The enteral (oral) method of vaccination has been developed since the time of L. Pasteur, who in 1880 expressed his opinion on the possibility of oral vaccination against anthrax. In the history of the development of this method, there were two ascents. The first of these is associated with the name AM Bezredki, with his concept of the role of local immunity in enteric immunization. The second upsurge in animal and human studies occurred in the 1960s, when the tests of enteric vaccines against tularemia, influenza, measles, mumps, tick-borne encephalitis, typhoid fever, whooping cough, botulism, tetanus, staphylococcal and adenoviral infections were successfully carried out, etc. Mass oral vaccination against polio is an excellent proof of the legitimacy of the very idea of enteric immunization.
In the intestine, there are favorable conditions for the penetration of soluble antigens and microorganisms (weakly alkaline medium, intense absorption, a well developed lymphoid apparatus, etc.). Good absorption is facilitated by a large area of the mucosa, which has villi, which in turn is covered with threadlike processes (microvilli), which increases the surface of the mucosa. The total area of the mucosa reaches 500 m2. The strongest absorption occurs in the jejunum and ileum. In the colon, absorption is weaker, in the rectum due to a well developed venous system, absorption occurs quickly and directly into the large circulation.
The gastrointestinal tract is an important organ of immunity. The lymphoid structure of the organ is made up of Peyer’s plaques, lymphoid tissue of the appendix, tonsils, regional lymph nodes. Lymph nodes are located on the outer surface of the intestine, in the mesentery and in the root of the mesentery.
Immunization with the oral administration of antigen begins in the upper parts of the digestive tract. Saliva has a weak effect on the antigenic properties of antigens, which manifest their activity already in the oral cavity and esophagus.
Prior to contact with the immune system, the vaccine must overcome a number of mechanical and chemical barriers, including the mechanical properties of the mucosa, the action of enzymes and the acidic environment of gastric juice. In this regard, the dose of antigen administered through the mouth should exceed by 100 or more times the dose sufficient for parenteral administration.
Saliva has a weak inhibitory effect on the vaccine, gastric juice causes the death of pathogens of certain infections, although living strains of poliovirus, enterovirus and intestinal bacteria are resistant to the action of gastric juice. Gastric and intestinal juices cause the decay of killed microorganisms and the cleavage of protein and polysaccharide antigens. Toxic properties of proteins are more resistant to the action of enzymes compared to their antigenic properties. In turn, vaccines entered enterally can change the composition, quantity and properties of digestive juices.
When oral vaccination develops local and general immunity, the body becomes resistant to infection through the mouth, skin, aerosol, etc.
In the mechanism of development of immunity in enteral vaccination, humoral and cellular factors play a role, as in other ways of introducing vaccines. The level of antibodies in serum with enteral immunization is often lower, and the development of general immunity is slower than with subcutaneous and intramuscular injection of antigen, although the final degree of resistance to infection with all vaccination methods may be the same. Moreover, local immunity with enteral administration of vaccines develops faster, so this method of vaccination can be used in practical medicine if it is necessary to quickly achieve specific stability in case of possible contamination through the mouth.
The history of enteral vaccines is estimated for decades, but only single enteric vaccines are used in practice. Among them, live poliomyelitis vaccine, recombinant rabies vaccine, widely used for the prevention of rabies in wild animals.
Oral vaccines against measles, typhoid fever, adenovirus and meningococcal infections, influenza, acquired immunodeficiency are being developed. Importance for the introduction of oral vaccines is important. For enteral immunization, high doses of vaccines are required, in many cases the antigen should be protected against destruction by gastric juice with an acid-fast coating, which naturally increases the cost of vaccines. The forms of release of enteral vaccines can be different, they can be liquid or dry, have the form of dragees, tablets, capsules, pills, etc.
Thus, there is no universal method of vaccination. In the practice of health, several methods of administering vaccines are used: subcutaneous, intramuscular, enteral, aerosol, and needle-free. It must be admitted that the enteral method of vaccination seems the most promising. When administering vaccines through the mouth, one can get immunity to any infection. Enteral vaccines have low reactogenicity and low allergenicity. They are well tolerated, their immunological and epidemiological efficacy is not inferior to similar vaccines administered in another way. The oral method is safe and simple, does not require special conditions, equipment and apparatus. Vaccination can be carried out in any conditions, it lacks the drawbacks of syringe and aerosol methods, with no danger of transmission of infections, it does not cause negative emotions in vaccinated.
Immunization of a person through the intestines and the respiratory tract is a physiological way of acquiring a specific resistance to infectious diseases. Contact of the pathogen with the mucosa is important for the initial stage of infection and the process of natural immunization.
In this regard, two areas for the development of new vaccines are being developed. One of them is associated with an adhesive protein, which is located at the ends of the filaments of the hair located on the surface of the bacteria. With the help of pili bacteria are attached to the mucosa, this ensures the colonization of bacteria on the mucosa.
Immunization with a vaccine prepared on the basis of an adhesin or the introduction of ready antibodies against this protein hinders the colonization of bacteria on the mucosa and the development of the infectious process.
Another direction is associated with the use of a nontoxic portion of a cholera toxin (CTB) or a thermolabile toxin E. Coli (LTB) as carriers and delivery vehicles of other antigens conjugated to these carriers. PTS and LTB have the ability to interact with mucosal receptors and thus provide a long-term presence of antigens on the mucosa, promote the transfer of antigens through the mucosa and the development of an immune response. Such experimental “mucosal” vaccines have been obtained for many types of pathogens of infectious diseases.
In recent years, such concepts as mucosal immunity, mucosal vaccines (see Section 34.3), mucosal system have been formed. The mucosal system includes gastrointestinal, respiratory and urogenital tracts, as well as lacrimal, salivary and mammary glands.
Antigens enter the lymphoid tissue of the intestine mainly through the epithelium of Peyer’s plaques. Mechanisms of penetration of antigenic material through the intestinal mucosa may be different: the intercellular pathway of the antigen itself, the same pathway with phagocytes containing the antigen, penetration through the cytoplasm of the cell or through mucosal defects. Epithelial cells possessing pronounced pinocytic properties, process antigenic material and transmit it to lymphocytes. Antibody-forming cells are located in the own plate of the intestinal mucosa. The ratio of plasma cells secreting 1dA, 1dM and IgG is 20: 3: 1. Ticles with cytotoxic markers are concentrated in the epithelium.
1-5% of the protein administered with food is not cleaved by the enzymes of the gastrointestinal tract. Part of the uncleaved protein (egg white, milk protein, heterologous globulin, etc.) is absorbed into the lymphatic system. At the heart of absorption are not only the mechanisms of filtration, diffusion and osmosis. Through the intestinal mucosa penetrate the killed and living microorganisms (viruses, bacteria, rickettsia) belonging to the group of enteropathogenic or other, different in the mechanism of transmission and localization of infections, groups of pathogens. The attachment of microbes to the epithelial cells and their subsequent invasion depend on the adhesive antigens of the microbes and the presence on the epithelial cells of the corresponding receptor zones. Strong invasive properties are Salmonella, Shigella, Campylobacter, Yersinia enterocolytica. In the intestine there is a persistence of a living virus.
The resulting IgA passes into the lumen of the intestine through epithelial cells in the form of a two-dimensional shape. Its acepies are bound by a stiffness, which has an affinity for the glycoprotein, which is formed in epithelial cells. This secretory component of the complex protects IgA from the action of enzymes, and the secretory IgA itself prevents the adhesion of bacteria and viruses to the surface of the mucosa, neutralizes toxins and activates the phagocytic activity of cells. In the secretory fluid, the IgAiIgG ratio is 1: 1, while in the serum it corresponds to 1: 6.
Antigens and sensitized lymphocytes can penetrate the regional lymph nodes into the chest stream and blood vessels, settle in the lymphoid organs and induce the formation of antibodies of different classes. Cells that synthesize IgA, return to the intestinal mucosa, strengthening local immunity.
An important mechanism of anti-infective immunity is the entry of IgA into the intestine through the liver. Hepatocytes capture IgA (its two and polymeric forms) from circulating blood and excrete it in bile. This greatly increases the resistance of the organism to food coming from food microbes.
Non-parenteral methods of vaccination, other than oral and inhalation, include intranasal, conjunctival, as well as percutal and intravaginal routes. In the last two cases, vaccines are given in the form of candles. A great future for “edible” vaccines, which are created on the basis of transgenic plants.