show the absence of antibodies. At the same time, Vector has its own test system that allows you to watch the formation of antibodies against these peptides, and this system shows that antibodies appear. It is unclear to me how this can be, and this issue needs clarification. Therefore, I think that this vaccine is not yet ready for mass use, and it should not be counted on as a life-saving vaccine that can protect against the disease.

– And what can you say about the vaccine, recently registered, which was manufactured at the scientific center of immunobiological preparations, bearing the name of your father?

– This is a vaccine of the traditional plan, which includes the production of a large amount of a pathogenic virus, which then inactivates in a certain way. This is the so-called "killed" vaccine.

Such vaccines are most often used, so there are a lot of hopes for this particular one, Because unlike Sputnik V, which causes the formation of antibodies to only one S-protein, although the most important, but, nevertheless, only one, Such "killed" vaccines produce antibodies to all proteins the virus. And therefore it is possible that immunity after vaccination with KOVIVAK will be more stable and versatile. Although, again, there is currently no available data about this vaccine. Therefore, for now I would recommend it only as a second-choice vaccine. I would wait for mass application until we get acquainted with its parameters.

– Many people think that imported vaccines are a priori better than domestic ones.  Is this really the case, or are our vaccines not inferior in any way?

– In this case, this cliche is completely unqualified. I must say that vaccinology and virology in our country have always been on top. The first virus was discovered in Russia by D.I. Ivanovsky. We were ahead of many countries. Of course, the amount of money invested in our science cannot be compared with what has been happening and is happening, for example, in America and Europe. Nevertheless, our scientists are highly motivated and well prepared. And we know how to win. The same vaccine "Sputnik", developed at the N.F. Gamalei Research and Development Center, is the fruit of many decades of efforts. Such work began in the USSR back in the early 70s, when adenoviruses were studied, then they began to make various kinds of vectors from them. An Ebola vaccine has been developed on this platform. Therefore, I believe that there is no doubt, everything here is done qualitatively. The results published in two articles of the Lancet suggest that the vaccine has turned out.

As for foreign analogues. Indeed, we often treat with reverence everything that comes out of the West. But there are also a lot of problems there, both organizational and medical.

For example, the AstraZeneca vaccine is also vector-based, made on the basis of monkey adenovirus. This is good, because a person does not encounter a monkey virus. But, nevertheless, now it turns out that the AstraZeneca vaccine does not react well and does not protect well against the South African version of the coronavirus, while Sputnik protects well. And this is one of the arguments why AstraZeneca, together with the N.F. Gamalei Institute, is now making a hybrid vaccine that will be used in some countries.

As for vaccines on the mRNA platform, which have high hopes – this is also a new class of vaccines. At first, I was very skeptical about this choice for developing a vaccine that should stop the pandemic as soon as possible. The RNA that is part of this vaccine is very easily degraded by various factors, and it is very difficult to foresee everything here. For example, if the temperature regime is not very well maintained, it is unclear whether it will be effective in "field" conditions? It's one thing when this test and all its participants are in awe of following the protocol. And what will happen when mass vaccination begins? There should be very powerful logistics, and refrigerators that will provide a very low temperature.

As for the vaccine itself, in principle, it showed a good result during testing. But now there are very contradictory reviews about this vaccine regarding possible side effects. There are reports of cases of severe side effects and even deaths. It is worth investigating whether these cases are really related to the use of the vaccine. This issue, of course, should be carefully studied.

Another doubt is expressed: as a carrier, a stabilizing agent in this vaccine, a formula based on polyethylene glycol is used. There have been reports that this formulation alone may cause the formation of antibodies that will prevent the use of vaccines on the same platform against other diseases in the future. There are also concerns that polyethylene glycol may cause additional undesirable reactions in some people.

– Pyotr Mikhailovich, mass vaccination with Sputnik is currently taking place in Moscow in shopping malls and other crowded places. Of course, we are not talking about testing for IgM and IgG antibodies there. People just come from the street and get vaccinated without checking. Although we know that someone could have been ill asymptomatically, and they may have high antibody titers. Do you think it's dangerous to get vaccinated without such testing?

– In principle, there is nothing terrible in this. If we take into account the economic aspect, we must understand that these tests are quite expensive. If they are carried out by everyone, the procedure will become much more expensive. Does this make sense from a medical point of view? There is no definite answer here either. Firstly, any test gives errors. Maybe the person did not get over it, but he showed a false positive result, or, conversely, he got over the person, but the test does not show anything. Therefore, I think that in any case, you should be vaccinated, even if a person has been ill, especially in a mild form.

– And if it's heavy?

– If he has been ill in a severe form, perhaps we should wait. Now there is no reliable data yet that it is possible to get seriously ill again after suffering from the disease. I think that those who have really been ill should not be vaccinated now. Everyone else who doubts, even if they have not been tested, should be vaccinated.

– But after all, vaccination may be useless if a person, for example, has high class G immunoglobulins. Why expose your body to an extra load? After all, vaccination is not a vitamin drink.

– If you had some level of antibodies, and you get vaccinated, this is called a boost in immunology - a powerful addition of an antigen already against the background of the fact that there was a primary response. At the same time, the level of antibodies will rise very much. There's nothing wrong with that. It does not pose any danger, but perhaps the protection will be longer.

– Many people are afraid of such a serious complication of vaccination as antibody-dependent increased infection (ADE). What is this condition and how to insure yourself against it?

– Indeed, at first, the possibility of the manifestation of ADE in coronavirus infection caused concern. The nature of this phenomenon lies in the negative effect of antibodies that are produced against viral components, but bind to the virus without causing its inactivation. Such a complex of virus and antibodies is absorbed by cells, for example macrophages, which normally remove foreign products from the body, but in this case they lead to the spread of the virus through the body, cause an increase in infection. Such a scenario is also possible if the quality of the viral antigen in the vaccine is poor, when antibodies are formed that do not bind strongly enough to the virus. Fortunately, so far we have not seen confirmed cases of this kind. But, although this issue is not completely closed, this should not be a strong argument against vaccination, especially against vaccination with a "Satellite" that causes antibodies in response to an intact S-protein produced by the viral vector. 

– The next important question for many. People sign up for antibody testing in a regular district polyclinic and see the following information: you can check in this way whether you have been ill, including asymptomatically, or are ill now. But you cannot find out the level of antibodies as a result of vaccination. The question arises: why? Are these some kind of different antibodies?

– Of course, these are different antibodies. The fact is that the test for the transferred disease is a test for the N–protein, which is located inside the virus, not on its surface, and antibodies arise to it when a person is confronted with this virus and has been ill. But if you use such a test to check the formation of antibodies after vaccination with Sputnik V, then it will not show you anything.

– That is, this class of antibodies is not produced as a result of vaccination?

– Yes, it is not being developed. As a result of vaccination, antibodies are produced only for the S-protein, the surface spike, which, in fact, ensures the neutralization of the virus and the binding of these antibodies to the spike. In order to check how you have developed antibodies specifically for vaccination, you need to go to companies that do such a test. There are such companies. For example, Helix, which offers a quantitative test with which you can determine the number of antibodies, that is, to see how successful the reaction to vaccination was.

– We know that antibodies are not always produced and not in everyone, both as a result of the disease and as a result of vaccination. There are people who are immune both to vaccination and to certain viruses in general. And so, let's say a person has been vaccinated, he has not developed antibodies. What should he conclude from this – that he is still not protected from the disease and he needs to take some measures, or, conversely, he is protected and this virus does not threaten him?

– In most cases, it all depends on how much time has passed after vaccination. If, for example, a month and a half has passed after vaccination, then probably almost everyone will have a sufficient level of antibodies. Although the publication in the Lancet, which was released by the authors of Sputnik, shows that after the second vaccination there are people who have a less pronounced increase in the level of antibodies, nevertheless, the production of antibodies is observed. I agree with the authors that this level is enough so that a person does not get seriously ill. If the level of antibodies still remains low, I think it is worth considering the possibility of re-inoculation with another vaccine.

"The other one?"

– The same vaccine should not be vaccinated, because there are already antibodies to the adenovirus, and perhaps this vaccination will not be effective. After all, the titer of antibodies to the adenovirus vector will be very large shortly after vaccination, and this may interfere with vaccination. But all people are different, and the immune system reacts to everything differently. Some of them may have had concomitant diseases during vaccination, which were not noticed, but which prevented the formation of antibodies. Of course, this should not be forgotten. This also applies to often ill, weakened people, elderly people, whose immune system is also not up to par. Probably, in this case it makes sense to find out how well the antibodies have formed.

The second aspect is if enough time has passed after vaccination, and the antibodies have dropped and are not even detected. That doesn't mean much either. Usually after vaccination, even after the disease, the level of antibodies initially rises, but then falls, but there is no need for high levels. If there were no such decrease, we would have solid antibodies in our blood from all the collisions with antigens that we had.

Low levels of antibodies after a while do not mean that a person is not protected, because he has memory cells that store information about these antibodies. And as soon as a person encounters the virus again, they begin to multiply very quickly and produce these antibodies. The incubation period, which always happens during infection, is usually sufficient to ensure that the right amount of antibodies is accumulated during this time.

Although much is still unknown. For example, it is unclear what will happen if a person is faced with a huge dose of the virus? Will vaccination help to overcome the existing antibody barrier? Maybe not. But I think, in any case, a person will suffer from the disease in a milder form.

– In what case does a person need to make a decision that, perhaps, it is worth trying to be vaccinated with another vaccine, since the antibodies are low?

– If, 45-60 days after vaccination, the antibodies are still low or there are none, it is probably necessary to be vaccinated with another vaccine. Of those that I would recommend now, this is the vaccine of the M.P. Chumakov Center.

– And what kind of vaccine have you chosen for yourself, or are you still making do with those non-specific means of prevention that you continue to develop after your wonderful parents?

– I defended myself so much throughout the pandemic, but now I decided to get vaccinated, because I believe in Sputnik. I know the people who worked on it well. Publications on this topic are quite convincing. That's why I got vaccinated. I didn't check the level of antibodies, although, apparently, it's worth doing it. Now it has been just about three weeks after the second vaccination. I feel protected. Although this does not mean that it is necessary to rush into all serious, communicate with the sick. I have always had a certain skepticism about the mask, but, nevertheless, since there is such an order, we must follow it. I don't know whether it is effective or not, but I think it is to some extent effective, because this year, for example, there was no flu epidemic.

– Do you think there was no flu because masks were worn, and not because flu and covid are competing viruses?

– Well, what kind of competition is there! If, for example, this virus circulated widely and did not cause painful symptoms in most people, then yes, it would probably be a competition. And in this case, a person, when faced with a virus, in most cases gets sick. So I don't think it's a competition. Most likely, precautions played a decisive role here – both distance, and the absence of close contacts, and masks. All this has led to the fact that there is practically no flu this year.

Portal "Eternal youth" http://vechnayamolodost.ru