How and why vaccination against one disease can help against another

2024 Author: Malcolm Clapton | [email protected]. Last modified: 2023-12-17 03:44

If you look closely at them, it becomes clear that vaccines have long ceased to be what they seem.

The SARS ‑ CoV ‑ 2 coronavirus pandemic forced us to improve our knowledge not only about virology and epidemiology, but also about the work of the immune system. The well-established idea that immunity simply protects the body from external threats turned out to be far from always correct. Many victims of COVID-19 are not killed by the coronavirus as such - death is brought by the patient's own leukocytes, which destroy the lung tissue, shooting off infected cells, and breed such an inflammatory panic (the so-called "cytokine storm Cytokine release syndrome -" Wikipedia "), with which the body unable to cope.

Now we have to question another thesis from the school textbook: the vaccine protects against the pathogen from which it is made.

Vaccines seem to have many side effects - both positive and unwanted - and we can turn some of them to our advantage in the fight against coronavirus.

Kill another

When a stranger enters the body, the immune system needs time to detect it, report it to higher authorities (lymph nodes, bone marrow and spleen) and drive the troops. It would be much more convenient if the army was already on alert. That's what a vaccine is for.

Vaccination is a miniature disease. We infect our body with a pathogen, but it is so weak or passive that the war of immunity with it ends in victory in the very first battle, the winners do not suffer losses and then switch to patrolling the territory.

But what happens if there are not one, but two opponents - that is, if soon after the introduction of the vaccine, another pathogen enters the body?

The fact is that at the very beginning of hostilities, soldiers of innate immunity go on the offensive, who are not distinguished by great imagination. The tactics of their battle does not depend on who they got as opponents. For example, the antiviral response begins with type 1 interferons, which are proteins that trigger an “emergency” regime in cells. In this mode, the cell slows down the synthesis of its DNA, RNA and proteins, so that if it is captured, the virus cannot multiply. And if so, then it does not matter at all CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses, who exactly attacks the body and how many of them - an emergency stifles any enterprise.

Therefore, we can assume that if a coronavirus has entered your body, and at the same time you have just declared a state of emergency on the occasion of the war with the vaccine, it will, if not stop, then at least slow down the invasion of the new invader. Based on this, the American virologist Konstantin Chumakov, who evaluates the effectiveness and safety of vaccines at the FDA (American Ministry of Health), suggested Could an old vaccine be a godsend for new coronavirus? fight the coronavirus with a long-studied, attenuated polio vaccine. In this he inherits his parents - Russian virologists Marina Voroshilova and Mikhail Chumakov - who were involved in the introduction of a live polio vaccine in the USSR in the 1950s.

Mass vaccination not only allowed Two out of three wild poliovirus strains eradicated to get rid of two out of three types of poliovirus in half a century, but also led to unexpected consequences that were not directly related to polio. For example, in the 2000s, in African Guinea-Bissau, vaccinations reduced the National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause Mortality: A Natural Experiment within Seven Randomized Trials, child mortality by 19 percent - and this was during the years when polio in the country nobody was sick. Chinese scientists noted that children vaccinated against polio, less often Pre-existing heterologous immunity to poliovirus vaccination may mitigate severity of hand, food and mouth disease caused by EV71, develop infectious inflammations in the mouth and extremities. And in Russia, according to Could ‘Innate Immunology’ Save Us From the Coronavirus? Chumakov Jr. And since the vaccine has proven to be of great help in the fight against other viruses, why not use this weapon again?

The polio vaccine has undeniable advantages: it has been known for a long time, is well studied and is inexpensive. However, there are some subtleties here.

The fact is that there are two vaccines against polio. The first is the aforementioned live weakened - her children are dripped into the mouth or fed on a lump of sugar. And the second is inactivated, it is injected into the muscle by injection.

The inactivated one appeared earlier: it is safer, but also less effective. The parents of Konstantin Chumakov fought for the introduction of a live vaccine, which gives a stronger immune response, and since then it has been used all over the world. But gradually, as the poliovirus was eradicated, countries began switching back to inactivated vaccine so as not to put immunocompromised people at risk.

If the live vaccine is started again massively now, there is a chance that people at risk could get hurt. Therefore, even for a long-known vaccine, thorough tests are needed (they are going to be carried out, for example, in Russia, in Kirov, 1,500 studies of a polio vaccine for the prevention of coronavirus will be conducted). And if such a method of shaking up the immune system will become a salvation for someone, then only for those who are not yet sick, and those who need emergency protection - first of all, doctors.

Immunity beguiled

But while the idea of a polio vaccine still looks intuitive - after all, a cure for one virus can be useful for others - then some others seem much weirder.

For example, many were encouraged when New York scientists calculated that in countries with mass vaccination against tuberculosis, mortality from coronavirus is lower Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study than in those where the program vaccinations were curtailed. If these results were confirmed, this would mean that some countries where tuberculosis has not been defeated and vaccination against it is compulsory (for example, Russia) could breathe out with relief: if not tuberculosis, then at least the coronavirus will pass tangentially.

But TB is caused by bacteria - and COVID-19 is caused by viruses.

The article was quickly criticized by BCG Against Coronavirus: Less Hype And More Evidence, Please: the correlation was called insignificant, and the methodology questionable (among other things, the authors compared countries depending on the average income of the population, which does not always correspond to the quality of medicine). And after Tel Aviv doctors compared mortality from coronavirus among unvaccinated Israelis and vaccinated migrants and put SARS ‑ CoV ‑ 2 Rates in BCG ‑ Vaccinated and Unvaccinated Young Adults on a point in this story - mortality did not differ between these groups. You can't breathe out.

Nevertheless, the idea of comparing mortality depending on the history of vaccinations was not born out of the blue. Like the polio vaccine, which is credited with preventing other viral infections, the tuberculosis vaccine also has surprising properties every now and then.

The TB vaccine is an attenuated strain of the bovine tubercle bacillus, Mycobacterium bovis (also called the bacillus Calmette-Guerin, after its inventors, hence the acronym BCG, Bacille Calmette-Guerin). It is related to the human tubercle bacillus - M. tuberculosis.

The first surprising property of BCG is that it does not protect Tuberculosis so well against tuberculosis itself: in some populations, its effectiveness tends to zero at all.

But BCG successfully prevents leprosy caused by other members of the mycobacterium genus. There is an explanation for this effect: related bacteria have similar proteins on the cell surface. And if the body produces antibodies that sit well on one mycobacterium, then with some degree of probability they will adhere to the surface of its relative, triggering an immune response.

This phenomenon is called cross-reactivity. And it works not only for antibodies, but also for T-lymphocytes, which suddenly recognize the enemy in cells with unusual molecules and kill them - although the mechanism of their work looks the other way around, remembering a specific enemy in order to attack him at the first meeting.

Immunity can thus "confuse" not only related bacteria, but also different CD4 viruses T ‑ Cell ‑ Mediated Heterologous Immunity between Mycobacteria and Poxviruses: HIV and hepatitis, influenza and Epstein-Barr virus, bacteria and unicellular eukaryotes Harnessing the beneficial heterologous effects of vaccination (tetanus and toxoplasma) and even bacteria and viruses: cytomegalovirus and the plague bacillus, HIV and M. tuberculosis.

This leads to the fact that adults sometimes have Harnessing the beneficial heterologous effects of vaccination immunological memory cells that are specific to pathogens that their hosts have never been sick with: including HIV, herpes virus and, as it recently turned out, Targets of T Cell Responses to SARS ‑ CoV ‑ 2 Coronavirus in Humans with COVID ‑ 19 Disease and Unexposed Individuals, even SARS ‑ CoV ‑ 2 coronavirus.

One way or another, many researchers have found that the BCG vaccine has the ability to protect not only against mycobacterial infections. For example, in several populations it reduced A small jab - a big effect: nonspecific immunomodulation by vaccines by two to three times, all-cause infant mortality. And this can hardly be attributed to anti-tuberculosis protection: newborns practically do not get sick with it, which means that the vaccine can act in some roundabout way. Gradually, scientists began to suspect that this was not a matter of cross-reactivity - in some cases, the "déjà vu" effect, which allows you to cope with a never-seen pathogen, worked independently of the T and B cells with their antibodies. This means that immunological memory has other, previously unknown mechanisms.

Tricks with memory

The classic image of the human immune system is a tree with two branches: innate and acquired (adaptive) immunity. And if each person has his own second and the strength of his response depends on the memory of previous infections, then the first should be the same for all healthy people.

However, there is growing evidence that this is not the case.

Even in plants and invertebrates, which lack the system of adaptive immunity, from time to time they find signs of immunological memory: mosquitoes each time more and more actively try to kill the malaria plasmodium in themselves, and the immunity of crustaceans "remembers" their parasitic worms. There are known examples of Harnessing the beneficial heterologous effects of vaccination and of what traces the invasion of an irritant leaves in the cells of innate immunity: macrophages (eaters of bacteria and cell debris) and neutrophils (the main fighters against bacteria).

These effects are called the memory of innate immunity or manifestations of "trained immunity" Trained immunity: A program of innate immune memory in health and disease - in the case of BCG, the vaccine acts as a trainer, respectively. In memory of the trial battle with tuberculosis, the body retains not only T- and B-lymphocytes ready to fight the tuberculosis bacillus, but also cells of innate immunity with altered metabolism. For example, some of them begin to release more signaling molecules. Epigenetic shifts are outlined in them: some genes "close" from reading, others, on the contrary, unwind, as a result, the set of secreted substances also changes.

Judging by the fact that some manifestations of immunological memory persist Trained immunity: A program of innate immune memory in health and disease for months or even years after the first "training", changes affect not only adult cells, but also stem cells that continue to produce activated predecessors. Even "civilians" are trained: the inhabitants of the bone marrow and epithelial tissues, after infection or vaccination, continue to produce more molecules that direct the movement of immune soldiers throughout the body - and this determines, for example, how many of them will come running into the lungs to fight the coronavirus.

We can not always fully predict whether these changes will occur in the case of each specific vaccine, and if they do, then in which direction they will be directed.

Some antigens-irritants cause immunity tolerance, that is, suppress its work. Others, on the other hand, keep the immune system on track and allow it to react more aggressively to other enemies. In some cases, these actions can be combined: the trained immunity will react more strongly to some stimuli, and weaker to others.

In each case, it is necessary to carefully check what kind of memory the antigen leaves behind. Sometimes these effects can be disadvantageous to us - for example, one of the influenza vaccines was associated with Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2 with autoimmune narcolepsy. And sometimes "vaccine training" can be used to benefit people. For example, BCG are considering using Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS for multiple sclerosis and are already experiencing Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations as a cure for diabetes: Vaccination in infancy is not beneficial here, but the emergency administration of the vaccine helps to muffle the body's autoimmune attack on the pancreas. The same vaccine is beneficial in other cases. Trained immunity: A program of innate immune memory in health and disease to enhance the immune response in bladder cancer, leukemia, lymphoma and melanoma.

Now we have the opportunity to BCG-induced trained immunity: can it offer protection against COVID-19? take advantage of the newly discovered property of innate immunity and turn its "memory" against the SARS ‑ CoV ‑ 2 virus. It hardly makes sense to count on the residues from childhood vaccinations - the data on how long the effect of training after BCG persists in the body varies greatly - from several months to decades (although there is even work in which it was possible to trace Maternal Priming: Bacillus Calmette- Guérin (BCG) Vaccine Scarring in Mothers Enhances the Survival of Their Child With a BCG Vaccine Scar (intergenerational effect: children died less often and responded better to the vaccine if they were born to a vaccinated mother). But you can re-vaccinate adults and hope for quick protection (but possibly short-term).

In this case, as in the story of the polio vaccine, there are risks. If the immune system responds too aggressively to the vaccine, a cytokine storm can occur, which the body is not always able to cope with. However, in a similar study, BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity, when BCG was used against the yellow fever virus - Wikipedia, this did not happen, and the vaccine worked successfully. But in an epidemic, one cannot be sure that people with weak immunity and the elderly will adequately respond to vaccination. Therefore, while clinical trials of BCG as a prevention of COVID-19 are already beginning around the world, from Denmark to Australia and Uganda, they will be targeted primarily at medical professionals.

Thus, the new coronavirus can act here as an engine of immunological progress. With other drugs to be found for diabetes or cancer, preventive vaccination trials are unlikely to reach such proportions. Now we have a chance to collect a large amount of data on how the vaccines we are used to work in a roundabout way, and to check whether our innate immunological memory is so strong.