One of the first mentions of a flu-like illness dates back to 412 BC. Hippocrates described a respiratory disease and called it the “Perinthian cough.”
Influenza epidemics claimed the lives of millions of people; for centuries, scientists could not figure out the cause and learn how to defeat this disease. It would seem that in the modern world there should be no questions left, but every year there are 3-5 million cases of severe illness and 390-650 thousand deaths! And the topic of vaccination continues to become overgrown with myths. Why doesn’t the vaccine protect 100%, why is it necessary to develop a new one every year, and why is it especially important to get vaccinated against the flu in the context of COVID-19? The answers are in our review material.
Early 20th century: Spanish flu
The most famous flu pandemic that everyone hears is the Spanish flu. It is not known for certain where the pandemic began. It is believed that China was among the first countries. A little later - America and France, and only a few months later - Spain, Italy, Switzerland and then the whole world.
The Spanish flu is a flu, its pandemic lasted two years (1918-1920), about 30% of the planet's population (about 550 million people) became infected, and up to 50-100 million people died.
A distinctive feature of the disease was the rapid development of severe pneumonia. The Spanish flu claimed the lives of the younger generation, almost without affecting people 50-60 years old. Later, medicine will explain this mystery by the fact that the older generation had already developed immunity due to previously suffering from influenza with similar strains.
In those days, doctors were almost powerless. They looked for various methods of treatment, but the only thing that somehow helped was blood transfusions from those who had already been ill and recovered.
1st half of the 20th century: discovery of the cause of the disease
Oddly enough, such disasters also entail important discoveries in the development of science. In 1933, research by British scientists: Patrick Laidlaw, Wilson Smith and Christopher Andrews led to the discovery of the virus. They conducted experiments on laboratory ferrets (and later mice) and proved that the culprit of the disease was not a bacterium, but a virus.
Sheffield professor Charles Stewart-Harris (author of classic textbooks on virology) took part in the development of the first vaccine.
In the USSR, virus research was led by the head. Department of Bacteriology at the Leningrad Institute of Epidemiology and Bacteriology named after Louis Pasteur - Anatoly Smorodintsev. He developed the first monovalent vaccine in 1936-1938. It contained only 1 strain of influenza, it was of the “live” type, i.e. contained a weakened virus, not fragments of it. In those days it was not possible to avoid frequent side effects, but nevertheless, even such a vaccine was a breakthrough step.
Another difficulty was that the virus mutates quickly, but scientists did not know this yet and the flu returned again and again.
Mid-20th century: the secret of the virus revealed
By this time, scientists had already identified 3 types of influenza virus. They are designated A, B and C.
1957 American virologist, Maurice Hilleman and his colleagues, when discovering the next type of influenza virus, discovered that people who survived the 1889-1890 pandemic were resistant to the new virus. Scientists have identified which proteins are responsible for the formation of immunity and have developed a suitable vaccine.
It turned out that the influenza virus consists of surface
and
internal
antigens. Surface antigens are variable, but internal antigens are constant.
Surface antigens
– this is:
hemagglutinin
(in the name of the strain it is designated H) – ensures the ability of the virus to attach to the cell;
neuraminidase
(denoted N) - is responsible for the ability of a viral particle to penetrate the host cell and for the ability of viral particles to exit the cell after reproduction.
Both hemagglutinin and neuraminidase have varieties that are usually numbered: H1, H2, H3..., N1, N2, N3... The high variability of the influenza virus type “A” is due to two properties: A) the possibility of gene exchange between different viruses during simultaneous infection of the same and the same cells, and B) gradual variability in the structure of N and H as a result of mutations (antigenic drift).
Combinations of different surface antigens determine different strains of the same A virus (H1N5, H1N1, etc.). One of the most recently identified H18N11 strains was found in 2013 in bats in Central America.
Internal antigens
make up the core (genome) of the virus in the form of
a ribonucleoprotein complex (nucleoprotein in complex with viral RNA)
and determine the type of virus (A, B or C).
When the secret of the virus was revealed, 40 million doses were produced, which helped reduce the number of deaths in the United States tenfold. In 1968, Hilleman was given another strain, the Hong Kong flu, and four months later another new vaccine was produced.
However, countries without a vaccine continued to suffer from the return of the virus, with outbreaks recorded in late 1969, 1970 and 1972. However, there were no such devastating consequences, because by this time there were antibiotics that saved from secondary infections; there was vaccination in a number of states; and many who have recovered have developed immunity.
Unusual solution
If, to protect against most vaccine-preventable infections (measles, diphtheria, polio, etc.), the same vaccine composition has been used for decades, and 1 course, and sometimes even one injection of the drug, is enough to develop full immunity in a person life, then in a situation with a constantly mutating flu, scientists had to look for a different way to make an effective vaccine.
The solution found is striking in its complexity and scale. Every year, for the flu season, we need to produce vaccines with a new composition! And to reduce the risk of errors, it is proposed to include in the vaccine not one strain, but a set (usually of three) of the most probable strains. A system was needed to monitor and forecast the circulation of the influenza virus in all countries on all continents.
In 1952, the WHO created the Global Influenza Surveillance and Response System (GISRS). Its work is to collect information about viruses from all over the world. The resulting data is entered into a single database and a special The commission makes a decision on the forecast of which influenza strains will actively circulate and can cause an epidemic in the coming season.A lot of factors are taken into account, including the aggressiveness of newly identified viruses, the similarity with previously circulating strains, and the presence of immunity in the population.
It was with the participation of this system that the possibility of effective influenza vaccine prevention became possible.
How does this happen
Every year in February, a WHO meeting takes place, at which, according to GISRS, recommendations are issued to manufacturers about the strains of influenza virus that should be included in the vaccine. At the end of February and beginning of March, the cultivation of strains begins. Almost all vaccine manufacturers use an old, proven technology for this: the influenza virus multiplies in chicken embryos. If the recommended strain is well cultivated, it is taken into production. Sometimes, due to poor growth of a particular type of virus, a well-growing analogue with a similar antigenic structure is urgently selected.
After this, the vaccine manufacturing process is activated at full capacity. Typically, it takes about 4 months to produce three (or four) strains, neutralize (in different ways for different types of vaccines), purification, quality control, mixing components and packaging. We recommend watching the vaccine production process in the video of our partners Sanofi Pasteur:
Next comes certification and logistics taking into account the “cold chain”. If everything goes smoothly, the first batches of the vaccine will arrive at medical organizations at the end of August. Typically, the main volumes become available in September-October, which makes it possible to vaccinate the population before the seasonal rise in incidence begins.
Use with other vaccines
Grippol plus can be combined with other live and inactivated vaccines, except BCG and BCG-M, and with inactivated vaccines of the preventive vaccination schedule for epidemic indications (with the exception of rabies). In this case, vaccines should be administered to different limbs.
In patients taking immunosuppressants, the effectiveness of vaccination may be reduced. It is recommended that such patients receive two doses of the vaccine at an interval of 3-4 weeks.
The end of the 20th – the beginning of the 21st centuries: by surprise
No matter how well GISRS works, unfortunately, sometimes the virus manages to break through contrary to scientists’ predictions. Humanity was taken by surprise by the outbreaks of the so-called “bird” and “swine” flu at the beginning of the 21st century. These strains, a recombination of human and animal viruses (birds and pigs), turned out to be completely new to human immunity and were not included in the WHO forecast.
In such rare cases, when unexpected mutations of influenza occur, vaccines are created on an emergency basis to prevent the infection from spreading widely, and are used separately, or the new strain is included in the seasonal vaccine.
In general, over the almost 70 years of existence of GISRS, the system has proven itself to be excellent and has shown the correctness of the adopted strategy for the prevention of influenza by adapting vaccine production to virus mutations.
To summarize the historical excursion, I would like to note the contribution of vaccination to protecting the population from influenza. According to the State report “On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2021”, the effectiveness of vaccination is clearly confirmed by the dynamics of influenza incidence, the level of which has decreased by almost 140 times since 1997 (from 5173.8 per 100 thousand population (with vaccination coverage of 4.9 million people in 1996) to 37.3 in 2021 (with vaccination coverage of 70.8 million people in 2021).
The graph clearly shows a decrease in incidence in direct proportion to the number of people vaccinated:
Drug interactions
Grippol® plus can be used simultaneously with inactivated and live vaccines of the National Preventive Vaccination Calendar (except for BCG and BCG-M) and inactivated vaccines of the preventive vaccination calendar for epidemic indications (except for rabies). The vaccine can be administered against the background of basic therapy for the underlying disease.
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Why doesn't the vaccine protect 100%?
Previously, we have already examined cases when vaccinated people can also get sick. Once again, we note that any vaccines do not provide a 100% guarantee. In the instructions for the drugs you will see efficiency indicators that are always above 80%, close to 95-99%.
Efficacy is influenced by the initial characteristics of the vaccine and the immune status of the individual. In the case of influenza, we described the additional risks and complexities associated with yearly forecasting and updating of strains.
Scientists have extensive experience in combating this elusive enemy; more than 2,000 serotypes of influenza viruses are known in the world. However, the risk of a completely new mutation always exists, and scientists cannot yet control this. Just like they cannot create a vaccine that would protect against influenza for life and 100%.
Whether you should get vaccinated when you are unsure of the Global Influenza Surveillance System forecasts is up to you. Perhaps the numbers will help you make a difficult choice: in Russia, among those sick with influenza A, 91.8% were unvaccinated, and among those who died, 100%.
How the vaccine works
Like any other, a flu shot is a drug containing weakened strains of viruses or their particles.
Since the influenza virus is constantly mutating, new combinations of strains are developed every year - this work is carried out by WHO specialists. When a vaccine is administered, the body begins the process of developing its own defenses. As a result, a person develops immunity that will help in the fight against the true influenza virus. “Protection” after a flu shot lasts 6–12 months, depending on the vaccine administered.
Modern vaccinations are inactivated drugs that have low reactogenicity, so the likelihood that the vaccine will cause a disease is extremely low. Rarely, general and local reactions occur in the form of fever up to 37–37.5 ° C, runny nose, dizziness, pain and redness at the injection site. In most cases, these conditions resolve on their own within 1–3 days after vaccination.
Please understand that vaccination does not provide a 100% guarantee that you will not get the flu. However, for those who are vaccinated, the disease is milder and the risk of complications is significantly lower.
Today: modern vaccines
The production of flu vaccines is generally a constant evolution. The first vaccines were live
.
Weakened viruses were used during production. Used as a nasal spray. Had a lot of side effects. Representative: Ultravac (Russia).
Then they began to use inactivated
vaccines.
The first of them contained, although purified, whole viruses ( whole virion vaccines
).
Their reactogenicity (ability to cause side effects) was very high. Representative: Grippovac (Russia).
Later, they began to produce vaccines with the destroyed virus ( split or split vaccines
).
They have fewer adverse reactions and fairly high immunogenicity. Such vaccines include all virion proteins of the virus (both surface and internal antigens), but due to high purification they do not contain viral lipids and chicken embryo proteins. Representatives: Ultrix (Russia), FLU-M (Russia), Vaxigrip (France), Fluarix (Germany), Fluvaxin (China).
The next class of vaccines is subunit
.
They contain only purified influenza virus surface antigens. Not only the virion and chicken embryo proteins were removed, but also internal antigens. Due to this, a significant reduction in reactogenicity was achieved. To increase the duration and intensity of immunity, manufacturers of subunit vaccines often add an adjuvant to the composition - a substance that enhances the immune response. Representatives: Influvac (Netherlands), Grippol plus (Russia), Sovigripp (Russia).
The last generation includes virosomal
vaccines in which surface antigens are presented in the form of virosomes (pseudoviral structures) that mimic the influenza virus, due to which the vaccine better “educates” the immune system of the person being vaccinated.
Representative: Inflexal V (Switzerland).
In addition to updating the technology for inactivation, assembly, and purification of influenza vaccines, other scientific work is underway to find ways to improve the quality, tolerability and effectiveness of influenza vaccines.
One of the ways to increase efficiency was the WHO recommendation to reorient production from 3-valent to 4-valent ones
vaccines.
Quadrivalent
vaccines contain proteins from four dangerous strains.
Examples: Ultrix Quadri (Russia), Grippol quadrivalent (Russia).
The Russian new generation vaccine “Ultrix Quadri” contains two strains A and B. Among the type A viruses there is H1N1 (similar to the culprit of “Spanish Flu 1918” and “Swine Flu 2009”). It is noteworthy that it was with this drug that Russian President Vladimir Putin, Health Minister Veronika Skvortsova and other members of the Government were vaccinated in 2021.
Influenza vaccine (inactivated)
Used in children over 6 months, adolescents and adults. Manufacturer – Russia.
Grippol® plus is an anti-influenza trivalent inactivated polymer-subunit vaccine. It is a protective antigen (hemagglutinin and neuraminidase) isolated from purified influenza viruses type A and B grown on chicken embryos, associated with a water-soluble high-molecular immunoadjuvant N-oxidized derivative of poly-1,4-ethylenepiperazine (azoximer bromide). The antigenic composition of the vaccine changes every year in accordance with the epidemic situation and WHO recommendations. The vaccine causes the formation of a high level of specific immunity against influenza. The protective effect after vaccination, as a rule, occurs after 8-12 days and lasts up to 12 months, incl. in elderly people. Protective titers of antibodies to influenza viruses after vaccination of people of different ages are determined in 75-95% of vaccinated people.
Who can't?
All influenza vaccines have absolute and temporary contraindications, which are indicated in the instructions for the drugs.
Vaccination is not carried out:
- If you are hypersensitive to chicken protein and have a severe allergic reaction to the vaccine. The key here is heavy.
- For an acute illness, a cold, which occurs with a temperature above 38°C.
- If the doctor has reason that the body’s immune response will not be formed. For example, if the patient is taking a therapy that suppresses the immune response.
- The live vaccine is not used in children under 3 years of age, pregnant women and people with impaired immunity.
Remember: The administered vaccine does not cause illness and does not contribute to a more severe course of influenza and other acute respiratory viral infections.
Contraindications to vaccination
Flu vaccines are safe drugs, but in some cases they cannot be used. Contraindications to the flu vaccine include:
- allergy to chicken egg white;
- allergy to components of previously administered vaccines;
- stage of exacerbation of a chronic disease;
- acute febrile condition.
The doctor decides whether to get a flu shot for mild acute respiratory infections, acute respiratory viral infections, and acute intestinal infections. As a rule, vaccination is possible immediately after the temperature normalizes. In the presence of chronic diseases, the vaccine is given in the remission stage.
Why is it especially important to get vaccinated during COVID-19?
If you get a flu shot, you will protect yourself from becoming infected with the dangerous flu viruses that WHO predicts today. The vaccine will not protect you from coronavirus. But those vaccinated against influenza have a better prognosis and a higher chance of coping with complications. More - because the layering of two infections at the same time will be excluded. In addition, both diseases begin with similar symptoms. Having a flu shot will allow your doctor to make a diagnosis faster, ruling out influenza, and prescribe treatment sooner.
When will foreign vaccines be purchased?
Currently, more than 20 influenza vaccines are registered in the state register of medicines, most of them produced by the Nacimbio holding, which is part of Rostec.
Of the foreign vaccines against influenza, two have been registered - “Vaxigripp” by the French Sanofi Pasteur and “Influvac” by the Dutch Abbott. Read on RBC Pro
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As explained by the analytical company DSM Group, since the influenza vaccine is produced by domestic companies within the framework of the “third wheel” provision, foreign companies cannot participate in tenders. In accordance with the rule, if at least two manufacturers from the EAEU countries enter the auction, a foreign manufacturer is not allowed to participate in the auction.
“At the same time, purchases for the national vaccination calendar, which specifically include influenza, are carried out within the framework of government orders. That is, the manufacturer makes the vaccine in the required quantity for a specific order,” the company adds.
The clinics surveyed by RBC now offer only domestic vaccines - Grippol Plus produced by Petrovax and Sovigripp. The Russian Ultrix Quadri is expected to arrive in mid-September. The last two vaccines are produced by Nacimbio.
As Medsi representative Alla Kanunnikova told RBC, imported Vaxigrip will appear no earlier than October, and there are no plans to use Influvac in the network’s clinics at all. The network of Mother and Child clinics also offers Russian flu vaccinations; foreign vaccines are expected to arrive there in November; clinic representative Dmitry Yakushkin found it difficult to specify which vaccines we are talking about.
Medical Director of the European Medical Center Evgeny Avetisov told RBC that, according to information from suppliers, Vaxigripp will appear no earlier than October; now one domestic vaccine, Sovigripp, is available in the clinic; another one, Ultrix, is expected later in September.
In the Be Healthy network of clinics, part of the group, it will be possible to get a flu shot from mid-September. As the general director of the network, Philip Mironovich, told RBC, the clinics will offer domestic “Grippol Plus” and “Ultrix”. “The imported vaccine will be available in Russia, presumably, no earlier than the end of October - the first ten days of November,” Mironovich told RBC, without explaining which foreign flu vaccine will be available.
The director of the Rassvet clinic, Alexey Paramonov, told RBC that the clinic expects delivery of Ultrix Quadri within a week, while the French Vaxigrip is expected only in mid-October.
In response to a request from RBC, the medical center explained that they are not vaccinating against influenza this year. After the publication of the text, a representative of the Meditsina JSC clinic also told RBC that currently flu vaccination can only be carried out with domestic vaccines. The clinic expects the foreign vaccine to arrive in October.
The flu vaccination should be done as early as September in order to minimize the risks of contracting coronavirus and influenza at the same time, says Leila Namazova-Baranova, President of the Union of Pediatricians of Russia. According to her, there is no point in waiting for a vaccine from a foreign country. At the same time, COVID-19 has not gone away; there are already publications describing patients who suffer from coronavirus at the same time as the flu. The more people who get vaccinated against flu now, the fewer such severe cases of simultaneous infections there will be,” the expert believes.
