POSSIBLE WAYS TO IMPROVE THE SAFETY OF DIPHTHERIAL VACCINES

Yelyseyeva I. V., Babych Ye. M., Zhdamarova L. A., Belozersky V. I., Kolpak S. A.

MICROBIOLOGY

Scentific article

Existing diphtheria vaccines cause local reactions (erythema, infiltration) from 10% and over 50% of vaccinations, the risk of which in frequency and severity increases with each subsequent booster dose of the vaccine, from early adolescence. The article is devoted to the development of approaches to increasing the safety of diphtheria vaccines by using oral booster immunization and replacement of the chemical adjuvant of aluminum hydroxide by bacterial antigen. The advantages of mucosal preparations are due to the stimulation of the immune response in general and locally, at the entrance gate of pathogens. Replacing the parenteral method of immunization with oral, which is characterized by naturalness, non-invasiveness, painlessness, does not psychologically traumatize, is also one of the possible ways to reduce the reactogenicity of the diphtheria vaccine. The refusal of the adjuvant of aluminum hydroxide in diphtheria vaccines and its replacement by an adjuvant of bacterial origin opens the possibility of avoiding the neurotoxic and autoimmune action of the chemical, increasing the immunogenicity of diphtheria toxoid, stimulating the Th1-cell defense of the organism, promoting the activation of innate immunity systems and anti-colonization resistance. Experimental rabbits were vaccinated with mono-preparations of native purified diphtheria toxoid (NPDT) and diphtheria vaccine AD-M, experimental combined vaccine preparations that contained bacterial antigens obtained from museum cultures C. pseudodiphtheriticum, C. diphtheriae var. mitis tox-, C. diphtheriae, var. gravis, tox+ by means of ultrasonic disintegration of microbial cells according to the author’s method. According to the RPHA with blood sera of rabbits vaccinated with the drugs studied, it has been shown that the oral route of vaccination makes it possible to obtain much more intense humoral immunity in comparison with subcutaneous vaccination even with primary dose of vaccine: the titers of antitoxic antibodies in the first-second week, respectively, were 8 and 5.6 times higher. The maximum level of antibodies in the initial oral administration of NPDT was obtained on the second week after inoculation –0.17 IU/ml, and with subcutaneous administration –in the fourth week –0.06 IU/ml. With the reintroduction of the NPDT, the advantage of the oral route of immunization became even more apparent: from the second week the levels of antitoxic antibodies differed by more than 100 times. The maximum titre of humoral immunity against diphtheria were revealed in the second and third week –21.3 and 16.0 IU/ml, respectively. At the same time, the subcutaneous administration of the NPDT made it possible to obtain the maximum level of antibodies –6.4 IU/ml in the first week after repeated vaccination, and then the antibody titers decreased from 0.2 to 0.06 IU/ml. The effective adjuvant effect of preparations of surface antigens of the C. diphtheriae cell wall of different degree of purification upon their introduction into the NPDT was demonstrated. The average geometric titres of antibodies in seropositive rabbits, according to the RPHA, obtained at the first, second and third weeks after vaccination, significantly exceeded the conventional protective level (0.1 IU/ml) by more than 2 times. In the control, with subcutaneous administration of the drug NODA (2 Lf), seroconversion did not occur during the whole experimental observation period.

diphtheria vaccines, safety, oral immunization, adjuvants, bacterial antigen

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«Bulletin of problems biology and medicine» Issue 1 Part 1 (142), 2018 year, 252-256 pages, index UDK 615.371: 579.871.1:615.06

10.29254/2077-4214-2018-1-1-142-252-256