SТIMULATION OF SIGNALING RECEPTORS GENE EXPRESSION AND INDUCTION OF SYNTHESIS OF CYTOKINES IN HUMAN BLOOD CELLS BY DRUG RIBONUCLEAT SODIUM AND ITS COMBINATION WITH INACTIVATED INFLUENZA VACCINES

DOI: https://doi.org/None

T.M. Sokolova (1,2), A.N. Shuvalov (1), V.V. Poloskov (1), I.M. Shapoval (1), M.P. Kostinov (3) 1 -N.F. Gamaleya Research Institute of Epidemiology and Microbiology, Gamalei str., 18, Moscow, Russian Federation, 123098; 2 -D.I. Ivanovsky Institute of Virology, Gamalei str., 16, Moscow, Russian Federation, 123098; 3 -I.I. Mechnikov Research Institute of Vaccines and Sera, Maly Kazenny by-street, 5A, Moscow, Russian Federation, 105064

Introduction. Russian drug Ribonucleate sodium (mixture of yeast ssRNA and dsRNA) possesses of the wide spectrum of antiviral and immunomodulation actions, it improves the efficacy of inactivated vaccines in experimental animals. It can activate IFN-system genes and enzymes in human cells. Inactivated vaccines have low levels of Immunogenicity in comparison with live vaccines so there is very actual to find optimal immunomodulators. The reactions of innate and adaptive immunity genes with drug Ribonucleate sodium were not studied previously.The aim of study. Studies of the effects of Ribonucleate sodium on signalling immunity factors genes (receptors TLR3, TLR4 and B2M), gene of Dicer I enzyme of RNA interference. Comparative analyses of these gene expression were made along with vaccines Gripol, Influvac and Vaxigrip in human blood cells. The spectrum of secreted cytokines (IFN-α, IFN-γ, IL1-β, IL10, IL17) was detected also. Methods. Gene expression analysis was made by real-time RT-PCR method. Induced cytokines were measured by using Eliza kits of «Vector-best» (Russia). Results. It was obtained the new information about gene modulation characteristics of Russian drug Ribonucleate sodium and its common effects with inactivated vaccines in human blood cells. Ribonucleate sodium is the potent activator of immune receptor genes TLR3 and B2M. These genes have very high sensitivity to low doses of dsRNA. Vaccines Gripol and Vaxigrip induce TLR4 and Dicer1 gene expression mainly, and stimulate B2M gene also. The dsRNA competes with vaccines for signaling pathways activation of TLR3 and TLR4 genes, but when using together, Ribonucleate sodium and vaccine Gripol, Influvac combinations result in more increased transcription levels of TLR3 and B2M genes than the one vaccine makes. Ribonucleate sodium induces high levels of Th1- and Th2secreted cytokines. Stimuli effects, observed with Ribonucleate sodium and vaccine combination, are related with the production of IFN-γ, IFN-α, TNF-α and IL10. Conclusion. It was shown the high potential of drug Ribonucleate sodium to stimulate signaling innate and adaptive immunity genes and to activate production of immunoregulatory cytokines as alone and so together with inactivated influenza vaccines. Combination with Ribonucleate sodium supplies the weak genes and cytokines activation by inactivated influenza vaccines Gripol and Influvac.
Keywords: 
immunity, Ribonucleate sodium, vaccines, gene expression, cytokines, influenza
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