Anthrax vaccine. Anthrax vaccine Live anthrax vaccine for humans

INSTRUCTIONS
on the use of anthrax vaccine live dry
for subcutaneous and scarification use

The vaccine is a live spore of the anthrax vaccine strain STI, lyophilized in a 10% aqueous solution of sucrose, and has the appearance of a homogeneous porous mass of grayish-white or yellowish-white color.

IMMUNOLOGICAL PROPERTIES

Dry live anthrax vaccine after two-time use with an interval of 20...30 days causes the formation of intense immunity lasting up to 1 year.

PURPOSE

Specific prevention anthrax from the age of 14.

Vaccinations are subject to:

• persons working with live cultures of the causative agent of anthrax, with infected laboratory animals, or conducting research on materials contaminated with the causative agent of anthrax;
• persons slaughtering livestock, engaged in the procurement, collection, storage, transportation, processing and sale of raw materials of animal origin;
• persons performing the following work in anthrax-enzootic areas:
• public livestock maintenance;
• agricultural, agro- and drainage, construction and other work related to the excavation and movement of soil;
• procurement, fishing, geological, survey, expedition.

As planned, vaccination is carried out by the cutaneous method in the first quarter of the year, since the spring-summer season is the most dangerous in terms of anthrax infection in disadvantaged areas.

METHOD OF APPLICATION AND DOSAGE

The vaccine is used by cutaneous (scarification) and subcutaneous methods. It is advisable to carry out unscheduled vaccination subcutaneously.

Primary immunization is carried out twice with an interval of 20...30 days, revaccination is carried out once annually. For all vaccinations, the skin dose of the vaccine is 0.05 ml and contains 500 million spores, one subcutaneous dose of 0.5 ml contains 50 million spores.

Before use, each ampoule with the vaccine is carefully inspected. The vaccine cannot be used if the integrity of the ampoule is damaged, changes appearance dry and dissolved drug (foreign particles, unbroken lumps and flakes), absence of a label, after the expiration date, violation of storage conditions.

VACCINATION BY SUPERcutaneous (SCARIFICATION) METHOD

Immediately before use, the contents of the ampoule are resuspended in a sterile 30% aqueous solution of glycerol, which is added to the ampoule using a syringe with a needle for intramuscular administration. The volume of solvent is determined by the number of vaccination doses in the ampoule. Add 0.5 ml to an ampoule with 10 cutaneous doses, and 1.0 ml of solvent into an ampoule with 20 cutaneous doses. The ampoule is shaken until a homogeneous suspension is formed. The dissolution time of the vaccine should not exceed 5 minutes. The diluted vaccine from an opened ampoule, stored under aseptic conditions, can be used within 4 hours. The vaccination is carried out on the outer surface of the middle third of the shoulder. The grafting site is treated with alcohol or a mixture of alcohol and ether. The use of other disinfectant solutions is not permitted. After the alcohol and ether have evaporated, use a sterile tuberculin syringe with a thin and short needle (No. 0415), without touching the skin, apply one drop (0.025 ml) of the diluted vaccine to 2 places of future incisions at a distance of 3... 4 cm. Skin stretch slightly and with a sterile smallpox vaccination pen, make 2 parallel cuts 10 mm long through each drop of vaccine so that they do not bleed (blood should appear only in the form of small dewdrops). Using the flat side of a smallpox vaccination feather, rub the vaccine into the notches for 30 seconds and allow to dry for 5...10 minutes. A separate disposable feather is used for each person being vaccinated. It is prohibited to use needles, scalpels, etc. instead of feathers.

VACCINATION BY SUBCUTANEOUS METHOD

Immediately before use, the drug is resuspended in 1.0 ml of sterile 0.9% sodium chloride solution. The ampoule is shaken until a uniform suspension is formed. The contents of the ampoule are transferred with a sterile syringe into a sterile vial with 0.9% sodium chloride solution for injection. In the case of using an ampoule containing 200 subcutaneous vaccination doses, the suspension is transferred to a bottle with 99 ml, and containing 100 subcutaneous vaccination doses - into a bottle with 49 ml of solvent.

With the syringe method, the vaccine is injected into the area of ​​the lower corner of the shoulder blade. The skin at the injection site is treated with alcohol or a mixture of alcohol and ether. The vaccine in a volume of 0.5 ml is administered subcutaneously. A disposable syringe and needle are used for each person vaccinated. Before each vaccine collection, the vial is shaken. The injection site is lubricated with 5% tincture of iodine.

When using the vaccine by the subcutaneous needle-free method, the spore suspension is injected in a volume of 0.5 ml into the area of ​​the outer surface of the upper third of the arm using a needle-free injector with a protector, strictly following the instructions for their use. The vaccine injection site is treated before and after injection, as with the syringe method.

Unused vaccine, used vaccination disposable syringes and feathers are subject to mandatory inactivation by autoclaving at a temperature of (132±2)°C and a pressure of 2.0 kgf/m2 for 90 minutes.

Parts of the needleless injector that came into contact with the vaccine, after pretreatment, are immersed in a 6% solution of hydrogen peroxide with 0.5% detergent type “Progress” or “Astra” for 1 hour at a temperature not lower than 50 °C. The solution is used once.

Parts of the injector are sterilized by autoclaving at a temperature of (132±2) °C and a pressure of 2.0 kGs/m2 for 90 minutes.

REACTION TO INTRODUCTION

When applied cutaneously, the local reaction appears after 24...48 hours in the form of hyperemia, a slight infiltrate with the subsequent formation of a yellowish crust along the incisions. With syringe and needleless methods of administration, after 24...48 hours there may be slight pain, hyperemia at the injection site, and less often - an infiltrate with a diameter of up to 50 mm.

A general reaction during cutaneous and subcutaneous administration of the vaccine rarely occurs on the first day after vaccination and is manifested by malaise, headache and a slight increase in temperature. Sometimes there may be an increase in body temperature up to 38.5 ° C and a slight increase in regional lymph nodes.

CONTRAINDICATIONS

• Acute infectious and non-infectious diseases - vaccinations are carried out no earlier than 1 month after recovery (remission).
• Primary and secondary immunodeficiencies. When treating with steroids, antimetabolites, or radiotherapy, vaccinations are carried out no earlier than 6 months after the end of therapy.
• Malignant neoplasms and malignant blood diseases.
• Systemic diseases connective tissue.
• Common recurrent skin diseases.
• Diseases of the endocrine system.
• Pregnancy and lactation period.

In each individual case, for diseases not included in this list, vaccination is carried out only with the permission of the relevant medical specialist.

The interval between anthrax vaccination and the administration of other vaccines should be at least one month. In order to identify contraindications, the doctor (paramedic) on the day of vaccination conducts a survey and examination of the vaccinated with mandatory thermometry.

Vaccinations are carried out by the average medical staff under the guidance of a doctor.

RELEASE FORM

1.0 ml of vaccine in an ampoule containing 200 person-doses for subcutaneous or 20 person-doses for cutaneous vaccination with 1.5 ml of solvent for cutaneous use - 30% aqueous solution of glycerin.

1.0 ml of vaccine in an ampoule containing 100 person-doses for subcutaneous or 10 person-doses for cutaneous vaccination with 1.0 ml of solvent for cutaneous use - 30% aqueous solution of glycerol.

The package contains 5 ampoules of vaccine and 5 ampoules of solvent

STORAGE AND TRANSPORTATION CONDITIONS

The vaccine is stored and transported in accordance with SP 3. 3. 2. 028-95 at a temperature of 2 to 10 ° C. Transportation can also be carried out at a temperature not exceeding 25 °C for no more than 20 days.

BEST BEFORE DATE

Vaccine produced under vacuum - 4 years; release without vacuum - 3 years.

Passive immunization. In the new millennium, when the threat of bioterrorism has taken on obvious shape, emergency specific prevention of anthrax has become particularly relevant. To prevent the mass spread of infection in cases of suspected or actual bioterrorist acts, passive transfer of specific antibodies has increasingly begun to be proposed. The principle of passive immunization using immune sera has been used for more than 100 years. Modern hybridoma technologies make it possible to obtain highly specific antibodies to individual epitopes of immunogenic protein molecules. In the USSR, for the purpose of emergency prevention of anthrax, specific anthrax immunoglobulin was used, administered intramuscularly in a dose of 20-80 ml.

However, its use was discontinued due to the very common occurrence of severe allergic reactions.

A surge of interest in the creation of means of emergency specific prevention of anthrax arose after the tragic events of 2001. Experiments on laboratory animals showed that intraperitoneal injections of antiserum to the protective antigen B. anthracis 24 hours after the onset of anthrax infection save 90% of infected biomodels from death. However, sera obtained by immunization with a lethal factor or the B. anthracis strain Sterne 34F2 are less effective. Monoclonal antibodies to a protective antigen and a lethal factor were obtained from the serum of people vaccinated with a licensed chemical anthrax vaccine. It has been established that a single passive immunization of laboratory animals with them, carried out several hours before peritoneal infection with the anthrax pathogen, prevents the development of a lethal infectious process in 100% of cases. A risk factor when using sera from vaccinated people is the theoretically possible possibility of infection with pathogenic viruses.

Not only antibodies to the protective antigen have a preventive effect. Passive immunization with monoclonal antibodies to the polyglutamine capsule protected 90% of mice from developing pulmonary anthrax. Similarly, antispore IgG had a protective effect during peritoneal infection with a virulent culture of the anthrax pathogen. Injecting mice with monoclonal antibodies to the lethal factor 24 hours before the injection of the lethal toxin effectively protected the animals from death. Passive immunization is in demand when emergency specific prevention of an infectious disease is necessary. To create intense and long-lasting immunity, vaccines containing or producing immunogenic antigens of a pathogenic microorganism are used.

Active immunization. HISTORY OF THE CREATION OF ANTHRAX VACCINES. In the history of the creation of drugs that protect against infection with the anthrax pathogen, four fundamentally different periods are distinguished.
Period 1. Attenuation of natural strains of B. anthracis under certain growing conditions.
Period 2. Selection of clones that have lost the ability to synthesize capsules.
Period 3. Isolation of individual protective antigens of attenuated strains of B. anthracis and the creation of chemical vaccines based on them.
Period 4. Directed design of safe and effective vaccines taking into account the genetic and molecular biological basis of the immunogenicity and virulence of the anthrax pathogen.

The first attempts to develop a vaccine against anthrax were made by L. Pasteur, who in 1881 attenuated the virulent strain of B. anthracis through long-term passaging in a liquid nutrient medium at a temperature of 43 °C. Weakened isolates isolated on the 12th and 24th days of cultivation were subsequently named the 2nd and 1st Pasteur vaccines, respectively. Using the same principle of attenuation, Professor of Kharkov University L.S. Tsenkovsky and professor of the Kazan Veterinary Institute I.N. Lange selected similar strains of B. anthracis, characterized by reduced virulence. In Russia, live vaccines have been widely used since 1885. The effect of mass immunization of farm animals was impressive and encouraging at that time. From a modern point of view, vaccines obtained empirically are characterized by heterogeneity of population composition and retain the ability to produce a capsule, as a result of which they have high reactogenicity and residual virulence, which is expressed in unstable vaccination results, side effects and even deaths.

The next stage in the creation of anthrax vaccines is the selection of clones that do not form a capsule under in vivo conditions or reproduce them in vitro. The noncapsular strain of B. anthracis was first isolated by N. Stamatin in 1934. Isolate B. anthracis 1190-R was selected as a result of long-term cultivation of a virulent strain on citrated horse blood. Experiments on rabbits and sheep showed its high immunogenicity. Since 1950, all farm animals sensitive to anthrax have been vaccinated with this vaccine in Romania.
In the USA in 1937, M. Sterne obtained a capsule-deprived strain of B. anthracis Sterne 34F2 by cultivating a virulent culture of the anthrax pathogen isolated in South Africa on 50% serum agar in an atmosphere of 30% carbon dioxide. While maintaining immunogenic properties, the strain turned out to be avirulent for animals. The live vaccine based on B. anthracis Sterne 34F2 is recommended by WHO for veterinary practice and is currently used in many countries around the world. Since 1939, derivatives of the anthrax bacterium that have lost their capsule have also been obtained in Japan, England and India.

In the USSR, the non-capsular strain was first isolated by N.N. Ginsburg in 1940. The non-capsule-forming variant was selected from the population of the virulent strain of B. anthracis “Krasnaya Niva” (isolated in 1934 from a horse at the Oryol biofactory) when grown on coagulated horse serum. Based on the resulting strain, the vaccine preparation STI-1 was developed, presented in 1941 to the State Commission for testing. Due to its high protective ability and relative harmlessness, the B. anthracis STI-1 vaccine began to be widely used in our country for immunization of animals already in 1942. Under the leadership of N.N. Ginsburg developed a technology for the hardware production of anthrax vaccine, methods for controlling its quality, as well as methods for immunizing laboratory animals. The harmlessness and weak reactogenicity of the B. anthracis STI-1 vaccine for the population were first demonstrated in 1943. The very next year it was used to eliminate outbreaks of anthrax among troops in Iran and Romania. Since 1951, the drug B. anthracis STI-1 has been recommended by the Ministry of Health for immunization of people at risk.

In 1946-1949. S.G. Kolesov et al. isolated a capsular variant of the virulent B. anthracis strain Shuya-2. The highly immunogenic strain served as the basis for the creation in 1951-1952. anthrax vaccine "GNKI". In 1953-1955. it was put into practice. Currently, the GNKI vaccine has been discontinued. From 1984-1986 The B. anthracis-55 vaccine, obtained on the basis of a natural non-capsular isolate, which was isolated from the body of a pig infected with the anthrax pathogen, has been adopted into the practice of veterinary medicine. In 1984, commission tests of the drug on sheep were carried out on farms in the Vladimir region. A single immunization with the B. anthracis-55 strain ensured the development of stable immunity lasting at least 18 months. No serious post-vaccination complications were identified. The risk of side effects when using live vaccines dictated the need to find safer methods of vaccination. Numerous works carried out at this stage of the creation of immunological drugs are devoted to the preparative isolation, purification and assessment of the protective properties of individual antigens of the anthrax pathogen. Of no small importance was the study of the conditions for the synthesis of the protective factor and its stabilization.

Anthrax antigen, which has protective properties, was first obtained by G. Gladstone in 1946-1948. from the supernatant of a B. anthracis culture grown in liquid whey medium supplemented with 0.5% sodium bicarbonate. In 1954, they proposed a technology for the scaled production of protective antigen, as well as synthetic and semi-synthetic media for its optimal production. The sterile culture filtrate was adsorbed under certain conditions onto a 0.1% aluminum hydroxide gel. In the same year, the reactogenicity and immunological effectiveness of a potential chemical anthrax vaccine were examined in human trials. A large-scale trial of the anthrax chemical vaccine was carried out in 1962. General reactions were mild and were recorded in only 0.2% of those vaccinated. The incidence and severity of local reactions increased with increasing number of vaccinations. After the 5th injection of the drug, they were detected in 35% of vaccinated people, including in 2.8% these reactions were significantly pronounced. Technologies for isolating and purifying the protective antigen of B. anthracis were also developed by English scientists.

In the USSR, research into anthrax protective antigen in order to create specific prophylactic drugs carried out under the guidance of N.I. Alexandrova. In 1961-1963. A drug with protective properties was isolated from the cultural filtrate of the vaccine strain B. anthracis STI-1. To obtain it, we used hardware deep cultivation in a milk-peptone medium with sodium bicarbonate and other mineral salts. In experiments, double or triple subcutaneous immunization of white mice, guinea pigs, rabbits, sheep and monkeys were not inferior in effectiveness to single subcutaneous vaccination with the live B. anthracis STI-1 vaccine. In 1963, received by N.I. Alexandrov et al. the chemical vaccine was tested on volunteers. The drug was administered subcutaneously twice with an interval of 17 days. In all cases, after the 1st vaccination, it was noted general reactions.

In 1976-1982. Research on the creation of a domestic chemical vaccine was continued by a group of employees of the Research Institute of Bacterial Vaccine Preparations of the USSR Ministry of Defense under the leadership of M.I. Derbina. They developed a nutrient medium, a technology for obtaining a protective antigen in laboratory and experimental production conditions, methods for its purification and concentration, methods for determining the activity of a protective antigen in vitro and the immunological effectiveness of the drug. The experimental chemical vaccine obtained by the team of authors, previously characterized using biomodels, final stage tested on volunteers. People were immunized subcutaneously twice with an interval of 21 days. No side effects were detected after the 1st injection of the drug. After repeated use on the 1st day, two people experienced slight pain at the application site. Based on the results of the tests, regulatory and technical documentation for the chemical anthrax vaccine was developed, passed the procedure approval by the USSR Ministry of Health. Currently, a chemical vaccine is not produced in Russia.

A combined immunization regimen was used. The effect of using a combination of a protective antigen preparation with a live vaccine was superior to the effect of each component separately. No complications were noted after vaccination. In 1970 E.N. Shlyakhov used the same approach to create effective protection against infection with the anthrax pathogen. The immunization regimen included a double injection of a protective antigen preparation with an interval of 7 days and a single dose of the live B. anthracis STI-1 vaccine. Combined vaccination, in comparison with immunization with single drugs, provided higher values ​​of immunity indices and did not cause the development of pathological processes in the body of experimental animals. In addition, it made it possible to reduce the dosage of the components used. In 1998, a combined anthrax vaccine was developed in Russia, which is a combination of a cell-free preparation of a protective antigen adsorbed on an aluminum hydroxide gel and spores of the vaccine strain B. anthracis STI-1.

LIVE VACCINES. Currently, live spore vaccine is used all over the world for the immunization of anthrax in farm animals. Abroad, in most cases these are spores of the capsular strain of B. anthracis Sterne 34F2, with or without saponin as an adjuvant. This vaccine is produced in the USA, Great Britain, France, the Netherlands, Hungary, Greece, Turkey, Pakistan, China, North Korea, Japan, India, Indonesia, Australia, Colombia, Ethiopia, Nepal, Uruguay, Kenya and Zambia. In Russia specific prevention anthrax in animals is carried out with preparations containing spores of non-capsular strains B. anthracis-55 or B. anthracis STI-1, in Romania - B. anthracis-1190"R and in Italy - B. anthracis Pasteur. Veterinary vaccine V. al £/ggas/5-55-VNIIVViM is produced by the All-Union Research Institute of Veterinary Virology and Microbiology.The drug is available in liquid, liquid concentrated and lyophilized forms.

A live vaccine effectively protects against infection by a pathogenic microorganism. A single subcutaneous administration of one dose of veterinary vaccine based on the B. anthracis strain Sterne 34F2 causes the formation of specific resistance lasting at least a year in animals susceptible to anthrax. At the same time live vaccine often associated with residual virulence and reactogenicity. Thus, the B. anthracis strain Sterne 34P2 may be virulent for some animal species (goats and llamas). Side effects associated with the effect on the human or animal body of toxic waste products of vaccine strains.

The use of live spore vaccine to vaccinate populations at risk of anthrax infection is regulated in countries former USSR(strain B. anthracis STI-1) and China (strain B anthracis-A16R). In most other countries, immunization of anthrax in humans is carried out with a chemical vaccine manufactured in the USA or Great Britain.
In the USSR, starting from 1953, the production of live anthrax vaccine was carried out at the Tbilisi Research Institute of Vaccines and Serums. To obtain spores, the bacterial culture of B. anthracis STI-1 was grown on a solid nutrient medium. Currently, in Russia they use an anthrax live dry vaccine based on the B. anthracis strain STI-1, produced by the Federal State Institution “48th Central Research Institute of the Ministry of Defense of Russia” (Kirov) and in the branch of the Federal State Institution “48th Central Research Institute of the Ministry of Defense Russia" "CVTP BZ" (Ekaterinburg). The technological process of vaccine production includes deep cultivation of the microorganism in a liquid nutrient medium. This drug, compared to the Tbilisi Research Institute vaccine, contains fewer ballast substances and is standardized.

Live anthrax vaccine is produced in the form of a lyophilisate, from which a suspension is prepared for subcutaneous administration and cutaneous scarification application. Received for vaccine registration certificate. Testing of sample batches of the drug demonstrates its full compliance with the requirements regulatory documentation. The vaccine does not contain foreign microorganisms and fungi and is specifically safe for laboratory animals (rabbits). The total concentration of spores in the preparation is 4.5-10.0x109. The concentration of living spores is 57-82% (the norm is at least 40%). The immunity index for guinea pigs has an average value of 1.6x106 (the norm is at least 104). Every year, institutions of the Ministry of Health and social development, as well as the Ministry of Defense, 30,000-50,000 sets of live anthrax vaccine are being supplied.

Previously, the issue of the frequency of vaccination of people with live anthrax vaccine was discussed. It was noted that after a single subcutaneous application of the STI-1 vaccine, adaptive immunity was detected after 1 month only in 50-60% of vaccinated people; it persisted for up to 3 months in 28-32% of vaccinated people, and up to 5 months in only 15%. Revaccination carried out every other year also does not provide a high level of protection. At the same time, double immunization with the same drug causes the development of more intense immunity, which is detected after 1 month in 77.7-87.5% of vaccinated people. The effectiveness of revaccination also increases. A study of indirect immunological tests 3, 6 and 12 months after double immunization with live spore vaccine revealed, respectively, 75-80, 55-60 and 43-48% of individuals with a high level of immunity. In this regard, a vaccination scheme has been proposed, including an initial two-time use of a live vaccine and subsequent annual revaccinations.

CHEMICAL VACCINES. The American chemical anthrax vaccine AVA is manufactured by BioPort Corporation by adsorption on aluminum hydroxide of the components of the cultural filtrate of the B. anthracis strain-V770-NR1-R - a protease-negative derivative of the B. anthracis strain Sterne 34F2.

The drug contains 5-20 μg/ml of total protein, the protective antigen accounts for approximately 35%. The presence of impurities of edematous and lethal factors in the American chemical vaccine preparation varies from lot to lot. The effectiveness and safety of the drug are confirmed by regulatory documents of the Quality Control Department food products And medicines USA. The vaccine is administered subcutaneously in 0.5 ml doses. The primary immunization complex includes three injections with repeats after 2 and 4 weeks. Booster vaccinations are carried out 6, 12 and 18 months after the 1st vaccination. In addition, annual booster vaccination is recommended for individuals at risk of anthrax infection to maintain immunity. The effectiveness of such a vaccination schedule, according to the results of various studies, is in the range of 92.5-95%.

Immunized guinea pigs were reliably protected during both intramuscular and aerosol infection with virulent strains of B. anthracis. Tests of the American chemical vaccine on the rhesus macaque model also demonstrated its protective ability when infected with an aerosol containing lethal doses of anthrax spores.

When using the AVA vaccine, 2.8% of immunized people experience moderate local reactions - swelling and infiltration measuring 3-12 cm. In approximately 20% of cases, less pronounced local manifestations are detected in the form of hyperemia, edema and infiltration measuring less than 3 cm. B clinical studies, conducted in 1996-1999. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) involved 28 volunteers. Each of them was administered a licensed chemical vaccine subcutaneously according to a prescribed vaccination schedule. The condition was assessed during the first 30 minutes and 1-3 days, 1 week and 1 month after vaccination. In four volunteers, erythema was detected within 30 minutes after subcutaneous injection, headache and/or increased temperature. In the longer term, in 4% of cases, general reactions were observed, including malaise, headache, myalgia, fever, difficulty breathing, nausea or vomiting. Local reactions (redness, infiltration, pain at the injection site, itching and swelling) were recorded more often in women. All the described phenomena stopped quite quickly without symptomatic treatment.

A USAMRIID analysis of the health status of 1,583 workers receiving preventive vaccinations American chemical vaccine (of which 273 people received 10 doses or more, 46 people received 20 doses or more), showed that in women and people over 40 years of age, local and general reactions to vaccination occur more often. Local symptoms occurred in 3.6% of cases and systemic manifestations in 1% of cases of AVA vaccine.

The toxic effect of chemical vaccines is associated with the content of impurities of edematous and lethal factors, as well as some other products of cell activity. Cases of necrosis in the area of ​​injection of a chemical vaccine have been reported. Due to the complexity of the vaccination schedule and the frequent development of local and systemic reactions, studies are being conducted to evaluate the protectiveness and safety of the vaccine by reducing the frequency and changing the route of administration. Three times subcutaneous vaccination was proposed with an interval of 2 weeks and revaccination after 6 months and then annually. According to another scheme, the vaccine was administered intramuscularly twice with an interval of 4 weeks. A comparative examination of individuals immunized according to the standard and alternative schedules did not reveal statistically significant differences between the levels of IgG antibodies to the protective antigen. At intramuscular injection vaccines were less likely to cause local adverse reactions.

In England, to immunize people against anthrax, a protein preparation is used, obtained from the cultural filtrate of the B. anthracis strain Sterne 34F2, grown in a nutrient medium with the addition of casamino acids (Porton Down, Salisbury, Wiltshire). Aluminum hydroxide is used as an adjuvant. The vaccine is administered intramuscularly four times, 0.5 ml, with intervals between the first three vaccinations of 3 weeks, and between the 3rd and 4th (booster) - 7.5 months. Revaccination is carried out annually. A chemical vaccine ensures the development of immunity in a more early dates than a living spore. The titer of specific antibodies reaches its maximum values ​​at the 2nd week after immunization, then it gradually decreases and reaches the “pre-booster” threshold by the 12th week. Despite the fact that antibody titers to the protective antigen during vaccination chemicals significantly higher than when using live vaccines, the latter still provide more effective protection against infection with the anthrax pathogen. This indicates the participation in the immune process not only of the protective antigen, but also of other antigens. At the same time, the study of the protective ability of attenuated and recombinant vaccine strains with different production of protective antigen revealed that the severity of their protective effect correlates with the level of formation of the protective antigen and the magnitude of antibody titers to it in ELISA. Interesting experimental data show that antibodies to a protective antigen, induced by the introduction of a chemical vaccine, suppress the germination of spores and stimulate their absorption by phagocytes. The general advantages of chemical vaccines include the possibility of standardization and complex use of antigens.

The main disadvantage of a cell-free antigenic drug is the relatively low intensity of the immunity it creates. Anthrax protective antigen primarily determines the development humoral immunity(IgG and IgM), while a cellular immune response is also necessary to form complete protection against infection with the anthrax pathogen. In addition, there are strains of the anthrax pathogen that can overcome specific immunity in guinea pigs immunized with a chemical vaccine. The US-licensed AVA vaccine protects guinea pigs to a greater extent from infection with B. anthracis Vollum 1B spores than with B. anthracis Ames spores.

COMBINED VACCINES. The production of anthrax combined vaccine is licensed in the Federal State Institution “48th Central Research Institute of the Ministry of Defense of Russia” (Kirov) and in the Central Military Technologies Center BZ - a branch of the Federal State Institution “48th Central Research Institute of the Ministry of Defense of Russia” (Ekaterinburg). The vaccine, consisting of a protective antigen preparation adsorbed on an aluminum hydroxide gel and spores of the vaccine strain B. anthracis STI-1, is produced in the form of a lyophilisate, from which a suspension is prepared for subcutaneous administration. Testing of sample batches of the vaccine showed its full compliance with the requirements of regulatory documentation. The vaccine of all series did not contain foreign microflora and was specifically safe for laboratory animals (rabbits). The concentration of live spores was at an average level of 62.6%; the antigenic activity of the drug was 50 EA/ml (activity units in ml), the completeness of antigen sorption was 25 EA/ml. All indicators were within the established standards. Currently, a registration certificate for the anthrax combination vaccine is being issued.

The combined vaccine developed in the Russian Federation provides protection against infection with the anthrax pathogen in 90-100% of cases, including when used in combination with antibiotics. Intense immunity with a regulated single use of the combined vaccine is formed already by the 7-10th day, while with two- and three-time use of live and chemical vaccines - after 1-1.5 months, respectively. In preclinical trials of the combination drug, no significant differences were found in terms of safety and reactogenicity compared to the live vaccine. In a number of cases, the level of protection of experimental animals exceeded the effect of using each of its components separately. During the primary single subcutaneous immunization of people with the combined vaccine, intense immunity was formed in more than 80% of those vaccinated, which persisted for high level within 8 months. In approximately 5% of vaccinated individuals with active antibody production, these titers persisted for 1.5 years, and the index of preventive properties of sera was 0.4 or higher. The donor's age, blood type and Rh factor did not affect the activity of the humoral response. 8 months after vaccination with the dry combination vaccine, active formation of antibodies to the protective antigen (1:800, according to ELISA results) was detected in 40%, a weak immune response (1:100) was recorded in 15% of individuals. When vaccinated with live anthrax vaccine, completely different dynamics were observed: an antibody titer of 1:800 was not detected in any of the donors, in 20% it was 1:400, and in 80% it was 1:100 or lower. Low sensitization of the body of people vaccinated once with the combined anthrax vaccine was noted.

Anthrax is an infectious disease that has a very severe course. Most often it develops in the form of a cutaneous form (the formation of carbuncles on the surface of the skin). To prevent its occurrence, a certain group of people must be vaccinated with anthrax vaccine.

Name of the vaccine, its composition and release form

Live anthrax vaccine. Dosage form- lyophilisate for preparing a suspension for scarification application or subcutaneous administration. The vaccine consists of:

• Lyophilized suspension of live spores of the bacillus anthracis strain STI-1 (500 million spores in 1 ampoule).
• Purified anthrax antigen (350 ID50).
• Aluminum hydroxide gel (no more than 25 mg in 1 ampoule).
• Stabilizer - aqueous solution of sucrose 10%.

Also included with the vaccine is a solvent - a solution of glycerol (glycerol) 10%. It has the following release forms:

• 100 subcutaneous (10 cutaneous) vaccination doses - 5 ampoules, complete with solvent (5 ampoules of 1 ml each) in a cardboard box.
• 200 subcutaneous (20 cutaneous) vaccination doses - 5 ampoules, complete with solvent (5 ampoules of 1 ml each) in a cardboard box.

Vaccine characteristics

The anthrax vaccine is a vacuum-dried suspension of spores of the STI-1 strain. For production, a persistent type of anthrax bacilli is used, which are incapable of causing disease in humans. After a two-time administration (with an interval of 20-30 days), the vaccine forms stable specific immunity. The formation of intense immunity begins 7 days after administration and lasts up to a year. Persons over 14 years of age are subject to vaccination. Revaccination is carried out every year, with an interval of one year, only when indicated.

Indications for vaccine administration

Vaccinations to prevent the occurrence of anthrax are carried out routinely or according to epidemic indications. The following persons are subject to routine vaccination:

• Those who slaughter livestock, transport, collect and store, process and sell any raw materials of animal origin.
• Working in laboratory conditions with live cultures of anthrax bacilli. Conduct research on infected laboratory animals and materials.

Vaccination is carried out in the first quarter of each year. According to epidemic indications, people who:

• They are engaged in construction, agrotechnical, and economic work in enzootic areas.
• Serving livestock.
• They are engaged in expeditions, geological and survey work.

Vaccination is carried out only according to strict indications. In each individual case, vaccination is carried out only with the permission of the appropriate specialist.

Method of administration of the vaccine and dose

The vaccine is administered by cutaneous and subcutaneous routes of administration. Before use, each ampoule of the drug is carefully and carefully inspected for damage, color changes, and integrity.

• Scarification method of administration. Immediately before use, the contents of the ampoule must be resuspended in a solution of aqueous glycerin. 0.5 ml of solvent is injected into an ampoule with 10 cutaneous doses, and 1.0 ml with 20 doses. To form a homogeneous suspension, the ampoule is shaken several times. The graft is injected into the outer surface of the middle third of the shoulder. The grafting site is treated with alcohol. Using a tuberculin syringe with a short needle, one drop of the vaccine is applied to 2 places of future incisions at a distance of 3-4 cm. The skin is stretched and with a sterile smallpox vaccination pen, 2 incisions are made through each drop of the vaccine. Using the flat side of the pen, rub the vaccine into the notches for 30 seconds and allow to dry.
• Subcutaneous method. Before vaccination, the drug is resuspended in 1.0 ml of sterile 0.9% sodium chloride solution. The contents from the ampoule are transferred into a sterile vial with 0.9% sodium chloride. If the ampoule contains 200 subcutaneous doses, then the suspension is transferred to a bottle with 99 ml, and if there are 100 doses, then to 49 ml of solvent. If the vaccine is administered by syringe method, the drug is injected into the area of ​​the lower corner of the scapula. If the vaccine is administered using a needle-free method, the suspension is injected into the external area using an injector with a protector. The injection site is lubricated with 5% iodine tincture.

A reaction to the administration of the drug occurs rarely. If symptoms appear, they quickly (within a few days) disappear without a trace.

Contraindications for administering the vaccine

As with any vaccine, there is a range of contraindications, these include:

• Acute period of infectious and non-infectious infectious diseases. In this case, vaccination is carried out no earlier than a month after the onset of recovery.
• A history of primary or secondary immunodeficiencies.
• Recurrent skin diseases.
• Treatment with glucocorticosteroids, blood products, radiotherapy.
• Diseases of the endocrine system.
• Pregnancy and lactation.

To identify contraindications, the doctor collects complaints and examines patients on the day of vaccination. Thermometry is also carried out.

Side effect

After vaccination, signs of weakness, headache, and hyperthermia may occur on the first day ( heat body) up to 38.5° C. Vaccinations against anthrax in rare cases may be accompanied by local manifestations. Such allergic reactions directly depend on the personal characteristics of the body.

• A day or two after skin scarification, manifestations in the form of redness (hyperemia) or infiltration are possible in the place where the vaccine was administered. Subsequently, yellowish crusts appear in the incision zone.
• Also, within the same period, when carrying out subcutaneous vaccination, manifestations in the form of mild pain, redness or rarely infiltration (less than 5 centimeters) in the manipulation area.

The reactions are not persistent and often go away on their own in a short time.

Doctor's advice. Such manifestations are not a reason to worry, but it is always important to consult a specialist to clarify the condition

Application of the vaccine

Anthrax vaccine is used only for epidemic indications, adhering to certain conditions. The manipulation is carried out in the first half of the year as planned. During the spring-autumn period, conditions are most favorable for infection. The vaccine is used strictly after reaching the age of fourteen. For adolescents and adults, both dry and combined vaccines can be used. Both create specific immunity over the next year. Immunization with the vaccine is strictly contraindicated for children due to its high activity. Also, this type of vaccination cannot be performed on women during pregnancy and lactation.

Most medical representatives speak positively about immunization against anthrax. This is due to the high percentage of morbidity prevented from this infection. Such vaccination must be carried out strictly according to indications, and it is not on the calendar mandatory vaccinations. It is important to remember that almost everything medications can cause unwanted manifestations. Percent adverse reactions extremely small, but it exists. Therefore, people with increased reactivity of the immune system should be wary and warn their doctor in advance about their health status. In this case, you will need to observe for some time after vaccination to prevent complications. Such reactions are rare.

Important! Adverse reactions from a vaccine are much less important than the benefits of creating lasting immunity

Interaction with other drugs for immunoprophylaxis

For adults, after administration of the anthrax vaccine, an interval of at least 30 days should be maintained before another vaccination. For children, this period of time should be at least two months. The anthrax vaccine has high sensitivity To antimicrobial agents. Therefore, manipulation cannot be carried out during antibiotic therapy. If the patient is being treated with glucocorticosteroids, receives courses radiation therapy or administration of blood products, immunization is not allowed in the first six months.

Vaccine storage conditions

The vaccine is stored in accordance with sanitary and epidemiological rules. In a temperature range from zero to eight degrees, out of the reach of children. Ampoules under vacuum are stored for four years, without vacuum insulation in a vial or ampoule for less - three years. Transportation must also be carried out in accordance with sanitary and epidemiological rules at the established temperature. It is possible to transport the vaccine for no more than twenty days at temperature conditions not exceeding 25 degrees Celsius.

Vaccine analogues

IN Russian Federation Two drugs for immunoprophylaxis have been officially registered.

• Anthrax vaccine live dry. It is used for both scarification and subcutaneous administration. This preparation uses live spores of a special strain for STI vaccines.
• Anthrax vaccine for subcutaneous use is a combined lyophilisate from a complex of live spores of a special strain for immunization STI-1 and highly concentrated PA (anthrax antigen), which has protective effect. PA is adsorbed (placed) on a gel base of aluminum hydroxide.

Both vaccines are immunostimulants and are used to create a specific reaction. Aimed at combating anthrax bacteria.

On pharmaceutical market can be found in addition to domestic drugs foreign analogues. They will vary slightly in price and are not easy to find.

Anthrax dry live vaccine STI—Vaccinum anthraxicum vivum siccum STI.

Characteristics of the drug

The anthrax dry live vaccine STI is a vacuum-dried suspension of spores of the vaccine strain STI-1. To prepare it, a resistant variant (mutant) of anthrax bacilli is used that lacks the ability to cause disease in humans.

The name of the vaccine (STI) is given in honor of the institute where it was developed by N. N. Ginsburg and A. L. Tamarin. The dry, yellowish-white vaccine is suspended in water within a few minutes without the formation of flakes or sediment.

Purpose, indications and contraindications

Live anthrax vaccine STI is intended to create active immunity against anthrax. Children aged 14 to 16 years are vaccinated against anthrax only for epidemic indications and by decision of the Ministry of Health of the Union Republic. Children under 14 years of age are not subject to vaccination. Revaccination is carried out annually with an interval of one year according to indications.

Contraindications for vaccination against anthrax are:

acute infectious diseases or exacerbation of chronic ones;

feverish condition;

diabetes;

heart disease in the stage of decompensation;

diseases accompanied by cachexia;

peptic ulcer of the stomach and duodenum during an exacerbation;

rheumatism during exacerbation;

acute nephritis;

acute liver damage and cirrhosis;

bronchial asthma, severe emphysema;

diseases thyroid gland(II-III degrees);

lymphogranulomatosis;

skin diseases with extensive damage to the skin surface;

malignant neoplasms.

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The causative agent of anthrax belongs to the genus Bacillus, a species
B. anthracis is included in group 18 (Gram-positive rods and endospore-forming cocci) of Bergey's determinant.
B. anthracis - large rods with straight ends, motionless. They form a capsule in the body. Endospores are oval, highly resistant to many adverse effects. No more than one spore is formed per cell. When exposed to a favorable environment, the spores germinate within a few hours and begin the vegetative form. Gram positive. Facultative anaerobes. Biochemically active.
The main antigens of the anthrax pathogen include polysaccharide cell wall antigen, protein capsular antigen, protective antigen and exotoxin antigen.
The main virulence factor of B. anthracis is the capsule. Mutants defective in capsule formation are avirulent and are used as vaccine strains. Another important factor virulence - toxin formation. A multicomponent complex of exo-iendotoxins was found in anthrax bacteria.
Anthrax is a particularly dangerous zoonotic infection. In natural conditions It affects domestic animals, mainly cattle, horses, pigs, in which anthrax can even be asymptomatic. People become infected when caring for sick animals, cutting up the carcasses of forcedly slaughtered sick animals, eating their meat, and dressing the skins of dead animals. Infection is possible through indirect contact through objects infected with the blood or secretions of sick animals, as well as through infected objects.
Infection occurs through the skin, mucous membranes of the gastrointestinal tract or Airways. Depending on this, cutaneous, intestinal or pulmonary forms of anthrax are distinguished. The last two, as a rule, pass into the septic form with high lethality.
After an illness, a fairly strong immunity is developed. It is antimicrobial and antitoxic in nature.
The material for research is determined by the clinical form of the disease. To detect the pathogen, microscopy of smears from pathological material and immunoindication methods are used. Bacteriological research carried out only in high security laboratories. At complex diagnostics Anthrax uses the anthrax allergen - anthraxin.
To treat anthrax, in addition to antibiotics, anti-anthrax serum and specific gamma globulin are used.
Specific prevention is carried out with live anthrax vaccine. A chemical vaccine has also been developed based on the protective antigen. For emergency prevention, anthrax globulin is used.
Anthrax live dry vaccine "STI" for people
To prepare the vaccine, a persistent non-capsular variant (mutant) of anthrax bacilli is used, which is devoid of the ability to cause disease in humans and farm animals. The finished product is a dried suspension of live spores of the vaccine strain.
In order to obtain a vaccine, a spore culture of a vaccine strain grown on a solid nutrient medium is washed off the surface of the agar with distilled water, the required concentration of spores in the resulting suspension is established, it is poured into ampoules, frozen and dried under vacuum conditions. Dried vaccine ampoules are sealed under vacuum. Each ampoule contains 8-10 billion spores of the vaccine strain. The dry vaccine has the appearance of a porous mass of yellowish-white color, which is evenly suspended within 2-3 minutes without the formation of flakes or sediment.
Depending on the indications, anthrax vaccine can be applied cutaneously (scarification) or subcutaneously. In both cases, the vaccine is given once.
For cutaneous vaccination, the dry vaccine is diluted immediately before use, strictly observing the rules of asepsis with a sterile aqueous solution glycerin, a bottle of which is placed in each box of vaccine. The contents of one ampoule, diluted in 1 ml of glycerin solution, is 20 cutaneous vaccination doses. The skin of the outer surface of the middle third of the shoulder is treated with alcohol or ether before grafting. After the alcohol or ether has evaporated, two drops of 0.02-0.03 ml of diluted vaccine are applied to the treated area of ​​skin with a syringe and a thin needle in two places at a distance of 3-4 cm from each other. Through each applied drop, 4 parallel incisions are made with a sterile pen, after which the vaccine is rubbed into the incisions with the flat side of the grafting pen and allowed to dry for 10 minutes.
The result of vaccination with cutaneous administration is recorded after 24-48 hours. The grafting reaction is considered positive if there is pronounced hyperemia and swelling on the skin along the incisions.
For subcutaneous vaccination, the dry vaccine is diluted with a sterile physiological solution of sodium chloride: from a bottle containing 100 ml of physiological solution, take 2-3 ml and transfer the dry vaccine to the wampula. The ampoule is carefully shaken until a homogeneous suspension is formed, which is transferred back to the bottle with physiological solution. Thus, 100 ml of vaccine is obtained, in which the contents of one ampoule are suspended - about 100 million spores per ml. The subcutaneous vaccination dose is 50 million spores in 0.5 ml of suspension.
Diluted vaccines used for both cutaneous and subcutaneous administration are good for 4 hours, after which the remainder of the unused vaccine is destroyed by boiling for 2 hours.
Routine vaccination against anthrax is carried out according to professional indications by the cutaneous method.
Unscheduled vaccination against anthrax for epidemiological reasons is carried out subcutaneously.
Children aged 14 to 16 years are vaccinated only for epidemiological reasons and only by the skin method. Children under 14 years of age are not subject to vaccination.
Dried live vaccine should be stored in a dark, dry place at a temperature not exceeding 8 °C. Storage and transportation of the vaccine at temperatures below 0 °C are allowed.
The shelf life of the vaccine is 3 years. The expiration date is indicated on each ampoule. After 3 years, the unused vaccine can be subjected to re-control by the institute that released the drug. Provided that the quality of the vaccine meets the established requirements, first of all, if a sufficient number of live spores of the vaccine strain are preserved in the preparation, the shelf life of the tested series can be extended for another 2 years.
Dry live aerosol anthrax vaccine
The drug is a porous grayish-white mass, which is converted into a vapor-dispersed state using a special device - a sprayer.
The active principle of the vaccine is live spores of an avirulent highly immune strain of anthrax bacilli, which has typical signs. 1 gram of dry mass must contain at least 30 billion spores, of which 90% are alive. The drug is controlled for specific harmlessness and immunity.
Aerosol immunization is carried out twice at an interval of 1 month.
The shelf life of the vaccine is 1 year.
Anti-anthrax globulin
For passive prevention and treatment of anthrax in humans, anti-anthrax globulin is used, the active principle of which is β- and γ-globulin fractions obtained by alcohol precipitation from horse anti-anthrax hyperimmune serum.
In addition to the usual controls used in the manufacture of serum preparations, anti-anthrax globulin is tested for specific activity. When administered intravenously at a dose of 1 ml/kg to six rabbits, it should protect at least four of them from infection with a virulent culture of anthrax bacilli.
For prophylactic purposes, it is administered intramuscularly - for adults in a dose of 20-25 ml, for adolescents - 12 ml, for children - 5-8 ml.
For therapeutic purposes, it should be administered as early as possible, in the same way, in an amount of 30-35 ml and, if necessary, again.
The shelf life of globulin is 2 years.
Anthraxin
Anthraxin is a diagnostic drug and is intended for the detection of skin-allergic sensitization tests in patients with anthrax who have recovered from or been vaccinated against this infection.
Anthraxin is a colorless transparent liquid obtained by hydrolysis of anthrax bacilli grown on a nutrient medium. Active beginning The drug is a protein-polysaccharide-nucleic acid complex, extracted by hydrolysis from bacilli. Anthraxin is packaged in 1 ml vampules. This amount corresponds to 10 skin diagnostic doses.
The reaction is administered on the inner surface of the forearm strictly intradermally at a dose of 0.1 ml. The result is taken into account after 24-48 hours.
In people infected with the anthrax microbe or immunized with anthrax vaccine, as a result of immunoallergic restructuring of the body, following the administration of anthraxin, hyperemia and infiltration occur within 6-10 hours, reaching their maximum development one day after administration of the drug.
The shelf life of the drug is 1 year.
Luminescent adsorbed anthrax antibodies
To detect anthrax bacilli in pure and mixed cultures, in samples from various environmental objects and in material from sick people and animals, luminescent anthrax antibodies can be used.
The raw materials for their preparation are adsorbed anti-anthrax serums. The drug has strict specificity; it does not glow to heterologous bacteria, ibacillus, which allows it to be regarded as a valuable means of indicating the causative agent of anthrax.