For passive immunization against hepatitis B is used. Passive immunization

14.07.2020

Passive immunization - the introduction of antibodies to any antigens. With the help of passive immunization, you can create only temporary immunity lasting 1-6 weeks. Although passive immunization causes a short-term increase in resistance to the pathogen, its effect is immediate. Repeated passive immunization does not enhance immunity and is often accompanied by complications. Passive immunization is used to create temporary immunity after contact with an infectious agent in cases where active immunization for one reason or another is not carried out in advance (for example, against cytomegalovirus, against rabies). Passive immunization is also used to treat diseases caused by bacterial toxins (in particular, diphtheria), snake bites, spider bites and for specific (anti-Rh0 (D) -immunoglobulin) and nonspecific (anti-lymphocytic immunoglobulin) immunosuppression.

Three types of drugs are used for passive immunization: - normal human immunoglobulins (outdated name - gamma globulin) for intramuscular or intravenous administration; - specific human immunoglobulins with a high content of antibodies against certain pathogens (for example, against hepatitis B virus or against varicella-zoster virus); - specific sera, including antitoxic ones, obtained from immunized animals.

By origin, there are homologous (made from human blood serum) and heterologous (from the blood of hyperimmunized animals) drugs. The first drugs are administered at once in full dose, the second - according to the Bezredki method. First, 0.1 ml of 1: 100 diluted normal horse serum is injected intradermally and the reaction is monitored for 20 minutes. The test is considered positive if the papule diameter reaches 1 cm or more. In case of a negative result of the intradermal test, the administration of sera begins with a subcutaneous injection of 0.1 ml, and if there are no reactions within 30 minutes, then the rest of the serum is injected intramuscularly. With a positive intradermal test, serum is injected only for unconditional indications, that is, with a threat to the patient's life. In this case, a subcutaneously diluted serum is first injected, which is used for making an intradermal test at 20-minute intervals at doses of 0.5, 2.0 and 5.0 ml, which leads to desensitization. If there is no reaction to these doses, then 0.1 ml of undiluted hyperimmune serum is injected subcutaneously, then after 30 minutes - the entire prescribed dose. In case of a reaction to one of the doses of the therapeutic serum, it is administered over anesthesia, having a syringe with adrenaline or ephedrine at the ready. According to the direction of action, drugs are divided into antitoxic, antiviral and antibacterial.

Antiviral Homologous immunoglobulins anti-rabies anti-rotavirus against hepatitis B anti-influenza anti-tick-borne encephalitis against cytomegalovirus Heterologous immunoglobulins anti-rabies against Venezuelan equine encephalomyelitis against tick-borne encephalitis against Ecephalic fever against Japanese fever

Antibacterial Homologous immunoglobulins complex immunoglobulin preparation (CIP). KIP is a lyophilized protein solution containing immunoglobulins of the IgG, IgA, IgM classes, isolated from human blood plasma. Heterologous immunoglobulins lactoglobulin coliprotein antileptospirosis anthrax

Immune sera Immune sera are preparations from animal and human blood containing antibodies against pathogens of infectious diseases or their metabolic products. In the process of cooking I.S. The blood serum of animals or people (donors) immunized with certain antigens or those who have been ill is subjected to different, depending on the type and purpose of IS, treatment: purification, in which ballast substances are removed and active, primarily globulin, protein fractions are released. The administration of immune serum from the blood of animals to humans may be accompanied by complications (serum sickness, anaphylactic shock). Concentrated immune sera - gamma globulins from human blood - practically do not cause these complications and are removed from the body more slowly. Depending on the purpose, therapeutic and prophylactic and diagnostic immune sera are distinguished. Therapeutic and prophylactic immune sera are subdivided into antitoxic - against poisonous products of the vital activity of microbes (for example, anti-tetanus, anti-diphtheria, anti-gangrenous) and against the effects of the bite of poisonous snakes and insects; antibacterial - affecting the microorganism (anti-anthrax gamma globulin) and antiviral (for example, measles, antirabies, influenza gamma globulins).

Immunoglobulins This type of immune preparation contains ready-made antibodies. They are used for therapeutic, prophylactic purposes, as well as for emergency prevention of infectious diseases. Immunoglobulins can have antimicrobial, antiviral, or antitoxic effects. Immunoglobulin is obtained from placentas or donated blood. The latter is more refined and does not contain hormonal substances. The positive aspects of using immunoglobulins - a ready-made set of antibodies is injected into the body in a sufficient dose within a short period of time. At the same time, the drug is rapidly destroyed, suppresses the synthesis of its own immunoglobulin, and allergizes the body.

Normal human immunoglobulin (measles) is prepared from the blood serum of donors, as well as placental and abortion blood. It contains antibodies against the measles virus in a sufficiently high concentration, antibodies against the causative agents of influenza, chickenpox, polio, rubella, whooping cough, diphtheria and many other bacterial and viral infections in various concentrations, because it is prepared from a mixture of a large number of adult sera, which during their life they could have suffered various diseases or underwent various types of vaccinations.

Immunoglobulins of targeted action are prepared from the blood of people specially immunized against specific infectious diseases, as well as by sampling the blood of those donors in whom an increased content of antibodies to a certain pathogen is determined without prior immunization.

Anti-tetanus immunoglobulin Human anti-tetanus immunoglobulin is a concentrated solution of a purified fraction of immunoglobulins isolated by fractionation with ethyl alcohol from the blood plasma of donors immunized with tetanus toxoid. The active principle of the drug is class G immunoglobulins, which have the activity of antibodies that neutralize tetanus toxin. The maximum concentration of antibodies in the blood is reached within hours after administration; the half-life of antibodies from the body is 3-4 weeks.

Antistaphylococcal plasma Received at blood transfusion stations from donors immunized with staphylococcal toxoid. After the immunization and the appearance of specific antibodies in the blood in a titer of 6.0-10 IU / L, the donors undergo plasmapheresis. During plasmapheresis, a portion of blood is extracted from the body, which is then divided into plasma and corpuscles, blood cells are returned to the body, and the removed plasma is used.

Neutralization of the source of infection is achieved by timely identification of all patients and virus carriers with the subsequent organization of their treatment and monitoring, completely excluding the possibility of spreading the disease in the environment of patients.

Hepatitis B vaccination regimens

To create strong immunity, a threefold reduction of the vaccine is necessary. The first two injections can be considered initial doses, while the third serves to enhance antibody production. The schedule of administration can vary significantly, with the second injection usually being given 1 month after the first, and the third one 3 or 6 months after the second. In some cases, you can resort to an accelerated vaccination regimen, for example, according to the scheme of 0-1-2 months or 0-2-4 months. At the same time, an earlier formation of a protective level of antibodies in a larger number of patients is noted. When using regimens with a longer interval between the second and third injections (for example, 0-1-6 or 0-1-12 months), seroconversion occurs in the same number of patients, but the antibody titer is higher than with the appointment of accelerated vaccination regimens. The vaccine dose is calculated by age, taking into account the drug used.

In many countries, vaccination against hepatitis B is included in the immunization schedule and begins immediately after birth and is carried out on a schedule of 0-1-6 months. In some countries, vaccination is carried only in at-risk groups (medical professionals, primarily surgeons, dentists, obstetricians, blood transfusion service workers, patients on hemodialysis or often receiving blood products, etc.). Children born to mothers who are carriers of the hepatitis B virus are subject to compulsory vaccination. In these cases, it is recommended immediately after birth (no later than 48 hours) to inject 0.5 ml of immunoglobulin against hepatitis B virus (optional in recent years) and start three-fold immunization with the scheme 0-1-6 months

The hepatitis B vaccine is administered only intramuscularly, in adults and older children it should be injected into the deltoid muscle, in young children and newborns, it is preferable to inject into the anterolateral part of the thigh. Injections of the vaccine into the gluteal region are undesirable due to a decrease in the strength of the immune system.

Currently, according to the national calendar, newborns from risk groups are vaccinated according to the scheme of 0-1-2-12 months of age.

Children who do not belong to risk groups are vaccinated against hepatitis B according to the 0-3-6 scheme (the first dose is at the start of vaccination, the second is 3 months after the first vaccination, the third is 6 months after the start of immunization).

Post-vaccination immunity

According to our clinic, in newborns vaccinated in the first 24 hours of life with the recombinant Endzherix B vaccine according to the 0-1-2 month schedule with revaccination at 12 months, seroconversion occurred in 95.6% of cases, while the level of anti-HBs after the third dose amounted to 1650 + 395 IU / L. and before revaccination - 354 + 142 IU / l. After the introduction of the revaccinating dose, the level of antibodies increased 10 times or more. One month after the end of the Endzherix B vaccination course in different groups (newborns, medical workers, students, etc.), a protective antibody titer is detected in 92.3-92.7% of the vaccinated. After 1 year, antibody titers decrease, but remain protective in 79.1-90% of the vaccinated.

The vaccination efficiency index ranged from 7.8 to 18.1, but in patients with hemodiatization units it was only 2.4.

Based on the generalized experience of using the Endzherix B vaccine in 40 countries of the world, WHO concluded that the seroconversion rate after the introduction of 3 doses according to the scheme 0-1-2 or 0-1-6 months approaches 100% Introduction of the third dose in the 2nd month, compared with the introduction of the third dose at the 6th month, ultimately leads to a less significant increase in antibody titers, therefore, the 0-1-6 month immunization scheme can be recommended for routine vaccination, while the 0-1-2 months - in cases where you need to quickly achieve a sufficient degree of immunity. In the future, in these children, a more reliable level of antibodies can be achieved by administering a booster dose after 12 months.

It is more difficult to resolve the issue of the duration of post-vaccination immunity. According to most of the literature sources, the level of antibodies after the completed three-time vaccination decreases rapidly during the first 12 months after vaccination, then the decrease in the level occurs more slowly. Most authors are inclined to believe that, most likely, there is no need to revacinate patients with high seroconversion rates (above 100 IU / d). At the same time, it is suggested that the body's immunological memory is as reliable a means of protection against HBV infection as regular administration of maintenance doses of the vaccine. The UK Ministry of Health believes that until the question of the duration of post-vaccination immunity is finally clarified, it should be considered appropriate to revaccinate patients with a protection level below 100 IU / L.

Vaccination reactions and complications after hepatitis B vaccination

Recombinant hepatitis B vaccines are low reactive. Only a few patients have a reaction at the injection site (mild hyperemia, less often edema) or a general reaction in the form of a short-term increase in body temperature to 37.5-38.5 ° C.

In response to the introduction of foreign recombinant vaccines (Endzherix B, etc.), local reactions (soreness, hypersensitivity, itching, erythema, ecchymosis, swelling, nodule formation) occur in a total of 16.7% of those vaccinated; among general reactions, asthenia was noted in 4.2%, malaise - in 1.2, fever - in 3.2, nausea - in 1.8, diarrhea - in 1.1, headache - in 4.1%; also possible increased sweating, chills, hypotension, Quincke's edema, decreased appetite, arthralgia, myalgia, etc.

Similar adverse reactions are described for the introduction of the domestic vaccine kombiotech. All these reactions do not significantly affect the health state, are short-lived and, most likely, are caused by the presence of yeast protein impurities in recombinant vaccines.

Precautions and contraindications for hepatitis B vaccination

There are no permanent contraindications to vaccination against hepatitis B, However, in people with hypersensitivity to any component of the vaccine (for example, baker's yeast protein), as well as in the presence of a severe infectious disease, vaccination should be postponed or canceled.

With some caution, vaccination against hepatitis B should be carried out in patients with severe cardiovascular insufficiency, patients with chronic diseases of the kidneys, liver, central nervous system. However, such conditions do not serve as a contraindication to the administration of recombinant vaccines, and given that these patients are especially often infected with hepatitis B during various parenteral manipulations during examination and treatment, it becomes obvious that they should be vaccinated first.

One has to take into account the fact that in patients with immunodeficiency conditions (malignant neoplasms, hemoblastosis, congenital and acquired immunodeficiencies, etc.) and in patients on immunosuppressive therapy, an increase in the frequency of vaccine administration is required to create intense immunity (Scheme 0-1-3 -6-12 months).

Vaccination in pregnant women can be carried out only if the potential benefit justifies the possible risk to the fetus.

About combining hepatitis B vaccination with the introduction of other vaccines

The implementation of the Russian Hepatitis B Vaccine Prevention Program, starting from the neonatal period, invariably raises the question of combining the vaccine with other vaccines, and primarily with the BCG vaccine, before each pediatrician. From a scientific point of view, the fear of the incompatibility of these vaccines is groundless, since it is known that an increase in the level of protection with the introduction of the BCG vaccine is achieved due to the formation of cellular immunity similar to post-vaccination allergy, whereas with the introduction of the hepatitis B vaccine, humoral immunity is formed.

Studies show that with the introduction of the recombinant yeast vaccine Engerix B in the first 24-48 hours of life and vaccination on the 4th-7th day against tuberculosis, no side effects are observed. At the same time, 95.6% of children developed protective immunity against hepatitis B and did not there was a noticeable decrease in the level of protection against tuberculosis, which could be judged by the stable level of incidence of tuberculosis after the start of mass vaccination against hepatitis B

On the other hand, the introduction of the hepatitis B vaccine immediately after the birth of a child is justified only in cases where there is a high risk of infection of the child during childbirth or immediately after birth, that is, in children born to mothers who are carriers of the hepatitis B virus or patients with hepatitis B, as well as in regions with a high prevalence of HB viral infection. First of all, these are the regions of Siberia, the Far East, the Republic of Tyva, Kalmykia, etc.

Of course, it can theoretically be assumed that if a pregnant woman does not have hepatitis B markers (HBsAg, anti-HBcopy), then vaccination in newborns can be delayed to later periods of life. But with such an approach, it is impossible to give guarantees that infection will not occur in the postnatal period: the fermentation house, in the neonatal pathology department, etc. That is why in regions with a high level of HBsAg carriage, it is undoubtedly necessary to start vaccination immediately after birth and regardless of whether or not markers of hepatitis B are found in the mother.

Children from families where there is a carrier of HBsAg or a patient with hepatitis B are also subject to priority vaccination against hepatitis B. According to studies, in families where there is a source of infection, markers of HBV infection are found in 90% of mothers, 78.4% of fathers and 78, 3% of children. A similar pattern can be traced in children's homes and boarding schools, that is, in institutions where there is close contact and there is a high probability of transmission of infection by the so-called contact route, through microtrauma, household items, etc. It is better to start vaccination of gray-negative children in such foci after a mass examination children for markers of hepatitis B. If for some reason it is impossible to determine the markers of hepatitis B, vaccination can be carried out without waiting for the test results. At the same time, one should not exaggerate the negative consequences of the vaccine administration to children (and adults) who have post-infectious immunity or even active infection. The introduction of an additional dose of immunizing antigen in the form of a recombinant vaccine should be regarded as a positive rather than a negative factor, since it is known that an additional dose of the immunizing antigen has a booster effect, and there are practically no side reactions.

For this reason, attempts are being made to treat chronic hepatitis B or HBsAg carriage by administering a vaccine against hepatitis B. According to American pediatricians, the determination of markers of hepatitis B may be more expensive than vaccination itself, since only a positive effect should be expected from the introduction of a vaccine, it is more rational to vaccinate without prior expensive laboratory research.

The order of the Ministry of Health "On the introduction of prophylactic vaccinations against hepatitis B" provides for mandatory vaccination of patients who regularly receive blood and blood products, as well as those on hemodialysis. Vaccination in these cases should be carried out four times according to the scheme of 0-1-2-6 months, while in patients on hemodialysis, the vaccine vines are doubled.

Vaccination of children against hepatitis B with oncohematological diseases

As you know, patients with hematological malignancies, solid tumors and hemophilia are especially often infected with the hepatitis B virus during treatment.

According to research data, with a single screening examination, markers of hepatitis B are found in 60.2% of patients with hemoblastosis, in 36.5 - with solid tumors, in 85.2 - with hemophilia, and only in 6% of patients with acute intestinal infection, and in children from families at home - in 4.3% of cases. It would seem that patients with hemoblastosis, solid tumors and hemophilia should be vaccinated in the first place, but it is known that in conditions of immunodeficiency, the development of immunity to the administration of the vaccine is significantly slowed down or the protective level of antibodies is not formed at all. Our data confirm the low level of protection in response to the hepatitis B vaccine in patients with hematological malignancies, but, given the too high risk of infection and the consequences of infection with the hepatitis B virus, it is recommended to vaccinate against hepatitis B as soon as the diagnosis of cancer is made. Vaccination in such patients should be carried out before the appearance of protective immunity according to the scheme: 0-1-3-6-12 or 0-1-2-3-6-12 months.

Introduction ………………………………………………………………………… 3
1. Passive immunization ……………………………………………… .... 4
2. Immunoglobulins ………………………………………………………… .5
3. Gammaglobulins …………………………………………………………… .7
4. Preparations intended for passive immunization …………… .9
Conclusion …………………………………………………………………… 14
Literature …………………………………………………………………… ..15

Introduction
Active immunization, or vaccination, is the administration of a vaccine or toxoid to form a long-term defense of the body. Live vaccines are usually contraindicated in patients receiving immunosuppressants due to fever or during pregnancy
Passive immunization provides temporary immunity in the body by introducing foreign immune substances such as antibodies.
Active immunization acts prophylactically - after a certain time and for a long period (after vaccination with Tetanus Toxoid (AS) - 2 years, after the 1st revaccination of the AS - up to 5 years, after several revaccinations of the AS - up to 10 years).
Passive immune drugs (immunoglobulin, serum) act immediately, but are quickly destroyed, which does not allow their use for long-term protection from infections. But it is an excellent tool for the emergency prevention of rabies (with bites), tetanus (with injuries), influenza, measles, mumps, tick-borne encephalitis and a number of other infections, as well as the treatment of staphylococcal infection and Ebola fever.
Vaccination against infectious diseases is one of the most powerful and effective methods of clinical medicine. Thanks to immunization, many previously widespread infections, such as smallpox, poliomyelitis, measles. Have been eliminated or substantially limited. However, complacency and socioeconomic boundaries make it difficult to deliver immunization that meets the needs of humankind. Adults, in particular, usually do not receive immunizations against pneumococcal and tetanus-diphtheria infections.

1. Passive immunization
Passive immunization - the introduction of antibodies to any antigens. With the help of passive immunization, you can create only temporary immunity lasting 1-6 weeks. Although passive immunization causes a short-term increase in resistance to the pathogen, its effect is immediate. Repeated passive immunization does not enhance immunity and is often accompanied by complications. It is usually carried out after contact with the pathogen and when active immunization is impossible.
Passive immunization is used to create temporary immunity after contact with an infectious agent in cases where active immunization for one reason or another is not carried out in advance (for example, against cytomegalovirus, against rabies).
Passive immunization is also used to treat diseases caused by bacterial toxins (in particular, diphtheria), poisonous snake bites, spider bites and for specific (anti-Rh0 (D) -immunoglobulin) and nonspecific (antilymphocytic immunoglobulin) immunosuppression.
Three types of drugs are used for passive immunization:
- normal human immunoglobulins (outdated name - gammaglobulin) for intramuscular or intravenous administration;
- specific human immunoglobulins with a high content of antibodies against certain pathogens (for example, against the hepatitis B virus);
- specific sera, including antitoxic ones, obtained from immunized animals.

2. Immunoglobulins
This type of immune preparation contains ready-made antibodies. They are used for therapeutic, prophylactic purposes, as well as for emergency prevention of infectious diseases.
Immunoglobulins can have antimicrobial, antiviral, or antitoxic effects.
Immunoglobulin is obtained from placentas or donated blood. The latter is more refined and does not contain hormonal substances. Finally, it is possible to obtain a single venous immunoglobulin.
The positive aspects of using immunoglobulins - a ready-made set of antibodies is injected into the body in a sufficient dose within a short period of time. At the same time, the drug breaks down relatively quickly, inhibits the synthesis of its own immunoglobulin, and allergizes the body. In addition to the allergenic effect of the immunoglobulin itself, nonspecific immunoglobulins with heterogeneous allotypes, isotypes and antibodies to them, allergic substances and impurities - blood group factors, isoantibodies, hormones, enzymes, amino acids, etc. are not indifferent to the body. The latter, during long-term storage, expose and form the active center of the immunoglobulin. fragments that additionally sensitize the body.
Healing sera were the prototype of modern immunoglobulin drugs, and some of them (antidiphtheria and anti-tetanus) have not lost their clinical significance to this day. However, the development of technology for processing blood products made it possible to implement the ideas of passive immunization, first in the form of concentrated immunoglobulin preparations for intramuscular administration, and then in the form of immunoglobulins for intravenous administration.
For a long time, the effectiveness of immunoglobulin drugs was explained solely due to the passive transfer of antibodies. By binding to the corresponding antigens, antibodies neutralize them, convert them into an insoluble form, as a result of which the mechanisms of phagocytosis, complement-dependent lysis and subsequent elimination of antigens from the body are triggered.
However, in recent years, due to the proven effectiveness of intravenous immunoglobulins in some autoimmune diseases, the actual immunomodulatory role of immunoglobulins has been actively studied. Thus, intravenous immunoglobulins were found to have the ability to alter the production of interleukins and the expression level of receptors for IL-2. The effect of immunoglobulin preparations on the activity of various subpopulations of T-lymphocytes and a stimulating effect on the processes of phagocytosis was also demonstrated.
Intramuscular immunoglobulins, used since the 1950s, have relatively low bioavailability. Resorption of the drug is carried out from the injection site within 2-3 days and more than half of the drug is destroyed by proteolytic enzymes.
The duration of the created immunity depends on the concentration of antibodies in the preparation and their stability; on average, the half-life of passively administered homologous antibodies is 35-40 days. Repeated administrations of immunoglobulin are allowed only in extremely unfavorable situations: due to the production of anti-immunoglobulin antibodies, the effectiveness of fractional passive immunization is much lower than that of a single-stage one.
In the tactics of immunoglobulin prophylaxis, two types of actions are distinguished:
1) the introduction of immunoglobulin before probable contact with the pathogen, for example, when an immunized person leaves for an area endemic for this infection;
2) the introduction of immunoglobulin after probable contact with the pathogen, possibly even during the incubation stage, for example, in a children's institution after the detection of a case (s) of an infectious disease and isolation of its source.
For obvious reasons, the effectiveness of prevention in the first situation will be higher than in the second, all other things being equal. In case of hepatitis B, prophylactic administration of a specific immunoglobulin with a high content of antibodies to the surface antigen of the virus, anti-HBs is recommended to be given to newborns whose mothers have had this disease during pregnancy or are chronic carriers of the HBs antigen, since in these cases the probability of infection of the child is very high. Specific anti-HBs immunoglobulin is also used to prevent illness in hospital staff, blood transfusion stations and scientific laboratories after traumatic injury to the skin or mucous membranes, which occurred when working with human blood.
3. Gammaglobulins
Globulin is a member of a group of simple proteins that dissolves well in dilute saline solutions and coagulates when exposed to heat. Various globulins (serum globulins) are present in the blood, including alpha, beta, and gammaglobulins. Some globulins have important functions as antibodies; others are responsible for the transport of lipids, iron and copper in the bloodstream. Almost all gammaglobulins are immunoglobulins.
Immuno- (gamma) globulin prophylaxis has been widely used as a means of combating hepatitis A. Injection of gammaglobulin provides a person with temporary protection against hepatitis A; in addition, it has recently been found that these injections reduce the likelihood of coronary artery injury from Kawasaki disease.
Information about its effectiveness is contradictory, which is evidently explained by the variety of epidemic situations and the non-standardness of the drugs used with respect to the content of antibodies. Were recommended massive injections of immunoglobulin in the period preceding the expected rise in incidence (so-called pre-seasonal prophylaxis) and small-scale vaccinations in children's groups in which cases of jaundice were recorded (so-called prophylaxis according to indications). Currently, the indications for the use of immunoglobulin for the prevention of hepatitis A are sharply limited. Under all circumstances, the prevention of hepatitis A with immunoglobulin did not affect the epidemic process, i.e. the spread of infection in this area, although it prevented the development of icteric forms in timely vaccinated persons.
In the beginning, heterogeneous serum preparations and immunoglobulins obtained from immunized animals were used. At the second stage, homogeneous sera were obtained, i.e. sera from an immunized person. When using serum, a lot of ballast substances are introduced into the recipient's body, therefore, it is more rational to use immunoglobulin (gammaglobulin), which is one of the fractions of the total blood protein.
Specific antibodies used for therapeutic purposes are produced by the industry in the form of immune sera or immune-active fractions - immunoglobulins.
They are prepared from the blood of humans (homologous) or animals (heterologous). Homologous immune drugs have a definite advantage over heterologous ones due to the relatively long duration (up to 1-2 months) of their circulation in the body and the absence of side effects.
Serums and immunoglobulins made from animal blood act for a relatively short time (1-2 weeks) and can cause adverse reactions. They can be used only after checking the sensitivity of the patient's body using an intradermal test with diluted drugs.
Serum is prescribed with a negative test, to prevent complications, it is administered by Bezreko, after preliminary desensitization of the body, carried out by sequential subcutaneous (with an interval of 30-60 minutes) introduction of small portions of this substance. Then the entire dose of the therapeutic serum is applied intramuscularly. In certain forms of exotoxic infections (toxic pharyngeal diphtheria), 1 / 2-1 / 3 of the drug during its first administration can be administered intravenously.

4. Preparations intended for passive immunization
In Russia, intramuscular immunoglobulins containing increased titers of antibodies to antigens of certain pathogens are produced: tick-borne encephalitis virus, influenza, herpes and cytomegalovirus, HBS - antigen (Antihep).
Intravenous immunoglobulins have significant advantages because their use makes it possible to create effective concentrations of antibodies in the blood in the shortest possible time.
Intravenous immunoglobulins are used for primary immunodeficiencies (agammaglobulinemia, selective IgG deficiency, etc.), hypogammaglobulinemia in chronic lymphocytic leukemia, thrombocytopenic purpura, other autoimmune diseases, as well as in severe viral and bacterial infections, for the prevention of infectious diseases, sepsis complications.
Complex immunoglobulin preparation (CIP). The KIP contains human immunoglobulins of three classes: Ig A (15-25%), Ig M (15-25%) and Ig G (50-70%). From all other immunoglobulin preparations, KIP is distinguished by a high content of Ig A and Ig M, an increased concentration of antibodies to gram-negative enteropathogenic bacteria of the intestinal group (Shigella, Salmonella, Escherichia, etc.), a high concentration of antibodies to rotaviruses, as well as oral administration. Instrumentation is used for acute intestinal infections, dysbacteriosis, chronic enterocolitis, allergic dermatoses, combined with intestinal dysfunction.
Close to immunoglobulin drugs in terms of passive transfer of immunity is the drug Affinoleukin. It contains a complex of low molecular weight proteins of human leukocyte extract, capable of transferring immunoreactivity to antigens of common infectious diseases (herpes, staphylococcus, streptococcus, mycobacterium tuberculosis, etc.) and affinity binding to them. The introduction of Afinoleukin leads to the induction of immunity against those antigens for which the donors of leukocytes had immunological memory. The drug has undergone clinical trials in the treatment of herpes simplex, herpes zoster, hepatitis, adenovirus infections, in addition to the main therapy, which did not give the expected results.
Diphtheria. For the treatment of patients with diphtheria in our country, anti-diphtheria serum purified and concentrated by the "Diaperm-3" method is produced.
In a number of European countries and the United States, human anti-diphtheria gamma globulin is also produced for these purposes. Serum is obtained from the blood of horses hyperimmunized with diphtheria toxoid. Its dose and method of administration are determined by the clinical form of the disease.
Botulism. The main drug for immunotherapy of patients with botulism is anti-botulinum horse purified and concentrated serum of types A, B, C, Her F. , prepared from the blood of donors immunized with botuloanatoxins of types A, B and E. The 1st ampoule contains one therapeutic dose of the drug. Anti-botulinum serum is produced in the form of monovalent sets (one ampoule of each type of serum is in the package) or polyvalent (one ampoule contains 3, 4 or 5 types of antitoxins). The ampoule with monovalent serum contains one therapeutic dose of antitoxic bodies of the corresponding type (for type A - 10,000 ME, type B - 5,000 ME, type C - 10,000 ME, type E - 10,000 ME, type F - 300 ME). Each ampoule with multivalent serum contains the same amount of antibodies against all five or three types of botulinum toxin (antitoxins of types C and F, due to the limited need for them, are usually not included in the kit).
Treatment of patients with botulism, when the type of toxin causing the disease is unknown, begins with the use of a polyvalent drug or a mixture of monovalent sera. They are administered intravenously. In case of difficulties in intravenous administration of serum, it is prescribed intramuscularly. Usually 1 - 1.5 therapeutic doses of the drug are administered. In a severe course of the disease, serum is used repeatedly (1-4 times) with an interval of 6-8 hours at a 1.5 times greater dose than in a moderate form of the disease. Re-introduction is carried out intramuscularly.
If the type of causative agent of botulism is established in the early stages of the disease, patients are treated with monovalent serum.
The duration of the course of serotherapy is determined by the clinical form of the disease and the dynamics of the disappearance of neurological, cardiovascular and other disorders. With a mild form of the pathological process, it usually does not exceed 2 days, and with a severe one - 4-5 days.
Tetanus. For the treatment of patients with tetanus, anti-tetanus purified and concentrated horse serum, as well as human anti-tetanus gamma globulin, are indicated.
Serum is obtained from the blood of horses immunized with tetanus toxoid. It is used for patients with tetanus intramuscularly at 100-200 thousand IU (depending on the severity of the patient's condition). Simultaneously, 5-10 thousand IU of the drug is injected into the tissues surrounding the wound.
When the patient's body is allergic to a foreign protein, it is advisable to use a specific gamma globulin prepared from the blood of donors immunized with tetanus toxoid instead of serum.
The drug is prescribed for therapeutic purposes once in a dose of 6-12 ml intramuscularly.
Staphylococcal infection. With staphylococcal infection (staphylococcal sepsis, staphylococcal pneumonia, etc.), the main effective treatment for patients is drugs containing specific antibodies - anti-staphylococcal immunoglobulin, anti-staphylococcal plasma, as well as heterogeneous immunoglobulin produced in some neighboring countries (Georgia).
Anti-staphylococcal immunoglobulin is prepared from the blood of donors immunized with staphylococcal toxoid. The drug is produced in ampoules of 3-5 ml, which contain 100 IU of specific antibodies. A single (aka daily) dose of anti-staphylococcal immunoglobulin in acute staphylococcal sepsis should be 10 IU / kg of body weight (therefore, for a patient weighing 70 kg, it is equal to the amount of the drug contained in 7 ampoules). The course of treatment for staphylococcal sepsis should last 8-10 days, with staphylococcal pneumonia 3-5 days, with staphylococcal osteomyelitis 5-8 days or more.
Due to the viscous consistency of anti-staphylococcal immunoglobulin, it should be collected and injected using a thick needle.
Anti-staphylococcal plasma is the liquid part of the blood of people immunized with staphylococcal toxoid. The antitoxin (antibodies) contained in it has a pronounced therapeutic effect in diseases of staphylococcal etiology - sepsis, pneumonia, osteomyelitis, peritonitis, as well as in localized purulent processes.
1 ml of plasma contains at least 6 IU of antitoxin.
Anti-staphylococcal plasma is produced frozen (in sterile plastic bags with a capacity of 10 to 250 ml) and dried (in sealed glass vials with a volume of 250 ml, 125 ml of the drug - for intravenous administration and in 10 ml vials of 2 ml of the drug - for local application). Frozen plasma is thawed before use in water heated to 37.0 ° C. The flakes that appear during this soon dissolve, and the plasma becomes transparent. The appearance of a thin layer of white sediment at the bottom of the bag with plasma is not a contraindication for its use. A prerequisite in this case is the use of a system for transfusing medicinal solutions with a filter.
Plasma turbidity, the presence of a coarse sediment, flakes, films in it are evidence of its infection and unsuitability for medicinal use.
Dissolve dry plasma before use with distilled water. After that, it should not contain flakes, clots, sediment. Anti-staphylococcal plasma is usually given intravenously. In case of acute staphylococcal sepsis, it is prescribed 200 ml once every 2 days. With severe course
An anti-staphylococcal heterogeneous immunoglobulin is obtained from the blood of horses immunized with staphylococcal toxoid. 1 ml of the preparation contains 800 IU of antitoxin. In acute staphylococcal sepsis, 1–2 ml / day of immunoglobulin is prescribed. However, it has a very high reactogenicity and in 1/5 of cases it gives side reactions (mainly serum sickness).
Polio. Mumps. To prevent the complicated course of these diseases in the early stages of the manifestation of the infectious process, normal human immunoglobulin (20 ml intramuscularly) is used.
The drug is made from placental, aborted venous blood of people

Conclusion
Currently, the microbiological industry in Russia and other countries produces immune sera and immunoglobulins for the treatment of patients with various infectious diseases. This is provided for the causative agents of those diseases in the pathogenesis of which exotoxins play of paramount importance (diphtheria, botulism, tetanus, etc.), as well as a number of diseases dangerous to human health - staphylococcal infection, anthrax, leptospirosis, influenza, rabies, tick-borne encephalitis.
The effectiveness of immune sera (immunoglobulins) is largely determined by their optimal dose and timeliness of use. The dose of the drug must correspond to the clinical form of the infectious process and be able to neutralize not only the antigens of pathogens that are circulating in the body at a given moment, but also those that may appear in it in the interval between drug injections.
The antimicrobial and clinical effect of immune sera (immunoglobulins) is higher the earlier they are used. Their appointment after the 4-5th day of illness rarely gives a pronounced positive result.
Gammaglobulins from human blood are areactogenic. Only in individuals who are extremely sensitive can they cause a short-term increase in body temperature.
Sometimes there is a reaction to repeated administration of these drugs: an itchy urticarial rash develops 1-3 days after using the serum.

Literature

1. Topical issues of epidemiology and infectious diseases. Semina N.A. Semina. - M .: Medicine, 1999 - 147s.
2. Lisitsyn Yu.P., Polunina N.V. Public health and health care: Textbook. M .: 2002 - 216 p.
3. Obukhovets T.P. Fundamentals of Nursing. Workshop. Series "Medicine for You" - Rostov n / a: "Phoenix", 2002 - 410 p.
4. Guidelines for prevention in practical health care. Ed. Glazunova I.S., Oganova R.G. and others - M .: 2000 .-- 217 p.
5. Tatochenko V. K., Ozeretskovsky N. A., Immunoprophylaxis: (reference book. - 6th ed., Add.). M., 2003 - 174s.

CHAPTER 19. VACCINES AGAINST HEPATITIS AND IMMUNOPROPHYLAXIS

1. What can you say about the development of the concept of immunization (vaccination)?

Over the past century, thanks to remarkable discoveries in the field of microbiology, significant progress has been made in the treatment and prevention of infectious diseases. In 1798, Edward Jenner first published information on the use of smallpox vaccine. He found that people who were vaccinated and infected with the vaccinia virus became immune to smallpox. E. Jenner called this procedure vaccination. This was the first time a vaccine was used to prevent the development of a disease. The word "vaccine" comes from the Latin word for "cow", because it was the cows that were the "hosts" of the virus used to make the first real vaccine.
The success of immunization is based on one main idea: a person has specific immunological mechanisms that can be programmed to protect the body from pathogens of infectious diseases. Stimulation of immune mechanisms is carried out through the direct administration of infectious agents or parts thereof in the form of a vaccine. The golden era of vaccination began in 1949 with the discovery of viral reproduction in cell culture. The first patented product made with the new technology was the trivalent formalin-inactivated poliomyelitis vaccine Salk. Soon, vaccines against viral hepatitis A and B were created (the causative agents of which were discovered in 1973 and 1965, respectively).

2. What are the differences between active and passive immunizations?

Active immunization is based on the introduction of a specific antigen into the body, which stimulates the production of antibodies that prevent the development of the disease. Passive immunization, or immunization, is the administration of ready-made antibodies to prevent the development or change in the natural course of the disease in suspected infected individuals. Antibodies are obtained as a result of immunization of animals and humans, and are also taken from the serum of those who have recovered naturally.

3. List the main types of vaccines.

The classic method for producing vaccines is to modify the infectious agent so that the final product is suitable for human use. Currently, 2 types of vaccines are widely used: (1) inactivated (or killed) vaccines that contain a pathogen that cannot multiply in the host's body, but retains antigenic properties and the ability to stimulate the production of antibodies; (2) live, attenuated vaccines made from viable but weakened microorganisms that cannot cause a detailed picture of the disease. The end result of vaccination is the production of antibodies and prevention of disease development. Live vaccines usually contain relatively low concentrations of infectious agents. They, as a rule, are administered once, which provides long-term stable immunity. The immune response when vaccinated with killed vaccines corresponds to the concentration of the antigen. To create long-term immunity, revaccination is often required.

Human vaccines


LIVE	KILLED	VACCINES CONTAINING PURIFIED PROTEINS (OR POLYSACCHARIDES)
Smallpox (1798)	Antirabies	Containing diphtheria
Antirabic (1885)	(recently received)	toxoid (1888)
Against yellow fever (1 935)	Typhoid	Diphtheria (1923)
Poliomyelitis (Sabin)	Against Cholera (1896)	Tetanus (1927)
Measles	Anti-plague (1897)	Pneumococcal
Against mumps	Influenza (1936)	Meningococcal
Against rubella	Poliomyelitis (Salk)	Against Hemophilus influenzae
Adenoviral	Against hepatitis A (1995)	Against hepatitis B (1981)
Against hepatitis A (under investigation)

4. What is immunization?

In immunoprophylaxis, or passive immunization, ready-made antibodies obtained as a result of immunization of animals and humans or from the serum of naturally ill patients are used to prevent the development or change the natural course of the disease in an infected person. Passive immunization provides only short-term protection of the body (from several weeks to several months). Immunoprophylaxis was considered the main method of preventing the development of viral hepatitis A and B before the advent of appropriate vaccines. Passive immunization can also be carried out naturally during the transfer of class G immunoglobulins from the mother to the fetus. Thus, the blood of a newborn contains a certain amount of maternal antibodies, which for several months provide protection against many bacterial and viral infections, that is, they protect the child from infection in that critical period when his immune system is not yet fully formed. During the first year of life, maternal antibodies disappear.
At the dawn of the development of passive immunization, serum containing antibodies (for example, horse serum) was injected directly into the recipient's blood. Recently, a method has been developed for fractionation of serum, followed by the isolation and concentration of the required antibodies.

Immunoglobulins suitable for human use


A DRUG	A SOURCE	APPLICATION
Serum immunoglobulin		Prevents the development of measles Prevents the development of hepatitis A
Measles immunoglobulin	Mixed human plasma	Prevents the development of measles
Hepatitis B immunoglobulin	Mixed donor plasma with high antibody titer	Used when there is a risk of infection by direct parenteral route (needle stick) or sexually
Rabies immunoglobulin	Mixed plasma from hyperimmunized donors	Used in complex immunotherapy of rabies
Anti-botulinum antitoxin	Specific equine antibodies	Treatment and prevention of botulism

5. What viruses cause acute and chronic hepatitis?


ACUTE HEPATITIS	CHRONIC HEPATITIS	MAIN TRANSMISSION PATH
Hepatitis A virus (HAV)	No	Fecal-oral
Hepatitis B virus (HBV)	Yes	Parenteral
Hepatitis C virus (HCV)	Yes	Parenteral
Hepatitis D virus (HDV)	Yes	Parenteral
Hepatitis E Virus (HEV)	No	Fecal-oral

6. What type of immunization is used for hepatitis A?

Serum immunoglobulin G (IgG) is a very good preventive measure. If the time of possible contact with the pathogen (for example, stay in places of increased risk of infection) does not exceed 3 months, IgG is administered at a dose of 0.02 ml / kg. In case of longer contact, it is recommended to repeat the administration of the drug every 5 months at a dose of 0.06 ml / kg. Immunoprophylaxis with immunoglobulin G gives excellent results. However, this method is very impractical, since immunity is created only for several months. IgG is generally safe, but fever, myalgia, and pain at the injection site may occur.

7. Is there a vaccine against hepatitis A?

There are several vaccines for hepatitis A, but only two inactivated vaccines have shown satisfactory clinical results. The first study, led by Werzberger et al., Demonstrated 100% efficacy of an inactivated vaccine given once to individuals at increased risk for hepatitis A. The study involved 1,037 children aged 2-16 years living in upstate New York, where the annual incidence of acute hepatitis A is 3%. Children were blindly recruited and injected intramuscularly with either highly purified formalized hepatitis A vaccine (Merck, Sharp & Dohme, West Point, PA) or placebo. Between 50 and 103 days after injection, 25 cases of hepatitis A were noted in the placebo group. In the group of children who received the vaccine, not a single child fell ill (p< 0,001). Таким образом, вакцина обеспечила 100 % невосприимчивость к гепатиту А. В другом исследовании, выполненном Иннис (Innis) и соавт., изучалась эффективность инактивированной вакцины (Havrix, SmitnKline, Rixensart, Belgium), отличной от той, которую использовал Верзбергер. В исследовании принимали участие более 40 000 детей из Таиланда. Сравнение эффективности вакцины с плацебо показало, что 3-кратная вакцинация (введение трех доз) предотвращает развитие гепатита А в 97 % случаев. Недавно вакцина была одобрена Food and Drug Administration (США) для назначения определенным группам населения (военным, туристам). Ее вводят внутримышечно (в дельтовидную мышцу); рекомендуемая доза - 1440 ЕД (1,0 мл); ревакцинацию проводят через 6 месяцев или 1 год.

8. What is the difference between inactivated hepatitis A vaccine and live attenuated vaccine?

Hepatitis A vaccines

	INACTIVATED (KILLED)	ATTENUATED (LIVE)
Source of receipt Method of receipt	Cultivation of HAV in vitroFormalin inactivation	Cultivation of HAV / n vitroMultiple passages through cell culture
Immunogenicity	Contains aluminum as an adjuvant; stimulates the production of antibodies against hepatitis A virus	An adjuvant is not needed; stimulates the production of antibodies against hepatitis A virus
disadvantages	Multiple revaccinations required	Can theoretically become virulent again and cause acute hepatitis A
Availability	Industrial production in the USA and Europe	Research continues in the USA, Asia and Europe

9. What method of immunoprophylaxis is used for hepatitis B?

There are two ways to prevent hepatitis B:
1. Active immunization.Before and after contact with the pathogen, it is recommended to use the hepatitis B vaccine, first patented in the USA in 1981.
2. Passive immunization.Hyperimmune globulin provides temporary passive immunity and is administered to some patients after contact with the pathogen.

Hyperimmune globulin contains high concentrations of anti-HBs. This is its main difference from conventional immunoglobulin, which is obtained from plasma with different concentrations of anti-HBs. In the United States, the titer of HBs antibodies in hyperimmune globulin exceeds 1: 100,000 (according to the results of radioimmunoassay).

Immunization against hepatitis B after infection

HYPERIMMUNE GLOBULIN			VACCINE
INFECTION	DOSE	TIME	DOSE	TIME
In the perinatal period	0.5 ml intramuscularly	Within 12 hours after birth	0.5 ml at birth	Within 12 hours after birth; revaccination after 1 and 6 months
During sexual intercourse	0.6 ml / kg intramuscularly	Single injection within 14 days after sexual intercourse	The vaccine is administered simultaneously with hyperimmune globulin	Immunization should be started immediately

11. How many hepatitis B vaccines are there in the United States? What is the difference between them?

Three vaccines are patented in the USA for practical use. They are comparable in immunogenicity and efficacy, but differ in their preparation method.
1. Heptavax-B (Merck, Sharp & Dohme) was developed in 1986. It contains the surface antigen of the hepatitis B virus isolated from the plasma of patients with chronic hepatitis. The vaccine stimulates the production of antibodies to the determinant andHBs antigen, effectively neutralizing various subtypes of hepatitis B virus. Its effectiveness has been confirmed by numerous facts, but its production is very expensive, and purification and inactivation requires the use of various physical and chemical methods. Taking into account these difficulties, alternative methods of obtaining a vaccine have been developed, the leading of which is the method of recombinant DNA. 1 ml of plasma-derived vaccine contains 20 μg HBsAg.
2. Recombivax-HB was obtained in 1989 and is manufactured by Merck, Sharp & Dohme Research Laboratories (West Point, PA). It is a non-infectious, non-glycosylated vaccine containing HBsAg adw subtype, produced using recombinant DNA technology. Yeast cells (Saccharomyces cerevisiae),which is fixed with HBsAg, cultured, centrifuged and homogenized using glass beads, after which HBsAg is purified and absorbed on aluminum hydroxide. 1 ml of vaccine contains 10 μg HBsAg.
3. Engerix-B (SmithKline Biologicals, Rixensart, Belgium) is a non-infectious recombinant hepatitis B vaccine. It contains the surface antigen of the hepatitis B virus, which is fixed on genetically engineered yeast cells. The cells are cultured, after which HBsAg is purified and absorbed on aluminum hydroxide. 1 ml of vaccine contains 20 μg HBsAg.

12. How are adults and children immunized with the hepatitis B virus vaccine?

Recombivax-HB vaccine (Merck, Sharp & Dohme)

GROUP		INITIAL DOSE	IN 1 MONTH	AFTER 6 MONTHS
Small children	Children's dose:	0.5 ml	0.5 ml	0.5 ml
(up to 10 years old)	0.5 ml
Adults and children	Adult dose:	1.0ml	1.0 ml	1.0 ml
older age	10 μg / 1.0 ml
The duration of the existence of antibodies is directly related to their maximum concentration obtained after the third dose of the vaccine. Observation of adult patients vaccinated with Heptavax-B showed that in 30-50% of recipients, antibodies completely disappeared or their level decreased significantly. In the course of long-term studies, it was revealed that, despite the absence of anti-HBs in the blood serum, immunity to the hepatitis B virus in adults and children persists for at least 9 years. Some studies emphasize the fact that over 9 years of observation, the decrease in the level of anti-HBs in the groups of homosexuals and Eskimos of Alaska (the groups most at risk of contracting hepatitis B) was 13-60%. Nevertheless, although the revaccination was not carried out, all immunized persons remained 100% immune to the disease. Individuals who had completely lost anti-HBs had "serological" outbreaks of infection in subsequent years (the diagnosis was made when HBs antibodies were detected in the serum). At the same time, there were no clinical symptoms and HBsAg was not determined, from which it follows that such manifestations have no clinical significance, and after vaccination, persistent immunity is formed. Thus, revaccinating healthy adults and children is not recommended. Patients with immunosuppressive conditions (for example, those on hemodialysis) need to receive an additional dose of the vaccine when the level of anti-HBs decreases to 10 IU / ml or below. 14. Is the vaccine always effective? The main epitope of HBsAg is the determinant and,the production of antibodies to which is stimulated by vaccines against hepatitis B. It is believed that the determinant a forms a spatial bond between amino acids 124 and 147. Although it is stable, there are sometimes variants that are unable to neutralize anti-HBs. Mutations of the hepatitis B virus have been reported, which are likely to occur accidentally and are not restored due to a deficiency of an internal enzyme, polymerase. Significant differences have been reported between hepatitis B vaccines (originally in Italy, but also in Japan and Gambia). According to Italian researchers, 40 out of 1600 immunized children developed symptoms of the disease, despite the corresponding production of antibodies in response to the administration of the HBV vaccine. The mutant virus had amino acid changes: 145 in Italy, 126 in Japan, and 141 in Gambia. Whether the mutant virus alters the clinical course of hepatitis remains unknown, since no large-scale epidemiological studies have been conducted to study the incidence, prevalence and clinical correlation. 15. Can the introduction of hepatitis B vaccine be harmful to virus carriers? No adverse effects were observed in 16 chronic HBsAg carriers following vaccine administration. Vaccination was carried out with the aim of eliminating the carrier. However, this goal was not achieved: none of the subjects showed the disappearance of HBsAg from the serum or the production of antibodies. This fact makes it possible to narrow down the indications for vaccination against hepatitis B. 16. Is Hepatitis C Immunoprophylaxis Reasonable? There are no firm recommendations for preventing the development of hepatitis C after exposure to the pathogen. Research results on this issue remain dubious. Some scientists in the case of percutaneous infection recommend prescribing immunoglobulin at a dose of 0.06 mg / kg. Moreover, prevention should be started as early as possible. However, experiments on chimpanzees have shown insufficient effectiveness of passive immunization against hepatitis C virus infection. Moreover, the results of recent studies indicate that neutralizing antibodies produced in humans during an infectious disease are present in serum for only a short time and do not protect against reinfection. Thus, immunoprophylaxis of hepatitis C is a rather difficult task. It is very difficult to develop an adequate vaccine due to the presence of numerous viral genotypes, to which it is not possible to create cross-protection. 17. Is it possible to simultaneously immunize people against hepatitis A and B? In at least two studies, seronegative volunteers were administered simultaneously vaccines against hepatitis A and B (injections were carried out in different parts of the body), after which the results of antibody production in these patients were compared with those in other studies who received only one vaccine (or against hepatitis A, or against hepatitis B). No undesirable effects were observed. In contrast, one study found higher levels of antibodies to the hepatitis A virus in volunteers. Now that the hepatitis A vaccine has become widely available, this early experience suggests that people can be given both vaccines at the same time without fear of developing serious side effects.

Foreword ……………………………………………………………………… 1

Hepatitis A virus ………………………………………………………………… 2

Transmission method ……………………………………………… 2

Disease …………………………………………………… 2

Clinical course .................................. ... ............. ..… ........ 3

Treatment...........…………………....................……......... ........... 3

Complications...............................……................ ......................... 3

Prevention ...............................................…. …....................4

Passive immunization ............................... ... ................ .........five

Active immunization ............................. ……… ................ ....five

Vaccines against hepatitis A .................................. ...…… ......... ........................... 6

Vaccine "GEP-A-in-VAC" ........................................ ......………..........................8

Production and composition ........................................... …… .. ................................…ten

The effect of the drug ........................................... ... ... ... ...........ten

The period of maintaining immunity ....................... ... .................. 10

Combination with passive immunization .................................. 11

Dosage...........................................…….... ..........................eleven

Indications and use of the drug "GEP-A-in-VAK" ........ …… ................... 11

Contraindications ................................. ... ... .............. ............12

Side effects ...................................... ……… ....... ..........12

Et al. - "Comparative study of the immunogenicity of the inactivated vaccine against hepatitis A" Ge-A-in-Vak "according to experimental and clinical studies" "Vopr. Virology", 5, 268-270.

, - "Optimization of the conditions for obtaining an inactivated vaccine against hepatitis A and its characteristics" "Vopr. Virology", 6, 215-218, 1995.

And others - "Assessment of reactogenicity and immunogenicity of the cultured concentrated inactivated vaccine against hepatitis A" Hep-A-in-Vac "," Vopr. Virology "5, 219-220, 1995.

And others - "Study of the domestic cultural concentrated inactivated vaccine against hepatitis A" Hep-A-in-Vac "," Journal of Microbiology ", 1, 50-54, 1998.

, - "On the development of requirements and quality control methods for the first inactivated vaccine against hepatitis A." in the book "Modern features of the development of the epidemiological process in a large city" - Mat-ly nauch. practical. Conf., pp. 38-40.-M. 1995.

A.I., A- "Results of field tests of the domestic vaccine against hepatitis A" Hep-A-in-Vak ", - Materials of scientific practical conf., Pp. 211-212.-M. 1997.

G, - "Characteristics of reactogenic and immunogenic properties of the children's version of domestic vaccines against hepatitis A" Vopr. Virology ", 3, 133-138, 1999.

, - "Development of the cultured concentrated purified inactivated vaccine against hepatitis A" Hep-A-in-Vac "- Buluten" Vaccination "No. 4 (16), July-August 2001

CONTRAINDICATIONS

Acute infectious and non-infectious diseases, exacerbations of chronic diseases. In these cases, the vaccination is carried out no earlier than 1 month. after recovery (remission).

Immunodeficiency states, malignant blood diseases and neoplasms.

Strong reaction (temperature above 400C; hyperemia, edema at the injection site with a diameter of more than 8 cm) to the previous vaccination "Hep-A-in-Vac".

In order to identify contraindications, the doctor (paramedic) examines and interviews the vaccinated person with mandatory thermometry on the day of vaccination. If necessary, an appropriate laboratory examination is carried out.

SIDE EFFECTS

The drug "GEP-A-in-VAK" does not cause significant side effects. Side effects associated with the use of the drug do not exceed similar indications when using other vaccines containing purified antigens adsorbed by aluminum. Of the local side effects, painful sensations in the area of \u200b\u200bthe injection, a slight increase in temperature and slight malaise are most often noted. Redness, hardening and swelling of the injection site is sometimes observed. Local adverse reactions are observed from 4 to 7% of the total number of vaccinated and disappear after 1-2 days.

ADMINISTRATION OF VACCINE TO PREGNANT WOMEN

AND NURSING MOTHERS

The effect of the drug on fetal development has not been specifically studied, however, as is the case with all inactivated viral vaccines, the possibility of a negative effect of this vaccine on fetal development is considered negligible. During pregnancy, the drug should be used only if clearly necessary.

DISEASE

The target organ for hepatitis A virus is the liver, and the primary cells of the lesion are hepatocytes. After ingestion, viral particles are absorbed through the mucous membrane of the gastrointestinal tract and enter the general blood circulation system.

Once in the liver, the virus is recognized by receptor sites on the hepatocyte membrane and absorbed by the cells. Virus decapsidation occurs inside the cell, viral RNA is released and transcription begins. Viral proteins are synthesized and assembled into new capsids, each containing newly replicated viral RNA strands. The HA virion is packed into vesicles and secreted from the cell into the bile ducts that pass between the hepatocytes. The vesicle membrane dissolves in bile, HAV particles are released, followed by their entry into feces or infection of neighboring hepatocytes.

CLINICAL CURRENT

The typical clinical course of hepatitis A has four stages:

1 Incubation period;

2 Prodromal phase;

3. Icteric phase;

4 Convalescence.

The severity of the disease usually depends on the age of the patient. In young children, it is usually asymptomatic or causes atypical symptoms, often without jaundice. In adults, a clinically significant infection develops, often with jaundice, which is generally more severe in patients aged 40 and above.

Disease course and mortality

The average duration of the disease is 27-40 days, and 90% of patients are hospitalized. Within six months after the illness, there is a recovery period, during which it is necessary to comply with a medical and protective regime, a special diet and a doctor's supervision.

Hepatitis A is fatal in a very small number of cases, most of which occur in transient hepatitis A.

Higher mortality is observed among people with chronic liver disease who develop acute hepatitis A.

TREATMENT

There are no specific effective treatments for hepatitis A, which is self-limiting, so prevention is the preferred medical intervention.

DOSAGE

Each dose is a sterile 1.0 ml suspension for adults and 0.5 ml for children. The vaccine should be given as supplied. Strictly observe the recommended doses. The standard course of vaccination of the drug consists of two doses, given 6-12 months apart between the first and second vaccinations. The vaccine "GEP-A-in-VAK" is intended only for intramuscular injection into the deltoid muscle.

INDICATIONS AND APPLICATION OF THE PREPARATION
"GEP-A-in-VAK"

Hepatitis A vaccine “GEP-A-in-VAK” is intended for active vaccination against hepatitis A.

In regions with a low and moderate prevalence of hepatitis A, vaccination with GEP-A-in-VAC is especially recommended for people who are or will be at increased risk of infection, including the following categories of people:

People traveling to regions with a high prevalence of hepatitis A on business or leisure travel (Africa, Asia, the Mediterranean, the Middle East, Central and South America, Kazakhstan, Turkmenistan, Uzbekistan) usually have a high risk for tourists in these regions due to the following factors :

greens and fruits washed in contaminated water;

uncooked food prepared by an infected person;

swimming in contaminated water;

Military personnel traveling or serving in regions with an increased prevalence of hepatitis A and with a low level of sanitation and hygiene are at increased risk of contracting hepatitis A. They are shown active vaccination;

People who can become infected with hepatitis A in connection with their professional activities and who are at risk of becoming carriers of the virus: kindergarten workers, workers in children's homes and homes for the disabled, nurses who care for patients, medical and

service personnel of hospitals and other medical institutions, especially gastroenterological and pediatric departments, locksmiths

Currently, the treatment of patients with hepatitis A is supportive in nature and is aimed at ensuring a comfortable state of the patient and maintaining an adequate balance of nutrients and electrolytes. Most doctors allow patients to eat whatever they like (although fatty foods are nauseous for most patients), provided that the diet contains enough fluids, calories, and protein.

PREVENTION

Given the lack of specific treatments, usually late, epidemically ineffective hospitalization, as well as the possibility of prolonged treatment and the adverse consequences of hepatitis A, its prevention should be considered the most effective means of combating this infection, which is currently most radically provided by vaccination. The possibility of specific prevention of hepatitis A is one of the most important achievements of biology and medicine in recent years. Nonspecific prevention of hepatitis A, as a classic cellular infection, rests on the solution of socio-economic, sanitary-hygienic and environmental problems of society and is difficult to achieve.

Routine immunoprophylaxis with the introduction of normal immunoglobulin has a short-term, for 2-3 months, protective effect. in addition, antibodies to hepatitis A in normal immunoglobulin are now often contained in a low titer. Because of this, passive immunoprophylaxis, which for many years was the only measure of struggle, today does not solve either regional or global problems. Only vaccine prophylaxis can fundamentally solve these problems.

PASSIVE IMMUNIZATION

In the 1940s, researchers found that immunoglobulins obtained from convalescent hepatitis A patients who developed natural immunity contained specific antibodies against the hepatitis A virus. Currently, immunoglobulins are produced by large-scale separation and concentration of serum proteins from donor plasma ... Immunoglobulin is effective only in 85% of cases. The duration of the protective effect during passive immunization is no more than 3-5 months. Currently, passive immunization is used only in some cases for urgent travel to areas endemic for hepatitis A (together with the vaccine) and in children in case of close contact with a patient in a family or childcare facility.

safety, sterility and immunogenicity. The production process consists of several main stages:

Development of a producer culture.

Infection of the producer culture.

Collection of virus from cell culture.

Purification and concentration.

Complete inactivation of the virus with formaldehyde.

Getting the finished form.

Inactivation is several times higher than the minimum required period of inactivation of hepatitis A virus. Purified and inactivated hepatitis A virus, after passing all controls, is adsorbed on aluminum hydroxide. The vaccine "GEP-A-in-VAK" is a suspension of inactivated, purified virions of the hepatitis A virus (HAV), adsorbed on aluminum hydroxide, there are no preservatives.

EFFECT OF THE PREPARATION

The hepatitis A vaccine creates immunity to infection with the hepatitis A virus, promoting the formation of specific antibodies in the body that act against this virus.

The vaccine stimulates the production of antibodies to the hepatitis A virus in no less than 98% of seronegative individuals on days 21-28 after a full course of immunization. The vaccine can be used both for mass immunization and for individual protection against hepatitis A.

PERIOD OF PRESERVATION OF IMMUNITY

The vaccination course consists of two intramuscular injections of vaccines with an interval of 6-12 months between the first and second vaccinations. By creating a stable active immunity in the vaccinated, the duration of the preservation of immunity is at least 12-15 years. For groups of people in need of long-term protection, vaccination is a more practical way to obtain it than the administration of immunoglobulin.

COMBINATION WITH PASSIVE IMMUNIZATION

Active and passive immunization can be used simultaneously to provide both immediate and long-term protection to humans, with an immediate protective effect usually achieved. With the parallel use of the vaccine and immunoglobulin, the drugs should be injected into different parts of the body.

Since 1997, the industrial production of the first domestic vaccine "GEP-A-in-VAK" for the needs of public health began.

Since 1997, the first domestic vaccine has been approved by the MIBP committee as a means of active prevention of viral hepatitis A in children from 3 years of age, adolescents and adults. In 1999, GISK them. repeated tests of the vaccine "GEP-A-in-VAK" for reactogenicity, harmlessness and immunogenicity in the adult contingent were carried out. The results once again confirmed the findings of the 1992, 1997 State Vaccine Trials. The study of the immunogenic activity showed that one month after the first test of the GEP-A-in-VAK vaccine, the seroconversion rate was 75%, while the geometric mean titer (SD) of anti-HAV corresponded to 106.7 mIU / ml, which corresponds to the protective titer antibodies when using the ELISA test system "Vector". One month after the second vaccination, the immunogenicity index was 96.2% of seroconversions with anti-SHT, 4 mIU / ml. Currently, according to the NTD approved in 2001 (FSP, RP No. 000-01 and instructions for use), the hepatitis A vaccine "GEP-A-in-VAK" is used to prevent hepatitis A in children from the age of three, adolescents and adults. The full course of vaccination consists of two vaccinations carried out with an interval of 6-12 months and provides long-term protection against viral hepatitis A. The vaccine provides active immunity against hepatitis A by stimulating the body's production of antibodies against hepatitis A. Considering the relationship between the level of antibodies and the duration of immunity, you can count on the creation of stable immunity lasting at least 10-15 years, after a full course of vaccination (two vaccinations). A single administration of the vaccine (1 dose) protects the body for 1-2 years one month after the administration of the drug.

PRODUCTION AND COMPOSITION

For the production of the vaccine "GEP-A-in-VAK" use the strain LBA-86, obtained in IPVE them. RAMS as a result of the adaptation of the HAS-15 strain to the 4647 cell line approved for vaccine production, which meets all the requirements of the World Health Organization. The hepatitis A virus grows very slowly, and it takes about three weeks to reach the harvest stage of the virus grown in cell culture.

Vaccine production is not only time consuming but also complex. A number of known and new physicochemical and molecular biological tests, as well as controls on animals and in cell culture, are provided at all stages of vaccine production, from the production strain to the finished vaccine. This system reliably ensures that the final product meets the standards requirements

ACTIVE IMMUNIZATION

It is known that vaccine prophylaxis is one of the main ways in the system of epidemiological measures in the fight against infection. Therefore, in recent years, active research has been carried out in many countries of the world to develop vaccines against hepatitis A.

Hepatitis A vaccines are administered subcutaneously or intramuscularly. It showed that a single injection of the vaccine protects against infection, however, for a longer preservation of immunity, its repeated administration is necessary. As a rule, adults and children are vaccinated twice with an interval of 6-18 months. The introduction of the vaccine leads to the appearance of protective antibodies to the hepatitis A virus 15-28 days after vaccination. The resulting protective immunity lasts for a year after the first vaccination. With the introduction of the second dose of the vaccine 6-12 months after the primary immunization, it is possible to prolong the immunity to hepatitis A up to 15 years. Mass vaccination against hepatitis A is carried out in Israel, several US states, and some provinces in Spain and Italy. In 1999, the US government called on all states to include hepatitis A vaccination on their immunization schedules. The use of the vaccine provides long-term protection.

VACCINES AGAINST HEPATITIS A

In Russia, vaccines are allowed, which are killed viruses grown in cell culture. To date, the following vaccines are registered in Russia:

Vaccine against hepatitis A cultural purified concentrated adsorbed inactivated liquid "Hep-A-in-Vac" JSC "Vector-BiAlgam" Russia;

Vaccine against hepatitis A cultural purified concentrated adsorbed inactivated liquid with polyoxidonium "Hep-A-in-Vac-Pol" JSC "Vector-BiAlgam" Russia;

Avaxim, Aventis Pasteur, France;

"Vakta" 50 units, "Merck, Sharp and Dome", USA;

"Vakta" 25 Unit, "Merck, Sharp and Dome", USA;

Hawrix 1440, GlaxoSmithKline, England;

Hawrix 720, GlaxoSmithKline, England;

All of these vaccines are based on inactivated hepatitis A antigen adsorbed on aluminum hydroxide.

VACCINE "GEP-A-in-VAC"

In our country, research on the development of approaches to the creation of hepatitis A vaccine prophylaxis began in the 80s of the 20th century. At the Institute of Poliomyelitis and Viral Encephalitis of the Academy of Medical Sciences of the USSR in the laboratory headed by the professor, a scientific basis for such work was created. The methods of cultivating the hepatitis A virus in laboratory conditions have been mastered. The HAS-15 strain of the hepatitis A virus adapted to growth in a 4647 cell culture permitted for vaccine production was selected as the initial strain for obtaining an inactivated vaccine.A stable productive system HAV-cell was developed, a technological scheme for preparing a vaccine, and the first laboratory batch the inactivated vaccine against hepatitis A. After their successful laboratory certification and the first clinical and laboratory tests, the development in its laboratory version was transferred to the State Research Center VB "Vector" (Novosibirsk), where the development of the technology for the production of an industrial-scale vaccine against hepatitis A began, complying with the WHO requirements, in order to introduce it into the practice of Russian medicine.

Vaccine production is a complex and time-consuming process. At all stages of vaccine preparation, starting from the production strain and ending with the finished form of the vaccine, a number of modern physicochemical and molecular biological tests, as well as tests on animals and in cell culture, are provided. This system reliably ensures the safety of the vaccine, a high level of its immunological activity. The finished form of the Hep-A-in-Vac vaccine is a suspension of inactivated purified HAV virions adsorbed on aluminum hydroxide, preservatives and antibiotics are absent in the vaccine.

In accordance with the existing regulation on the procedure for registration of vaccines, according to the test program approved by the Academic Council of the GISK named after and the MIBP Committee, were carried out in 1992 by State trials of the vaccine on volunteers.

At the first stage, studies were conducted in a controlled experience among organized adult contingents. Individuals who did not have HA, who had not received a human immunoglobulin preparation for 6 months before vaccination, and who had no contraindications provided for in the instructions for use, were immunized. The results of reactogenicity and safety of laboratory series and experimental series of the Hep-A-in-Vak vaccine under the conditions of clinical and laboratory observations did not reveal any deviations from the physiological norm in the vaccinated in terms of the cellular composition of peripheral blood, feces, urine, and the level of aminotransferases. The specific safety of the drug was also evidenced by statistically insignificant differences in the incidence of somatic infectious diseases in the experimental and control groups. Moderate reactogenicity of the Hep-A-in-Vac vaccine was manifested by single total

reactions (from 0 to 4%) in the form of an increase in temperature to subfebrile numbers, headache, dizziness. Local reactions were manifested in the form of slight soreness and redness.

When analyzing the results of immunogenic activity, it was found that the full course of immunization with laboratory and experimental series of the Hep-A-in-Vac vaccine provided the formation of anti-HAV antibodies in seronegative volunteers in almost an equal percentage of cases (87.3-94.2%) ...

The study of the prophylactic efficacy of the Hep-A-in-Vac vaccine was carried out among organized contingents of persons aged 18-21 years, totaling 8260 people. Observation of the vaccinated was carried out within 8 months after the end of the course of immunization during the period of the seasonal rise in the incidence of GA. The vaccine efficacy rate was 98%

Thus, trials of the GEP-A-in-VAK vaccine showed almost complete absence of reactogenicity, good tolerability of the drug, specific safety, high immunological activity and 98% prophylactic efficacy of the vaccine. Based on the results of the State Trials of the MIBP Committee, he recommended the introduction of the GEP-A-in-VAK vaccine into public health practice for vaccination of the adult population.

Taking into account the data of State tests in adults, the content of aluminum hydroxide in one inoculation dose was reduced from 1.0 to 0.5 mg, and the stabilizer, human serum albumin, was also excluded.

Taking into account the changes made, in 1995-96, 5 production series were released, which passed the control in the State Institute of Culture and Arts for all the quality parameters required for these drugs. In 1996, a program of State tests of a domestic vaccine for children was developed and approved. In 1997, under the leadership of GISK, he conducted a study of the drug in the children's contingent. The results obtained confirmed the conclusions about the specific safety, moderate reactogenicity and high immunogenic activity of the first domestic vaccine against viral hepatitis A, made at the first stage. After the second stage, permission was obtained from the MIBP committee of the Ministry of Health of Russia to use the Hep-A-in-Vac vaccine in public health practice for mass vaccination of the population from the age of three. Since 1997, the production of a domestic vaccine against hepatitis A has been organized, which is still the only domestic vaccine against this infection.

In subsequent years, highly effective methods for purifying viral antigen were introduced, which made it possible to reduce the content of

cellular DNA from 200 pg / ml to 100 and below pg / ml.

total protein from 125mg / ml to 1mg / ml

These purification methods made it possible to increase the HAV antigen content in one adult dose from 50 ELISA Units to 80 ELISA Units. Since the specific activity of most viral inactivated vaccines, including against hepatitis A, depends on the content of the viral antigen, such an increase made it possible to significantly increase the immunogenicity of the vaccine and switch from three-fold immunization to two-fold.

In 1999, GISK carried out repeated tests of the Hep-A-in-Vac vaccine for reactogenicity, harmlessness and immunogenicity in the adult contingent. the results once again confirmed the conclusions made during the State tests in 1992 and 1997. The study of immunogenic activity showed that one month after the first immunization with the Hep-A-in-Vac vaccine, the seroconversion rate was 75%, while the geometric mean titer (CGTanti-HAV was 106.7 mIU / ml, which corresponds to the protective antibody titer at using the ELISA test system "Vector." One month after the second vaccination, the immunogenicity indicator was 96.2% seroversion with anti-HTGT, 4 mIU / ml, Currently, according to the approved NTD hepatitis A vaccine "Hep-A-in-Vac" used for the prevention of hepatitis A in children from the age of three, adolescents and adults A full course of vaccination consists of two vaccinations, carried out at intervals of 6-12 months after the first vaccination, provides long-term protection against viral hepatitis A. The vaccine provides active immunity against hepatitis And by stimulating the body's production of antibodies against hepatitis A. given the relationship between the level of antibodies and the duration of immunity, we can count on creating the development of persistent immunity lasting at least 15 years, after a full course of vaccination (two vaccinations). A single administration of the vaccine (1 dose) protects the body for 1-2 years one month after the administration of the drug.