New strains will replace SARS-CoV-2 undoubtedly. And we didn’t even have time to protect ourselves from the old ones.
We spend our whole lives getting vaccinated against certain diseases. And only when there is an outbreak of measles, we are told: “If you do not know whether you are vaccinated or not, take an antibody test or get vaccinated, the vaccination is well studied: it will not harm, even if you once did it.” Even doctors themselves regularly check the level of antibodies to hepatitis B-when they decrease, they are revaccinated. For other infections, no one recommends checking them: it is known about long-existing vaccines, who produce antibodies for them, who does not, who will have more of them, who will have less, it is known how their formation depends on gender and age.
In the coronavirus pandemic, these very antibodies became a popular topic. At the same time, some say that it is necessary to check them, while others do not necessarily. And still, others are trying to figure out which ones are better — post-vaccination or those that were formed after the disease.
Approximately the same people relate to vaccination: some are not in a hurry to get vaccinated-they are waiting for the perfect vaccine. Others are vaccinated with everything they have; they want to get high antibody titers to protect themselves by 150 %. Do a double vaccination, see that there are few antibodies, and “catch up” with the third dose, that is, the first in the vaccination scheme. After that, they find homegrown ways to strengthen the immune response on the Internet — with the help of “immunostimulants,” “to increase the production of antibodies.” And someone hopes for cellular immunity.
“I have a strong cellular immunity”
… It is often said by those who have not yet fallen ill and have not been vaccinated. The formation of cellular immunity is also reported by vaccine manufacturers. Although none of them did any research on it.
Reference. The cellular immune response consists in the fact that the T-cells of the immune system recognize and remember the pathogenic organism – the antigen, transmit information about it to other parts of the immune system, which destroy it without the participation of antibodies. In the humoral response, the B cells of the immune system, in response to the penetration of the antigen, form antibodies that fight it.
“In an attempt to explain why there are people who are not susceptible to infection, they talk about cellular immunity, saying that it “at the entrance” fights the virus. We don’t really know that. In theory, the T-cell should identify the virus-infected cell and give the signal for apoptosis – its destruction. But it can fight one infection like this and do nothing against another. It is impossible to examine every T cell to see if it can fight the coronavirus or not. These are long-term and very voluminous studies and the results of their conduct on animals cannot be extrapolated to humans. I am afraid that the statements about the formation of cellular immunity after the disease and after vaccination are a pseudoscientific approach,” the doctor explains. “Immunology is a mysterious science. We do not always know how the immune system works in a particular situation in a particular person, what is good for him and what is bad. We don’t even know why a person produces a lot of antibodies — because they have a lot of B cells responsible for their production, or one B cell can produce a lot of antibodies? One thing is known: the more of them, the better the body is protected. And today, this is the only way to assess the level of protection against the virus.”
“Quickly, quickly get vaccinated. Otherwise, the mutants will come”
When a person has a choice, doubts begin: “I will not be vaccinated with this vaccine, I will wait for another one.” The ideal vaccine seems to be absolutely safe, effective — with a full-fledged immune response (both cellular and humoral), disposable, and better in the form of a pill, not an injection. It would also be good if it was easy to store and transport. None of them is perfect, there is no such thing today and in the whole world. And doctors, who six months ago themselves doubted the need to be vaccinated, are now sure that it should be done as quickly as possible.
Specialists, who worked for a total of six months in the red zone, say: “We can’t wait for the perfect super vaccine to appear — we may not live to see it. We now need to vaccinate as many people as possible to stop the spread and mutation of the virus. Because the longer it circulates and stays in the human body, the better it feels. The case of a patient with an oncohematological disease, in which the virus was isolated for up to 184 days, is described. And when they analyzed what it was like at the beginning and the end, it turned out that in six months it mutated more than 20 times. How many people received different viruses from it, how and at what stage, is unknown. You can save your life, the lives of your loved ones and create a collective immunity only when everyone gets vaccinated. By stopping the transmission of the virus, we will also stop its ability to change.”
To properly orient their patients, doctors study everything that becomes known about vaccination at home and abroad. And the information about it is expanding every month. As well as information about the mutation of the virus, which makes it more dangerous. Therefore, we are ready to push ourselves: quickly, get vaccinated, otherwise, mutants will come.
What vaccines are used to vaccinate the world
Each country has approached the creation of a vaccine in its own way, based on an understanding of the nature of the new coronavirus. We know that it penetrates the cell and uses its resources for self-replication. When compared with other dangerous respiratory viruses (H1N1 influenza, SARS-CoV-1, MERS), it has the longest incubation period: 4-17, and on average 5-6 days. At the same time, each person infected with SARS-CoV-2 transmits the infection to a large number of people, because two days before the onset of clinical symptoms, he already becomes a distributor of the virus: at this time, he feels healthy and does not assume that he can be contagious.
This virus has a very complex structure: the nucleus, whose DNA and RNA allow it to reproduce, spikes – they contain three types of protein (S, M, and E), the most important — S-protein, with which the virus attaches to the ACE-2 receptors on the membrane of the host cells. In most vaccines under development, the S-protein is used as an antigen to which an immune response should be formed. And they create them based on different platforms – so far only those that already existed at the time of the appearance of SARS-CoV-2. But scientists are also working on vaccines of the future: the first ones are based on artificial antigen-presenting cells that are introduced into the body and, as it were, tell it: “We are coronavirus antigens, make antibodies to us.” They themselves do not carry any viral load. The second – based on virus – like particles to different variants of the coronavirus. We don’t know what other platforms may appear. But their creation will take years. The proposals made today are based on what is available and have already been tested. That’s why they were able to appear so soon. Each platform, and therefore the vaccine created on it, has its pros and cons.
1. Vaccines based on the killed virus. The old method is almost 100 years old, the most striking example — vaccines against polio, hepatitis A, influenza. In their image and likeness, the KoviVak vaccine and the Chinese CoronaVac (Sinovac) are made. It is known that since it is made from a whole virus, it means that the immune response will be to the very core of the virus. Namely, it changes in the process of mutations.
The advantages of this vaccine are that it is easy to store and transport, it is quickly produced on a well-studied platform.
Cons: there is a risk of a more serious course of the disease, difficulties for people working in production, where a live virus is used in large volumes, the result of vaccination is only a humoral response (the appearance of antibodies to the virus). And the biggest disadvantage is that this vaccine is based on coronaviruses obtained from the first patients. And experts have doubts about its effectiveness against new forms. Therefore, probably, the European countries did not follow this path — only Russia and China tried.
2. Vector vaccine. Created on a platform developed for the production of an Ebola vaccine. It should trigger the production of antigens by the body’s own cells, which is what the immune system reacts to. Positive: fast and safe production. The downside is the possibility of immunity to the selected vector (in the case of Sputnik, these are adenoviruses), because of this, the immune response to the coronavirus can be reduced, and repeated administration (after a year or two) is meaningless.
Vaccines created on this platform: Sputnik V (Russia), Convidecia (China), AZD-1222 (Astra-Zeneca, UK), and AD-16 (J&J, USA). In the Russian and American vaccines, human adenovirus is used as a vector, and in the Astra-Zeneca vaccine, ape adenovirus is used.
3. Protein vaccines are produced on the same platform as diphtheria and tetanus vaccines. The technique is 100-year-old. Its advantages are the ability to quickly establish safe production; the disadvantages are low efficiency, difficulties in obtaining high-quality protein, and, in the end, that they clearly form only a humoral response. At present, we know about six developed protein vaccines (USA, China, Australia, Taiwan, France, and Russia). Today, only the Russian (EpiVacCorona) has reached the 4th stage of research, although for some reason it is called not protein, but peptide. That is, not even a whole protein was taken, but a fragment of it.
4. RNA vaccines. Created on a new platform designed for a vaccine for the treatment of lung cancer. It is still poorly understood. For production, a piece of RNA is taken, which triggers the production of antigens in the body, and the immune system reacts to them.
Positive: fast and safe production, high efficiency. Cons: the platform is not fully understood, the vaccine must be stored at a low temperature. There are four of them in the world: Moderna (USA), Pfizer/Biotech (Germany/USA), Curevac (Germany), and Gennova (USA/India).
Stopping the spread of a virus means stopping its changes
In the 2021 pandemic, the main question is: will immunity after the disease and after vaccination work against new strains? Will these same vaccines and post-vaccine antibodies protect us?
— The probability that the immunity formed to the S-protein of the spike will be effective is very high. Because the spike is unlikely to change without it, the virus will not be able to attach to a human cell. As for other vaccines, there is no answer yet, — experts say.
The real clinical practice of an entire country – Israel – has shown that it is possible to stop the spread of coronavirus and prevent the death of people through vaccination. The reports honestly say, yes, vaccination does not protect all vaccinated people. 8 % fell ill, but only a few of them needed hospitalization and none of the vaccinated patients died. In the country, vaccination has also protected against the mutation of the virus. However, although population immunity has been achieved there (60 % of adults are vaccinated and begin to vaccinate children – the source of the spread), the external borders remain closed. Israelis are afraid of the introduction of new strains — Brazilian, Indian, South African, they are more contagious, can avoid both natural and vaccine immunity, and affect the morbidity and mortality from COVID-19.
Vaccination should be actively carried out all over the world. But there is no doubt that the new, more contagious variants of SARS-CoV-2 will replace the previous ones everywhere. The effectiveness of some vaccines against new strains has already been compared. In Novavax and Astra Zeneca, it is reduced against the British strain by 10 %, against the South African strain – by almost 30 %. Against the South African, Astra Zeneca retains minimal protection against mild to moderate disease; Jonson&Jonson has reduced protection by 15 %, and Novavax – by almost 30 %. But they still protect those vaccinated with these drugs and those who get sick from death — the antibodies obtained as a result of vaccination against old strains of coronavirus work. The study involved 15 thousand people.
Who is better protected — ill or vaccinated?
In relation to any infection, doctors usually say that the immunity of the patient who has been ill protects against a new infection better than the immunity of the vaccinated one. And it seems that in the case of coronavirus, the situation should be the same — during the disease, the body fights the whole virus, and the vaccinated only with some part. But no. “We do not know what each person has formed antibodies to after the disease because we only determine those that we want and can detect. If found the S-protein, it is considered that they have found antibodies. And if you ask the question: is there anything else? No one knows. Adding to the uncertainty is that this virus doesn’t behave like other viruses. For example, the body in response to any infection immediately produces immunoglobulins A (at the very beginning of infection), then-M, and G-after a while. When they started using the study for immunoglobulins M and G instead of PCR-for rapid analysis, they received results that did not correlate with clinical manifestations in any way. It happened that a person in the acute phase first formed immunoglobulins G, and only then M. Or a person’s PCR is negative, and immunoglobulins M are constantly increasing for six months. Why? We will be able to get answers only after global research, stretched over time. But we know that people get infected and get sick again, so the natural immune system does not protect at least everyone. So, you need to insure yourself and get vaccinated with the available vaccine.
Waiting for the perfect one in the coming years is pointless.
— We broke our heads ourselves, thinking whether we should or should not be vaccinated. We listened to lectures, read articles in scientific journals, discussed, argued. And if six months ago many people said that it was not necessary to be vaccinated (it was not clear what and why), now they are sure that it is necessary. Yes, getting vaccinated in the midst of a pandemic is dangerous. But now, when the incidence is still far from the winter peak — it’s time, – say experts who worked in the red zone.