What are vaccines and what are they?

For specific prophylaxis. infectious diseases use vaccines that allow the formation of active immunity before their natural contact with the pathogen.

Vaccines intended for the prevention of a single infection are called monovaccines, against two divaccines, against three herbal vaccines, against several polyvaccines. Vaccines containing a mixture of antigens of various microorganisms and toxoids are considered to be associated. Polyvalent vaccines are considered to include several types of serological types of pathogens of a single infection (leptospirosis, colibacteriosis, salmonellosis, pseudomonosis of minks, Marek's disease, etc.).

Vaccines of various types are used for immunoprophylaxis of infectious diseases.

Live vaccines

They are a suspension of vaccine strains of microorganisms (bacteria, viruses, rickettsiae) grown on various nutrient media. Usually for vaccination using strains of microorganisms with reduced virulence or deprived of virulent properties, but fully preserved immunogenic properties. These vaccines are made on the basis of pathogens pathogens, attenuated (weak) in artificial or natural conditions. Attenuated strains of viruses and bacteria are obtained by inactivating a gene responsible for the formation of a virulence factor, or by mutations in genes that nonspecifically reduce this virulence.

In recent years, recombinant DNA technology has been used to produce attenuated strains of some viruses. Large DNA-containing viruses, such as the pox vaccine virus, can serve as vectors for the cloning of foreign genes. Such viruses retain their infectivity, and infected cells begin to secrete proteins encoded by transfected genes.

Due to the genetically fixed loss of pathogenic properties and loss of the ability to cause an infectious disease, vaccine strains retain the ability to multiply at the site of administration, and later on in regional lymph nodes and internal organs. Vaccine infection lasts several weeks, is not accompanied by a pronounced clinical picture of the disease and leads to the formation of immunity to pathogenic strains of microorganisms.

Live attenuated vaccines are obtained from attenuated microorganisms. Weakening of microorganisms is also achieved when growing crops in adverse conditions. Many vaccines with the aim of increasing the time of preservation produce dry.

Live vaccines have significant advantages over those killed, due to the fact that they fully preserve the antigenic set of the pathogen and provide a longer state of immunity. However, given the fact that live microorganisms are the active principle of live vaccines, it is necessary to strictly observe the requirements that ensure the viability of microorganisms and the specific activity of vaccines.

There are no preservatives in live vaccines, when working with them it is necessary to strictly follow the rules of asepsis and antiseptics.

Live vaccines have a long shelf life (1 year or more), they are stored at a temperature of 2-10 C.

5-6 days before the introduction of live vaccines and 15-20 days after vaccination can not be used for the treatment of antibiotics, sulfa, nitrofuranovye drugs and immunoglobulins, as they reduce the intensity and duration of immunity.

Vaccines create active immunity after 7-21 days, which lasts an average of 12 months.

[1], [2], [3], [4], [5],

Killed (inactivated) vaccines

For inactivation of microorganisms used heating, treatment with formalin, acetone, phenol, ultraviolet rays, ultrasound, alcohol. Such vaccines are not dangerous, they are less effective compared to live, but when re-introduction create a sufficiently stable immunity.

In the production of inactivated vaccines, it is necessary to strictly control the process of inactivation and, at the same time, preserve a set of antigens in the killed cultures.

Killed vaccines do not contain live microorganisms. The high efficacy of killed vaccines is associated with the retention of a set of antigens in inactivated cultures of microorganisms that provide an immune response.

For the high efficiency of inactivated vaccines, the selection of production strains is of great importance. For the manufacture of polyvalent vaccines, it is best to use strains of microorganisms with a wide range of antigens, given the immunological relationship of various serological groups and variants of microorganisms.

The spectrum of pathogens used to prepare inactivated vaccines is very diverse, but bacterial (vaccine against necrobacteriosis) and viral (rabies inactivated dry culture vaccine against rabies from Shchelkovo-51 strain) are most common.

Inactivated vaccines should be stored at 2-8 ° C.

[6], [7], [8], [9]

Chemical vaccines

Consist of antigenic complexes of microbial cells connected to adjuvants. Adjuvants are used to enlarge antigenic particles, as well as to increase the immunogenic activity of vaccines. Adjuvants include aluminum hydroxide, alum, organic or mineral oils.

The emulsified or adsorbed antigen becomes more concentrated. When introduced into the body, it is deposited and comes from the site of introduction into the organs and tissues in small doses. Slow resorption of the antigen prolongs the immune effect of the vaccine and significantly reduces its toxic and allergic properties.

The number of chemical vaccines include deposited vaccines against swine erysipelas and porcine streptococcosis (serogroups C and R).

[10], [11], [12], [13], [14]

Associated Vaccines

Consist of a mixture of cultures of microorganisms pathogens of various infectious diseases that do not inhibit the immune properties of each other. After the introduction of such vaccines in the body is formed immunity against several diseases at the same time.

[15], [16], [17], [18], [19], [20], [21], [22],

Anatoxins

These are preparations containing toxins that are devoid of toxic properties, but retain antigenicity. They are used to induce immune reactions aimed at neutralizing toxins.

Anatoxins are produced from exotoxins of various types of microorganisms. For this purpose, toxins are neutralized with formalin and kept in a thermostat at a temperature of 38-40 ° C for several days. Toxoids are essentially analogous to inactivated vaccines. They are cleared of ballast substances, adsorbed and concentrated on aluminum hydroxide. Adsorbents are introduced into toxoid to enhance the adjuvant properties.

Anatoxins create anti-toxic immunity, which persists for a long time.

[23], [24], [25], [26], [27], [28], [29], [30],

Recombinant vaccines

Using the methods of genetic engineering, it is possible to create artificial genetic structures in the form of recombinant (hybrid) DNA molecules. The recombinant DNA molecule with the new genetic information is introduced into the recipient cell by means of genetic information carriers ( viruses, plasmids), which are called vectors.

The preparation of recombinant vaccines involves several steps:

• cloning of genes that provide the synthesis of the necessary antigens;
• introduction of cloned genes into a vector (viruses, plasmids);
• introduction of vectors into producer cells (viruses, bacteria, fungi);
• in vitro cell culture;
• isolation of the antigen and its purification or the use of producer cells as vaccines.

The finished product should be investigated in comparison with a natural reference preparation or one of the first series of a genetically engineered preparation that has passed preclinical and clinical trials.

BG Orlyankin (1998) reports that a new direction has been created in the development of genetic engineering vaccines, based on the introduction of plasmid DNA (vector) with the integrated protective protein gene directly into the body. In it, plasmid DNA does not multiply, does not integrate into chromosomes, and does not cause an antibody formation reaction. Plasmid DNA with the integrated genome of the protective protein induces a complete cellular and humoral immune response.

On the basis of a single plasmid vector, various DNA vaccines can be constructed by changing only the gene encoding the protective protein. DNA vaccines have the safety of inactivated vaccines and the efficacy of live. Currently, more than 20 recombinant vaccines against various human diseases have been designed: vaccine against rabies, Aujeszky's disease, infectious rhinotracheitis, viral diarrhea, respiratory syncytial infection, influenza A, hepatitis B and C, lymphocytic choriomeningitis, T-cell human leukemia, herpes virus infection human and others

DNA vaccines have several advantages over other vaccines.

1. When developing such vaccines, it is possible to quickly obtain a recombinant plasmid carrying the gene encoding the necessary pathogen protein, in contrast to the lengthy and expensive process of obtaining attenuated strains of the pathogen or transgenic animals.
2. Manufacturability and low cost of cultivation of the obtained plasmids in E. Coli cells and its further purification.
3. The protein expressed in the cells of a vaccinated organism has a conformation as close as possible to the native one and has a high antigenic activity, which is not always achieved with the use of subunit vaccines.
4. Elimination of the vector plasmid in the vaccinated organism occurs in a short period of time.
5. With DNA vaccination against especially dangerous infections, the likelihood of the disease as a result of immunization is completely absent.
6. Possible prolonged immunity.

All of the above allows us to call DNA vaccines vaccines XXI.

However, the opinion about the full control of infections with vaccines was kept until the end of the 80s of the 20th century, until the AIDS pandemic shook it.

DNA immunization is also not a universal panacea. Since the second half of XX, infectious agents have become increasingly important, which cannot be controlled by immunoprophylaxis. The persistence of these microorganisms is accompanied by the phenomenon of antibody-dependent intensification of the infection or the integration of the provirus into the genome of the microorganism. Specific prophylaxis can be based on inhibition of pathogen penetration into sensitive cells by blocking recognition receptors on their surface (viral interference, water-soluble compounds that bind receptors) or by inhibiting their intracellular reproduction (oligonucleotide and antisense inhibition of the pathogen genes, killing infected cells with specific cytotoxin and ).

The solution to the problem of integrating a provirus is possible when cloning transgenic animals, for example, when obtaining lines that do not contain a provirus. Therefore, DNA vaccines should be developed for pathogens whose persistence is not accompanied by antibody-dependent enhancement of the infection or preservation of the pro-virus in the host genome.

[31], [32], [33], [34],

Seroprophylaxis and seroterapia

Serum (Serum) form a passive immunity in the body, which lasts for 2-3 weeks, and is used to treat patients or prevent diseases in a threatened area.

Antibodies are contained in immune sera, therefore they are used most often for therapeutic purposes at the onset of the disease in order to achieve the greatest therapeutic effect. Sera can contain antibodies against microorganisms and toxins, so they are divided into antimicrobial and antitoxic.

Get the serum on biofactories and bio-plants by two-stage hyperimmunization producers of immunum. Hyperimmunization is carried out with increasing doses of antigens (vaccines) in a specific pattern. At the first stage, the vaccine is introduced (I-2 times), and further according to the scheme in increasing doses - a virulent culture of the production strain of microorganisms for a long time.

Thus, depending on the type of immunizing antigen, antibacterial, antiviral and antitoxic sera are distinguished.

It is known that antibodies neutralize microorganisms, toxins or viruses, mainly prior to their penetration into target cells. Therefore, in diseases when the pathogen is localized intracellularly (tuberculosis, brucellosis, chlamydia, etc.), it is not yet possible to develop effective methods of serotherapy.

Serum treatment-and-prophylactic drugs are mainly used for emergency immunoprophylaxis or elimination of some forms of immunodeficiency.

Antitoxic serums are obtained by immunizing large animals with increasing doses of antitoxins, and then toxins. The resulting sera are cleaned and concentrated, released from the ballast proteins, standardized by activity.

Antibacterial and antiviral drugs are obtained by hyperimmunizing horses with appropriate killed vaccines or antigens.

The short duration of the passive immunity formed is a disadvantage of the action of serum preparations.

Heterogeneous serums create immunity for 1-2 weeks, globulins homologous to them - for 3-4 weeks.

[35], [36]

Methods and procedure for the introduction of vaccines

There are parenteral and enteral routes of administration of vaccines and serums into the body.

With the parenteral method, the drugs are injected subcutaneously, intracutaneously and intramuscularly, which allows you to bypass the digestive tract.

One type of parenteral method of administering biologics is an aerosol (respiratory), when vaccines or serums are administered directly into the respiratory tract through inhalation.

The enteral method involves the introduction of biologics through the mouth with food or water. This increases the consumption of vaccines due to their destruction by the mechanisms of the digestive system and the gastrointestinal barrier.

After the introduction of live vaccines, immunity is formed after 7-10 days and lasts for a year or more, and with the introduction of inactivated vaccines, the formation of immunity ends by the 10-14th day and its intensity lasts for 6 months.

[37], [38], [39], [40]