Object of study: museum strains of pathogenic and non-pathogenic corynebacteria; bacterial antigenic preparations; native purified diphtheria toxoid; experimental combined diphtheria vaccines with bacterial component; post-vaccine humoral diphtheria immunity; nonspecific immune protection of the body. The purpose of the research: to substantiatе the development of an experimental combinated diphtheria vaccine based on diphtheria toxoid and bacterial adjuvant complex of native surface antigens of pathogenic corynebacteria aimed at improving the effectiveness of diphtheria vaccination. Methods of research: bacteriological, disintegration of microorganisms by physical factors, method of liquid gel chromatography, biochemical, serological, immunological, analytical and medical statistics. Equipment: electronic device Densi-La-Meter (PLIVA-Lachema, Czech Republic; inactivator LW-1, Memmert water bath without circulation WNB (Germany); ultrasonic devices USU-0707 "Retona", "Euro-biosonic" (Russia), Cole-Larmer (USA); Avanti J-26XP Beekman Coulter Centrifuge (USA); SF-56 Spectrophotometers Lomo-Spectrum (Russia), CARY-50 "Varian" (Australia); Gel Chromatography Equipment of LKV (Sweden), Ultracentrifuges Super Speed 65 MSE (England), Arthur Pfeiffer Wetzlar vacuum pump (Germany). The dissertation is devoted to substantiation of creation of a new combined antidiphtheria vaccine for improvement of the existing strategy of specific vaccine prophylaxis of diphtheria. To improve the effectiveness of diphtheria vaccine prevention, a combined diphtheria candidate vaccine with a bacterial component without the chemical adjuvant of aluminum hydroxide is proposed for the first time in the world. The technology of obtaining native surface antigenic complexes of diphtheria pathogen with adjuvant and immunogenic activity as biological platforms for a new class of parenteral and mucosal diphtheria vaccines was first developed based on the use of physical factors of bacterial disintegration. For the first time, the optimal productive mode of disintegration of microbial cells to obtain the preparation of C. diphtheriae surface antigens by ultrasound and ultra-high frequency electromagnetic radiation has been substantiated. For the first time it is shown that all experimental preparations of subcellular complexes of C.diphtheriae of four levels of microbial cell disintegration and degree of purification increase substantially diphtheria humoral immunity in parenteral, oral and combined vaccinations, but they differ in the degree of reactogenicity. Practical ways of preventing the development of skin reactions to an experimental combined diphtheria vaccine have been proposed and implemented. The efficacy of oral booster immunization as a part of the primary vaccination complex and with long-term (one-year) revaccination is shown. It is established that the basis of the anti-adhesive orientation of the combined candidate vaccine is the possibility of influence by physical factors on the adhesive properties of the culture of C.diphtheriae, as evidenced by the anti-adhesive activity of the serum of rabbits inoculated with experimental antigenic drugs. The anticolonization activity of experimental antigenic preparations by two-week monitoring of the elimination of the pathogen from the mucosa of the nose of rabbits vaccinated with the candidate vaccines and infected intranasally with culture of C.diphtheriae on the basis of the proposed method of transient bacterial carrier modeling is shown.The specific harmlessness of the experimental series of the studied diphtheria bacterial antigenic preparations obtained in the production conditions, in the tests of determination of general toxic and dermonecrotic action, as well as in the test of leukocytolysis, determination of the level of circulating immune complexes, is shown. Based on the application of physical factors of disintegration, the technology of obtaining native surface antigenic complexes of the diphtheria pathogen with adjuvant and immunogenic action as biological platforms for combined parenteral and mucosal diphtheria vaccines was developed. The optimal productive mode of disintegration of microbial cells to obtain the preparation of the surface antigen of C.diphtheriae is substantiated. The model of analytical-preparative unit for ultrasonic disintegration of microbial mass of production strain is proposed for production of native bacterial cell antigens in a single technological process in industrial production volumes. The degree of implementation: 3 patents, 6 acts of implementation. Sphere (industry) of use: health care (medicine: specific prevention of infectious diseases).
