Vaccine - what is it? Kinds and types of vaccines. On the shelves: vaccines - what, when, to whom

VACCINES(lat. vaccinus bovine) - preparations derived from bacteria, viruses and other microorganisms or their metabolic products and used for active immunization of people and animals for the specific prevention and treatment of infectious diseases.

Story

Even in ancient times, it was established that a contagious disease once transferred, for example, smallpox, bubonic plague, protects a person from re-disease. Subsequently, these observations developed into the doctrine of post-infectious immunity (see), i.e., increased specific resistance against the pathogen that occurs after the transfer of the infection caused by it.

It has long been observed that people who have had a mild illness become immune to it. Based on these observations, many peoples used artificial infection of healthy people with infectious material in the hope of a mild course of the disease. For example, for this purpose, the Chinese put dried and crushed smallpox scabs from sick people into the noses of healthy people. In India, crushed smallpox scabs were applied to the skin, previously rubbed to abrasions. In Georgia, for the same purpose, skin injections were made with needles moistened with smallpox pus. Artificial inoculation of smallpox (variolation) was also used in Europe, in particular in Russia, in the 18th century, when smallpox epidemics reached alarming proportions. However, this method of preventive vaccinations was not justified: along with mild forms of the disease, the vaccinated smallpox caused a serious illness in many, and the vaccinated themselves became sources of infection for others. Therefore, at the beginning of the 19th century. variolation was banned in European countries. African peoples continued to use it in the middle of the 19th century.

In connection with the spread of variolation, artificial inoculations of infectious material were also undertaken for some other infections: measles, scarlet fever, diphtheria, cholera, chicken pox. in Russia in the 18th century. D.S. Samoilovich suggested inoculating pus from plague buboes to persons in direct contact with the sick. These attempts to protect people from infectious diseases now retain only historical interest.

The introduction of modern V. into the human body or domestic animals aims to achieve the development of vaccination immunity, similar to post-infectious immunity, but with the exception of the risk of developing an infectious disease as a result of vaccinations (see Vaccination). For the first time, such V. for immunizing people against smallpox was obtained by the English physician E. Jenner using infectious material from cows (see Smallpox vaccination). The date of publication of the work of E. Jenner (1798) is considered the beginning of the development of vaccination, edges during the first half of the 19th century. has become widespread in most countries of the world.

Further development of the doctrine of V. is associated with the works of the founder of modern microbiology, L. Pasteur, who established the possibility of artificially weakening the virulence of pathogenic microbes (see Attenuation) and the use of such "attenuated" pathogens for safety vaccinations against chicken cholera, anthrax, agricultural . animals and rabies. Comparing his observations with the possibility of protecting people from natural smallpox by inoculating them with cowpox, discovered by E. Jenner, L. Pasteur created the doctrine of protective vaccinations, and suggested that the drugs used for this purpose, in honor of E. Jenner's discovery, be called V.

At subsequent stages in the development of the doctrine of vaccines, the work of Η was of great importance. F. Gamalei (1888), R. Pfeiffer and V. Kolle (1898), who showed the possibility of creating immunity not only by inoculation of weakened live microbes, but also by killed cultures of pathogens. Η. F. Gamalei also showed the fundamental possibility of immunization with chemical vaccines obtained by extracting immunizing fractions from killed microbes. Of great importance was the discovery by G. Ramon in 1923 of a new type of vaccinating preparations - toxoids.

Types of vaccines

The following types of vaccines are known: a) live; b) dead corpuscular; c) chemical; d) toxoids (see). Preparations intended for immunization against any one infectious disease are called monovaccines (eg, cholera or typhoid monovaccines). Divaccines are preparations for immunization against two infections (for example, against typhoid and paratyphoid B). Of great importance is the development of preparations intended for simultaneous vaccination against several infectious diseases. Such drugs, called associated V., greatly facilitate the organization of prophylactic vaccinations in anti-epidemic practice. An example of an associated vaccine is the DTP vaccine, which contains the antigen of the pertussis microbe, tetanus and diphtheria toxoids. With the right combination of components of associated V., they are able to create immunity against each infection, which is practically not inferior to the immunity obtained as a result of the use of individual monovaccines. In immunological practice, the term "polyvalent" V. is also used, when the drug is intended for vaccination against one infection, but includes several varieties (serological types) of the pathogen, for example, polyvalent V. against influenza or against leptospirosis. In contrast to the use of associated V. in the form of a single preparation, it is customary to call the combined vaccination the introduction of several V. simultaneously, but in different parts of the body of the vaccinated.

In order to increase the immunogenicity of V., especially chemical and toxoids, they are used in the form of preparations adsorbed on mineral colloids, most often on a gel of aluminum hydroxide or aluminum phosphate. The use of adsorbed V. prolongs the period of exposure to antigens (see) on the body of the vaccinated; in addition, adsorbents exhibit a nonspecific stimulating effect on immunogenesis (see Adjuvants). Adsorption of some chemical V. (eg, typhoid) helps to reduce their high reactogenicity.

Each of the above types of V. has its own characteristics, positive and negative properties.

Live vaccines

For the preparation of live V., hereditarily modified strains (mutants) of pathogenic microbes are used, which are deprived of the ability to cause a specific disease in the vaccinated, but retain the ability to multiply in the grafted organism, to populate the lymph, apparatus and internal organs to a greater or lesser extent, causing a latent, without clinical disease. , infectious process - vaccine infection. A vaccinated organism can react to a vaccine infection with a local inflammatory process (mainly with the cutaneous method of vaccination against smallpox, tularemia and other infections), and sometimes with a general short-term temperature reaction. Some reactive phenomena in this case can be detected in laboratory tests of the blood of vaccinated people. Vaccine infection, even if it proceeds without visible manifestations, entails a general restructuring of the body's reactivity, expressed in the development of specific immunity against the disease caused by pathogenic forms of the same type of microbe.

The severity and duration of post-vaccination immunity are different and depend not only on the quality of the live vaccine, but also on the immunological characteristics of individual infectious diseases. So, for example, smallpox, tularemia, yellow fever lead to the development of almost lifelong immunity in those who have been ill. In accordance with this, live V. against these diseases also have high immunizing properties. In contrast, it is difficult to count on obtaining highly immunogenic V., for example, against influenza or dysentery, when these diseases themselves do not create a sufficiently long and intense post-infection immunity.

Among other types of vaccine preparations, live vaccines are capable of creating the most pronounced post-vaccination immunity in the vaccinated, approaching post-infection immunity in intensity, but its duration is still shorter. For example, highly effective V. against smallpox and tularemia are able to ensure the resistance of a vaccinated person against infection for 5-7 years, but not for life. After vaccinations against influenza with the best samples of living V., pronounced immunity persists for the next 6-8 months; post-infection immunity against influenza drops sharply by one and a half to two years after the illness.

Vaccine strains for preparation of live V. are received in various ways. E. Jenner selected for vaccination against smallpox people a substrate containing vaccinia virus, which has complete antigenic similarity with the human smallpox virus, but is slightly virulent for humans. Brucellosis vaccine strain No. 19, belonging to the low pathogenic species Br., was selected in a similar way. abortus, which causes an asymptomatic infection in those vaccinated with the subsequent development of immunity to all types of Brucella, including the most dangerous species for humans, Br. melitensis. However, the selection of heterogeneous strains is relatively rare to find vaccine strains of the desired quality. More often it is necessary to resort to experimental changes in the properties of pathogenic microbes, seeking to deprive them of pathogenicity for humans or vaccinated domestic animals while maintaining immunogenicity associated with the antigenic usefulness of the vaccine strain and its ability to multiply in the vaccinated organism and cause an asymptomatic vaccine infection.

Methods of the directed change biol, properties of microbes for receiving vaccinal strains are various, but a common feature of these methods is more or less long-term cultivation of the causative agent outside the body of an animal sensitive to this infection. To speed up the process of variability, experimenters use certain effects on cultures of microbes. Thus, L. Pasteur and L. S. Tsenkovsky cultivated the pathogen in a nutrient medium at a temperature elevated against the optimum to obtain anthrax vaccine strains;

A. Calmette and Guerin (S. Guerin) for a long time, for 13 years, cultivated a tubercle bacillus in an environment with bile, resulting in the world-famous BCG vaccine strain (see). A similar method of long-term cultivation under adverse environmental conditions was used by N. A. Gaisky to obtain a highly immunogenic vaccine tularemia strain. Sometimes laboratory cultures of pathogenic microbes lose their pathogenicity "spontaneously", that is, under the influence of causes that are not taken into account by the experimenter. So the plague vaccine strain EV [Girard and Robie (G. Girard, J. Robie)], brucellosis vaccine strain No. 19 [Cotton and Buck (W. Cotton, J. Buck)], a weakly reactogenic variant of this strain No. 19 B A (P. A. Vershilov), used in the USSR for the vaccination of people.

Spontaneous loss of pathogenicity of microbial cultures is preceded by the appearance in their population of individual mutants with the quality of vaccine strains. Therefore, the method of selection of vaccine clones from laboratory cultures of pathogens, whose populations as a whole still remain pathogenic, is quite justified and promising. Such selection allowed H. N. Ginsburg to obtain an anthrax vaccine strain - a mutant of STI-1, suitable for vaccination not only in animals, but also in humans. A similar vaccine strain No. 3 was obtained by A. L. Tamarin, and R. A. Saltykov selected vaccine strain No. 53 from a pathogenic culture of the causative agent of tularemia.

Vaccine strains obtained by any method must be apathogenic, i.e., unable to cause a specific infectious disease in relation to humans and domestic animals undergoing prophylactic vaccination. But such strains can keep to some extent weakened virulence (see) for small laboratory animals. For example, tularemia and anthrax vaccine strains that are apathogenic to humans show reduced virulence when administered to white mice; some animals vaccinated with massive doses of live vaccine die. This property of live V. is not entirely appropriately called "residual virulence." The immunological activity of the vaccine strain is often associated with its presence.

To obtain vaccine strains of viruses, their long-term passaging in the body of the same animal species, sometimes not the natural hosts of this virus, is used. So, the rabies vaccine is prepared from a strain of a fixed virus (virus fixe) L. Pasteur, obtained from the street rabies virus, repeatedly passaged through the brain of a rabbit (see Anti-rabies vaccinations). As a result of this, the virulence of the virus for the rabbit increased sharply and the virulence for other animals, as well as for humans, decreased. In the same way, the yellow fever virus was converted into a vaccine strain by long intracerebral passages in mice (strains Dakar and 17D).

Infection of animals for a long period remained the only method of cultivating viruses. This was before the development of new methods for their cultivation. One of these methods was the method of culturing viruses on chicken embryos. The use of this method made it possible to adapt the highly attenuated strain 17D of the yellow fever virus to chicken embryos and to begin the widespread production of V. against this disease. The method of cultivation on chicken embryos also made it possible to obtain vaccine strains of influenza, mumps and other viruses pathogenic to humans and animals.

Even more significant achievements in obtaining vaccine strains of viruses became possible after the discovery of Enders, Weller and Robbins (J. Enders, T. Weller, F. Robbins, 1949), who proposed to grow the polio virus in tissue cultures, and the introduction of single-layer cell cultures into virology and the method of plaques [Dulbecco and Vogt (R. Dulbecco, M. Vogt, 1954)]. These openings have allowed to carry out selection of options of viruses and to receive pure clones - posterity of one or few virus particles possessing certain, hereditarily fixed biol, properties. Sabin (A. Sabin, 1954), who used these methods, managed to obtain mutants of the polio virus, characterized by reduced virulence, and bring vaccine strains suitable for mass production of live polio vaccine. In 1954, the same methods were used to culture the measles virus, to obtain a vaccine strain of this virus, and then to produce live measles B.

The cell culture method is successfully used both to obtain new vaccine strains of various viruses and to improve existing ones.

Another method for obtaining vaccine strains of viruses is a method based on the use of recombination (genetic crossing).

Thus, for example, it turned out to be possible to obtain a recombinant used as a vaccine strain of influenza A virus by interacting an avirulent influenza virus mutant containing hemagglutinin H2 and neuraminidase N2 and a virulent Hong Kong strain containing hemagglutinin H3 and neuraminidase N2. The resulting recombinant contained hemagglutinin H3 of the virulent Hong Kong virus and retained the mutant's avirulence.

Live bacterial, viral, and rickettsial infections have been the most widely studied and introduced into anti-epidemic practice in the Soviet Union in the last 20–25 years. Live V. are used in practice against tuberculosis, brucellosis, tularemia, anthrax, plague, smallpox, poliomyelitis, measles, yellow fever, influenza, tick-borne encephalitis, Q fever, and typhus. Live V. are being studied against dysentery, mumps, cholera, typhoid fever, and some other infectious diseases.

Methods of application of living V. are varied: subcutaneous (most V.), cutaneous or intradermal (V. against smallpox, tularemia, plague, brucellosis, anthrax, BCG), intranasal (flu vaccine); inhalation (vaccine against plague); oral or enteral (vaccine against polio, under development - against dysentery, typhoid, plague, some viral infections). Live V. during primary immunization is administered once, with the exception of V. against poliomyelitis, where repeated vaccination is associated with the introduction of vaccine strains of different types. In recent years, the method of mass vaccination using needleless (jet) injectors has been increasingly studied (see Needleless Injector).

The main value of living V. is their high immunogenicity. In a number of infections, especially dangerous ones (smallpox, yellow fever, plague, tularemia), live V. are the only effective type of V., since killed microbial bodies or chemical V. cannot reproduce sufficiently intense immunity against these diseases . The reactogenicity of live V. as a whole does not exceed the reactogenicity of other grafting preparations. During the many years of widespread use of live V. in the USSR, no cases of reversion of the virulent properties of the tested vaccine strains were observed.

Among the positive qualities of living V. are also the one-time use of them and the possibility of using a variety of methods of application.

The disadvantages of living V. include their relatively low stability in case of violation of the storage regime. The effectiveness of live V. is determined by the presence of live vaccine microbes in them, and the natural death of the latter reduces the activity of V. However, dry live V. produced, subject to the temperature regime of their storage (not higher than 8 °), are practically not inferior in terms of shelf life to other types of V. The disadvantage of some living V. (pox V., anti-rabies) is the possibility of neurological complications in individual vaccinated individuals (see Post-vaccination complications). These post-vaccination complications are very rare, and they can be largely avoided with strict adherence to the preparation technology and rules for the use of these V.

Killed vaccines

The killed V. receive an inactivation of pathogenic bacteria and viruses, using for this purpose various influences on cultures physical. or chem. character. According to the factor that ensures the inactivation of living microbes, heated V., formalin, acetone, alcohol, and phenol are prepared. Other methods of inactivation are also being studied, for example, by ultraviolet rays, gamma radiation, exposure to hydrogen peroxide and other chemicals. agents. To obtain killed V., highly pathogenic, antigenically complete strains of the corresponding types of pathogens are used.

In terms of their effectiveness, killed V., as a rule, are inferior to live ones, however, some of them have a sufficiently high immunogenicity, protecting those vaccinated from the disease or reducing the severity of the latter.

Since the inactivation of microbes by the above-mentioned effects is often accompanied by a significant decrease in the immunogenicity of V. due to the denaturation of antigens, numerous attempts have been made to use gentle methods of inactivation with heating of microbial cultures in the presence of sucrose, milk, and colloidal media. However, AD vaccines, gala vaccines, etc., obtained by such methods, did not enter into practice without showing significant advantages.

Unlike live V., most of which are applied by a single vaccination, killed V. require two or three vaccinations. So, for example, killed typhoid V. is injected subcutaneously twice with an interval of 25-30 days and the third, revaccinating, injection is carried out after 6-9 months. Vaccination against pertussis of killed V. is carried out three times, intramuscularly, with an interval of 30-40 days. Cholera V. is administered twice.

In the USSR, killed V. are used against typhoid fever and paratyphoid B, against cholera, whooping cough, leptospirosis, and tick-borne encephalitis. In foreign practice, dead V. is also used against influenza and poliomyelitis.

The main method of administration of killed V. are subcutaneous or intramuscular injections of the drug. Methods of enteral vaccination against typhoid and cholera are being studied.

The advantage of killed V. is the relative simplicity of their preparation, since this does not require specially and long-term studied vaccine strains, as well as relatively high storage stability. A significant disadvantage of these drugs is weak immunogenicity, the need for repeated injections in the course of vaccination, the limited methods of application of B.

Chemical vaccines

Chemical V. used for the prevention of infectious diseases do not quite correspond to their name accepted in practice, since they are not any chemically defined substance. These preparations are antigens or groups of antigens extracted from microbial cultures in one way or another and to some extent purified from ballast non-immunizing substances. In some cases, the extracted antigens are mainly bacterial endotoxins (typhoid chem. V.), obtained by processing cultures in ways similar to the method of obtaining the so-called. complete Boivin antigens. Other chemical V. represent the "protective antigens" produced by nek-ry microbes in the course of vital activity in an animal organism or in special nutrient media at the corresponding modes of cultivation (eg, a protective antigen of anthrax bacilli).

Of the chemical V. in the USSR, typhoid V. is used in combination with chemical. paratyphoid B vaccine or tetanus toxoid. For vaccination of children's contingents, another chemical is used. vaccine - Vi-antigen of typhoid microbes (see Vi-antigen).

In foreign practice, it has limited use for the immunization of some professional contingents of chemical. anthrax V., which is a protective antigen of anthrax bacilli obtained under special cultivation conditions and sorbed on an aluminum hydroxide gel. Double administration of this V. creates immunity in vaccinated people lasting 6-7 months. Repeated revaccinations lead to severe allergic reactions to vaccinations.

The listed V. are used for prophylaxis, that is, for the immunization of healthy people in order to develop immunity against a particular disease (see table). Some V. apply also at therapy hron, infectious diseases for the purpose of stimulation of development by an organism of more expressed specific immunity (see. Vaccine therapy ). Eg, at treatment hron, brucellosis apply killed V. (unlike live prophylactic V.). M. S. Margulis, v. D. Solovyov and A. K. Shubladze proposed therapeutic V. against multiple (multiple) sclerosis. An intermediate position between preventive and therapeutic V. is occupied by anti-rabies V., which is used to prevent rabies in persons infected and in the incubation period. With the medical purpose apply also an autovaccine (see), prepared by an inactivation of cultures of the microbes allocated from the patient.

Cooking Methods

V.'s preparation methods are various and are defined as biol, features of microbes and viruses from which V. prepare, and the level of technical equipment of vaccine production, a cut becomes more and more industrial in nature.

Bacterial bacteria are prepared by growing the appropriate strains on various, specially selected, liquid or solid (agar) nutrient media. Anaerobic microbes - producers of toxins, are grown in appropriate conditions. The technology for the production of many bacterial vaccines is increasingly moving away from laboratory conditions of cultivation in glass containers, using large reactors and cultivators, which make it possible to simultaneously obtain a microbial mass for thousands and tens of thousands of inoculation doses of the vaccine. The methods of concentration, purification and other methods of processing microbial mass are mechanized to a large extent. All living bacterial bacteria are produced in the USSR in the form of lyophilized preparations dried from a frozen state in a high vacuum.

Rickettsial live V. against Q-fever and typhus are obtained by culturing the appropriate vaccine strains in developing chicken embryos, followed by processing the obtained suspensions of yolk sacs and lyophilization of the drug.

Viral vaccines are prepared using the following methods: Production of viral vaccines on primary cell cultures of animal kidney tissue. In various countries, cultures of trypsinized kidney cells of monkeys (poliomyelitis B.), guinea pigs and dogs (B. against measles, rubella, and some other viral infections), and Syrian hamsters (anti-rabies B.) are used for the production of viral V..

Production of viral vaccines on substrates of avian origin. Chicken embryos and their cell cultures are successfully used in the production of a number of viral infections. So, on chicken embryos or in cell cultures of chicken embryos, V. is prepared against influenza, mumps, smallpox, yellow fever, measles, rubella, tick-borne and Japanese encephalitis, and other V. used in veterinary practice. Embryos and tissue cultures of other birds (for example, quails and ducks) are also suitable for the production of some viral V..

Production of viral vaccines on animals. Examples are the production of smallpox V. (on calves) and the production of anti-rabies V. (on sheep and suckling white rats).

Production of viral vaccines on human diploid cells. In a number of countries, in the production of viral infections (against poliomyelitis, measles, rubella, smallpox, rabies, and some other viral infections), the WI-38 strain of diploid cells obtained from the lung tissue of a human embryo is used. The main advantages of using diploid cells are: 1) a wide range of sensitivity of these cells to various viruses; 2) profitability of production of virus V.; 3) the absence of extraneous side viruses and other microorganisms in them; 4) standardization and stability of cell lines.

The efforts of researchers are aimed at breeding new strains of diploid cells, including props derived from animal tissues, in order to further develop and introduce into wide practice accessible, safe and economical methods for the production of viral B.

It should be emphasized that any V. proposed for widespread use must meet the requirements for the frequency and severity of adverse reactions and complications associated with vaccination. The importance of these requirements is recognized by WHO, which holds meetings of experts formulating all the requirements for biol, preparations and emphasizing that the safety of the drug is the main condition in the development of V.

V.'s production in the USSR is concentrated mainly in large in-ta vaccines and serums.

The quality of V., produced in the USSR, is controlled by both local control bodies at manufacturing institutes. and the State research institute of standardization and control of medical biol, preparations of them. L. A. Tarasevich. Production technology and control, as well as methods of V.'s application, are regulated by the Committee of Vaccines and Serums M3 of the USSR. Much attention is paid to the standardization of V.

Newly developed and offered for practice V. undergo a versatile approbation at the State Institute. Tarasevich, test materials are considered by the Committee of Vaccines and Serums, and when new V. are introduced into practice, the corresponding documentation for them is approved by M3 of the USSR.

In addition to a comprehensive study of new V. in animal experiments, after establishing the safety of the drug, it is studied in relation to reactogenicity and immunological efficacy in a limited experience of human immunization. The immunological efficacy of V. is evaluated by serological changes and skin allergic tests that occur in vaccinated people at certain times of observation. However, it should be borne in mind that these indicators by no means in all cases can serve as criteria for the actual immunogenicity of V., i.e., its ability to protect the vaccinated person from the corresponding infectious disease. Therefore, correlations between sero-allergic indicators in vaccinated people and the presence of actual post-vaccination immunity, which is revealed in animal experiments, are subject to deep and thorough study. The works of M.A. Morozov, L.A. Tarasevich, H.N. Ginsburg, N.N. Zhukov-Verezhnikov, N. A. Gaisky and B. Ya. Elbert, P. A. Vershilova, P. F. Zdrodovsky, A. A. Smorodintsev, V. D. Solovyov, M. P. Chumakov, O. G. Anjaparidze and others.

Bibliography: Bezdenezhnykh I. S., etc. Practical immunology, M., 1969; Ginsburg H. N. Live vaccines (History, elements of theory, practice), M., 1969; Zdrodovsky P. F. Problems of infection, immunity and allergies, M., 1969, bibliogr.; Kravchenko A. T., Saltykov R. A. and Rezepov F. F. A practical guide to the use of biological preparations, M., 1968, bibliogr.; Methodological guide for laboratory assessment of the quality of bacterial and viral preparations (Vaccines, toxoids, sera, bacteriophages and allergens), ed. S. G. Dzagurova et al., M., 1972; Prevention of infections by live vaccines, ed. M. I. Sokolova, M., 1960, bibliogr.; Rogozin I. I. and Belyakov V. D. Associated immunization and emergency prevention, D., 1968, bibliogr.

V. M. Zhdanov, S. G. Dzagurov, R. A. Saltykov.

Vaccines- immunobiological preparations intended for active immunoprophylaxis, that is, to create an active specific immunity of the body to a specific pathogen. Vaccination recognized by WHO as an ideal method for the prevention of human infectious diseases. High efficiency, simplicity, and the possibility of wide coverage of vaccinated persons in order to prevent the disease on a massive scale have brought active immunoprophylaxis into the category of state priorities in most countries of the world. A set of measures for vaccination includes the selection of persons to be vaccinated, the choice of a vaccine preparation and the determination of the scheme for its use, as well as (if necessary) monitoring the effectiveness, stopping possible pathological reactions and complications. As antigen in vaccine preparations are:

Whole microbial bodies (live or killed);
individual antigens of microorganisms (most often protective antigens);
microorganism toxins;
artificially created Ag microorganisms;
Ag obtained by genetic engineering.

Most vaccines divided into living, inactivated (killed, non-living), molecular (toxoids), genetically engineered and chemical; by the presence of a complete or incomplete set of antigens - into corpuscular and component, and by the ability to develop immunity to one or more pathogens - into mono- and associated.

Live vaccines

Live vaccines- preparations from attenuated (weakened) or genetically modified pathogenic microorganisms, as well as closely related microbes capable of inducing immunity to a pathogenic species (in the latter case, we are talking about the so-called divergent vaccines). Since everything live vaccines contain microbial bodies, they are classified as corpuscular vaccine preparations.

Immunization with a live vaccine leads to the development of the vaccination process, which occurs in the majority of those vaccinated without visible clinical manifestations. The main advantage of live vaccines is a completely preserved set of antigens of the pathogen, which ensures the development of long-term immunity even after a single immunization. Live vaccines also have a number of disadvantages. The most characteristic is the risk of developing a manifest infection as a result of a decrease in the attenuation of the vaccine strain. Similar phenomena are more typical for antiviral vaccines (for example, live polio vaccine can rarely cause poliomyelitis up to the development of spinal cord injury and paralysis).

Attenuated (attenuated) vaccines

Weakened ( attenuated) vaccines are made from microorganisms with reduced pathogenicity, but pronounced immunogenicity. The introduction of a vaccine strain into the body imitates the infectious process: the microorganism multiplies, causing the development of immune responses. The best known vaccines are for the prevention of anthrax, brucellosis, Q fever, and typhoid fever. However, most live vaccines- antiviral. The best known are the yellow fever vaccine, Sabin's polio vaccine, vaccines against influenza, measles, rubella, mumps, and adenovirus infections.

Divergent vaccines

As vaccine strains use microorganisms that are closely related to pathogens of infectious diseases. Ag of such microorganisms induce an immune response that is cross-directed to Ag of the pathogen. The best known and longest used vaccine is against smallpox (from the vaccinia virus) and BCG for the prevention of tuberculosis (from Mycobacterium bovine tuberculosis).

From WikiDol

COMPILERS: d.m.s., prof. M.A. Gorbunov, MD, prof. N.F. Nikityuk, Ph.D. G.A. Elshina, Ph.D. V.N. Ikoev, Ph.D. N.I. Lonskaya, Ph.D. n. K.M. Mefed, M.V. Solovieva, FSBI "NCESMP" of the Ministry of Health and Social Development of Russia, Center for Expertise and Control ILP

Vaccines- These are drugs obtained from live attenuated strains or killed cultures of microorganisms and their antigens, designed to create an active immune response in the body of vaccinated people and animals.

Among the various groups of medical biological preparations used for immunoprophylaxis and immunotherapy of infectious diseases, vaccines are the most effective means of preventing infectious diseases. The main active principle of each vaccine is an immunogen, similar in structure to the components of the pathogen responsible for the production of immunity.

Depending on the nature of the immunogen, vaccines are divided into:

• alive;

• killed (inactivated);

• split (split vaccines);

• subunit (chemical) vaccines;

• toxoids;

• recombinant;

• conjugated;

• virosomal;

• artificially adjuvanted vaccines;

• combined (associated polyvaccines).

Live vaccines

Live vaccines contain weakened living microorganisms (bacteria, viruses, rickettsiae) created on the basis of apathogenic pathogens, attenuated in artificial or natural conditions, by inactivation of genes or due to their mutations. Live vaccines create stable and long-term immunity, which is close to post-infection immunity in intensity, while a single injection of the drug is usually sufficient to develop immunity. The vaccine infectious process lasts for several weeks, is not accompanied by a clinical picture of the disease and leads to the formation of specific immunity.

Killed (inactivated) vaccines

Killed vaccines are prepared from inactivated virulent strains of bacteria and viruses and contain a killed whole microorganism, or components of the cell wall and other parts of the pathogen that have a complete set of necessary antigens. To inactivate pathogens, physical (temperature, radiation, UV rays) or chemical (alcohol, acetone, formaldehyde) methods are used, which ensure minimal damage to the structure of antigens. These vaccines have a lower immunological efficacy compared to live vaccines, so vaccination is carried out mainly in 2 or 3 doses and requires revaccination, which forms a fairly stable immunity, protecting the vaccinated from the disease or reducing its severity.

Split (split vaccines)

Vaccines contain destroyed inactivated virions, while retaining all the proteins of the virus (surface and internal). Due to the high purification from viral lipids and chick embryo proteins, the cultivation substrate, split vaccines have low reactogenicity. A high degree of specific safety and sufficient immunogenicity allow their use among children from 6 months of age and pregnant women.

Subunit (chemical) vaccines

Subunit Vaccines consist of individual microorganism antigens that can provide a reliable immune response in the vaccinated. To obtain protective antigens, various chemical methods are mainly used, followed by purification of the obtained material from ballast substances. The use of adjuvants enhances the effectiveness of vaccines. subunit (chemical) vaccines have a weak reactogenicity, can be administered in large doses and repeatedly, as well as used in various associations directed simultaneously against a number of infections.

Anatoxins

Anatoxins are prepared from microbial exotoxins that have lost their toxicity as a result of formaldehyde neutralization when heated, but retained their specific antigenic properties and the ability to cause the formation of antibodies (antitoxins). Purified from ballast substances and concentrated toxoid is sorbed on aluminum hydroxide. Anatoxins form antitoxic immunity, which is weaker than post-infection immunity.

Recombinant vaccines (vector)

Recombinant vaccines obtained by cloning of genes that provide the synthesis of the necessary antigens, the introduction of these genes into the vector and into producing cells (viruses, bacteria, fungi, etc.), then the cells are cultivated in vitro, the antigen is separated and purified. New technology has opened up broad prospects in the creation of vaccines. Recombinant vaccines are safe, quite effective, highly efficient technology is used to obtain them, they can be used to develop complex vaccines that create immunity against several infections simultaneously.

conjugate vaccines

Vaccines are conjugates of a polysaccharide obtained from infectious agents and a protein carrier (diphtheria or tetanus toxoid). Polysaccharides-antigens have weak immunogenicity and a weak ability to form immunological memory. binding of polysaccharides to a protein carrier, well recognized by the immune system, sharply enhances the immunogenic properties of the conjugate and causes protective immunity.

Virosome vaccines

Virosome vaccines contain an inactivated virosomal complex associated with highly purified protective antigens. Virosomes act as an antigen carrier and adjuvant, enhancing the immune response capable of inducing both humoral and cellular immunity.

Vaccines with artificial adjuvant

The principle of creating such vaccines is to use natural antigens of pathogens of infectious diseases and synthetic carriers. One of the options for such vaccines consists of a protein antigen of the virus and an artificial stimulant (for example, polyoxidonium), which has pronounced adjuvant (increasing the immunogenicity of antigens) properties.

Combined vaccines (associated polio vaccines)

These vaccines are a mixture of strains of different types of pathogens or their antigens to prevent two or more infections. When developing combined vaccines, the compatibility of not only antigenic components, but also their various additives (adjuvants, preservatives, stabilizers, etc.) is taken into account. These are vaccines of various types containing several components. Adverse reactions of the body to associated vaccines occur, as a rule, somewhat more often than to monovaccines, but they allow creating protection for the vaccinated in a short time against several infectious diseases.

An urgent task of modern vaccinology is the continuous improvement of vaccine preparations, approaches to their use, development of schemes, dosages, methods and timing of administration among different age groups.

Features of the vaccine production technology, as well as the mechanism of their action in the formation of immunity, must be taken into account when organizing and conducting all stages of clinical trials.

Prior to the commencement of clinical trials, the choice of territories and populations for the planned trials should be clearly justified. For this purpose, it is necessary to conduct a retrospective epidemiological analysis of an infectious disease in a certain area among the population included in the protocol of clinical trials. Based on the results of an epidemiological analysis, groups of volunteers are selected by age, gender, social characteristics, including territorial and seasonal fluctuations in incidence, which is essential when planning clinical trials and determining the safety and effectiveness of various types of vaccines.

Read also

• General provisions for conducting clinical trials of vaccines
• Clinical studies of inactivated influenza vaccines
• Features of conducting clinical trials of HIV/AIDS vaccines
• Features of conducting clinical trials of vaccines against especially dangerous infections
• Features of conducting clinical trials of vaccines against measles, mumps and rubella

The fear of vaccines is largely due to outdated ideas about vaccines. Of course, the general principles of their action have remained unchanged since the time of Edward Jenner, who in 1796 was the first to use smallpox vaccination. But medicine has come a long way since then.

So-called "live" vaccines, which use a weakened virus, are still used today. But this is only one of the varieties of remedies designed to prevent dangerous diseases. And every year - in particular, thanks to the achievements of genetic engineering - the arsenal is replenished with new types and even types of vaccines.

Live vaccines

Inactivated vaccines

Anatoxins

conjugate vaccines

Some bacteria have antigens that are poorly recognized by the immature immune system of infants. In particular, these are bacteria that cause such dangerous diseases as meningitis or pneumonia. Conjugate vaccines are designed to get around this problem. They use microorganisms that are well recognized by the child's immune system and contain antigens similar to those of the pathogen, for example, meningitis.

Subunit Vaccines

Effective and safe - they use only fragments of the antigen of a pathogenic microorganism, sufficient to ensure an adequate immune response of the body. May contain particles of the microbe itself (vaccines against Streptococcus pneumoniae and against meningococcus type A). Another option is recombinant subunit vaccines created using genetic engineering technology. For example, the hepatitis B vaccine is made by injecting some of the virus's genetic material into baker's yeast cells.

Recombinant vector vaccines

Vaccines (definition, the classification of which are discussed in this article) are immunological agents used as active immunoprophylaxis (otherwise, to form an active persistent immunity of the body to this particular pathogen). According to the WHO, vaccination is the best way to prevent infectious pathologies. Due to the high efficiency, simplicity of the method, the possibility of a wide coverage of the vaccinated population for the mass prevention of pathologies, immunoprophylaxis in many countries is classified as a state priority.

Vaccination

Vaccination is a special preventive measure aimed at protecting a child or an adult from certain pathologies, completely or significantly reducing their occurrence when they occur.

A similar effect is achieved by "training" the immune system. With the introduction of the drug, the body (more precisely, its immune system) fights the artificially introduced infection and "remembers" it. With repeated infection, immunity is activated much faster and completely destroys foreign agents.

The list of ongoing vaccination activities includes:

• selection of persons to be vaccinated;
• drug choice;
• formation of a scheme for the use of the vaccine;
• efficiency control;
• therapy (if necessary) of possible complications and pathological reactions.

Methods of vaccination

• Intradermal. An example is BCG. The introduction is made in the shoulder (its outer third). A similar method is also used to prevent tularemia, plague, brucellosis, anthrax, Q fever.
• Oral. It is used to prevent poliomyelitis and rabies. At the stages of development, oral remedies for influenza, measles, typhoid fever, meningococcal infection.
• Subcutaneous. With this method, a non-sorbed drug is injected into the subscapular or shoulder (outer surface at the border of the middle and upper thirds of the shoulder) area. Advantages: low allergenicity, ease of administration, immunity stability (both local and general).
• Aerosol. It is used as an emergency immunization. Highly effective are aerosol agents against brucellosis, influenza, tularemia, diphtheria, anthrax, whooping cough, plague, rubella, gas gangrene, tuberculosis, tetanus, typhoid fever, botulism, dysentery, mumps B.
• Intramuscular. Produced in the muscles of the thigh (in the upper anterolateral part of the quadriceps femoris). For example, DTP.

Modern classification of vaccines

There are several divisions of vaccine preparations.

1. Classification of funds in accordance with the generation:

• 1st generation (corpuscular vaccines). In turn, they are divided into attenuated (weakened live) and inactivated (killed) agents;
• 2nd generation: subunit (chemical) and neutralized exotoxins (anatoxins);
• 3rd generation is represented by recombinant and recombinant rabies vaccines;
• 4th generation (not yet included in practice), represented by plasmid DNA, synthetic peptides, plant vaccines, vaccines that contain MHC products and anti-idiotypic drugs.

2. Classification of vaccines (microbiology also divides them into several classes) by origin. By origin, vaccines are divided into:

• live, which are made from living but weakened microorganisms;
• killed, created on the basis of microorganisms inactivated in various ways;
• vaccines of chemical origin (based on highly purified antigens);
• vaccines that are created using biotechnological techniques, in turn, are divided into:

Synthetic vaccines based on oligosaccharides and oligopeptides;

DNA vaccines;

Genetically engineered vaccines created on the basis of products resulting from the synthesis of recombinant systems.

3. In accordance with the antigens included in the preparations, there is the following classification of vaccines (that is, as antigens in vaccines may be present):

• whole microbial cells (inactivated or live);
• individual components of microbial bodies (usually protective Ag);
• microbial toxins;
• synthetically created microbial Ag;
• Ag, which are obtained using genetic engineering techniques.

Depending on the ability to develop insensitivity to several or one agent:

• monovaccines;
• polyvaccines.

Classification of vaccines in accordance with the set of Ag:

• component;
• corpuscular.

Live vaccines

For the manufacture of such vaccines, weakened strains of infectious agents are used. Such vaccines have immunogenic properties, however, the onset of symptoms of the disease during immunization, as a rule, does not cause.

As a result of the penetration of a live vaccine into the body, stable cellular, secretory, humoral immunity is formed.

Pros and cons

Benefits (classification, application discussed in this article):

• minimum dosage required
• the possibility of a variety of methods of vaccination;
• rapid development of immunity;
• high efficiency;
• low price;
• immunogenicity as natural as possible;
• contains no preservatives;
• Under the influence of such vaccines, all types of immunity are activated.

Negative sides:

• if the patient has a weakened immune system with the introduction of a live vaccine, the development of the disease is possible;
• vaccines of this type are extremely sensitive to temperature changes, and therefore, when a "spoiled" live vaccine is introduced, negative reactions develop or the vaccine completely loses its properties;
• the impossibility of combining such vaccines with other vaccine preparations, due to the development of adverse reactions or loss of therapeutic efficacy.

Classification of live vaccines

There are the following types of live vaccines:

• Attenuated (weakened) vaccine preparations. They are produced from strains that have reduced pathogenicity, but pronounced immunogenicity. When a vaccine strain is introduced, a semblance of an infectious process develops in the body: infectious agents multiply, thereby causing the formation of immune responses. Among such vaccines, the best known are drugs for the prevention of typhoid fever, anthrax, Q fever and brucellosis. But still, the main part of live vaccines is antiviral drugs for adenovirus infections, yellow fever, Sabin (against polio), rubella, measles, influenza;
• Divergent vaccines. They are made on the basis of related pathogens of infectious pathologies strains. Their antigens provoke an immune response that is cross-directed to the antigens of the pathogen. An example of such vaccines is the smallpox vaccine, which is made on the basis of the vaccinia virus and BCG, on the basis of mycobacteria that cause bovine tuberculosis.

flu vaccines

Vaccines are the most effective way to prevent influenza. They are biologics that provide short-term resistance to influenza viruses.

Indications for such vaccination are:

• age 60 and older;
• bronchopulmonary chronic or cardiovascular pathologies;
• pregnancy (2-3 trimesters);
• outpatient and inpatient staff;
• persons permanently staying in closed groups (prisons, hostels, nursing homes, and so on);
• patients on inpatient or outpatient treatment that have hemoglobinopathy, immunosuppression, liver, kidney and metabolic disorders.

Varieties

The classification of influenza vaccines includes the following groups:

1. Live vaccines;
2. Vaccines inactivated:

• whole virus vaccines. Includes undestroyed highly purified inactivated virions;
• split (split vaccines). For example: Fluarix, Begrivak, Vaxigrip. Created on the basis of destroyed influenza virions (all proteins of the virus);

• subunit vaccines ("Agrippal", "Grippol", "Influvac") contain two viral surface proteins, neuraminidase and hemagglutinin, which provide the induction of an immune response in influenza. Other proteins of the virion, as well as the chick embryo, are absent, as they are eliminated during purification.