Vol 98, No 2 (2021)

Introduction. Since the development of inactivated polio vaccines, different stages of the production process have been changed and improved. Current production of inactivated polio vaccines based on both wild and attenuated strains includes several technological stages, one of which is the concentration of the virus-containing liquid, which ensures poliovirus concentration, and purification of the virus-containing liquid from a significant part of the ballast components.

Research objective is to compare the characteristics of ultrafiltration membranes and select the membranes that provide optimal value of purification and concentration of poliovirus type 1 (Sabin strain).

Materials and methods. Laboratory ultrafiltration systems from two manufacturers with 50, 100, and 300 kDa membranes were used for the concentration. Results were evaluated by the content of total protein, which is the main stress for the subsequent purification stages, the value of infectious virus titer in the concentrate, and the content of D-antigen as the target product.

Results and discussion. Obtained results demonstrated that the content of the target product (the highest D-antigen content) and purification from impurity proteins (the total protein content in the concentrate) were most optimal when a membrane with a cut-off of 300 kDa was used for concentration. The study also evaluated the real cut-off components by various membranes to determine the composition of the protein load on the target product.

Conclusion. In terms of quality of the resulting target product and the manufacturability of the production process, the use of a 300 kDa membrane is the most appropriate when working out the technology for manufacturing inactivated polio vaccine based on Sabin strains of poliovirus and the Vero line as a producing culture.

Aim. To characterize the intracellular expression of cytokines by spleen T-helpers and the spontaneous production of cytokines in the blood of BALB/c mice immunized with Yersinia pestis EV NIIEG against the background of immunomodulation.

Materials and methods. Intracellular expression of CD4⁺IFN-γ⁺, CD4⁺IL-4⁺, CD4⁺IL-17⁺ was determined in mice spleen cell suspensions by flow cytometry, IFN-γ and IL-10 were measured in ELISA in blood supernatants on day 3 and day 21 after the immunization with Y. pestis EV against the background of immunomodulation. On day 21 after the immunization animals were infected by Y. pestis 231 at a dose of 400 LD50.

Results. Differences in cytokine response to studied drugs, correlated with CD4⁺IFN-γ⁺ levels in animals, were identified. On day 3, a significant decrease in CD4⁺IFN-γ⁺ was observed in response to Y. pestis EV and to recombinant gamma interferon (Ingaron). A significant increase in CD4⁺IFN-γ⁺ was detected in response to vaccine strain administered with azoximer bromide (Polyoxidonium). Intracellular expression of IFN-γ, IL-4 and IL-17 increased on day 21by an average of 2,3 times when immunomodulators were used in the immunization schedule. In addition, on day 21 a significant (p ˂ 0.05) increase in the proportion of T-helpers expressing IFN-γ, as well as in level of spontaneous IFN-γ production in blood supernatants was observed only in animals immunized by schedules that included immunomodulators. After the challenge with Y. pestis 231 of animals previously immunized by schedules that included Polyoxidonium, the correlation analysis confirmed the association (r = 0,94; p = 0,0004) of mice survival with intensity of CD4⁺IFN-γ⁺ expression.

Conclusion. The data obtained confirm the effectiveness of Polyoxidonium application in experimental animal Y. pestis EV immunization schedule and the usefulness of intracellular cytokine expression measurement for assessment of the level of protection following the immunization.

Purpose. A dynamic comparative analysis of the results of identification of Vibrio cholerae (V. cholera) isolates from water and human specimens isolated during the monitoring of cholera throughout the Russian Federation in 2013–2019.

Materials and methods. Total 385 strains of V. cholerae O1 serogroup (including one toxigenic V. cholerae O1 El Tor Inaba — Rostov region, 2014) and the R-variant from environment objects were identified in the territory of 21 regions of the Russian Federation.

Results. It was found that 91% of the strains were isolated in 7 regions of the Russian Federation: Republic of Kalmykia, Krasnodar Krai, Transbaikal Krai, Khabarovsk Krai, Primorsky Krai, Rostov region and Irkutsk region. 2.3% of strains were atypical in their agglutinability, and 75.3% of strains had atypical phagosensitivity. Phagotypes were identified for 13.2% of strains isolated in 11 administrative territories. Phageotype 11 included 48.8% of the strains isolated mainly in the Transbaikal Krai. Non-toxigenic strains of V. cholerae nonО1/nonO139 (n = 46) were isolated from 43 patients with acute intestinal infections and otitis in 8 regions of Russia. PCRtyping of 377 non-toxigenic V. cholerae strains demonstrated that they belong to 13 clusters and 71 genotypes. Strains with unique genotypes (probable cases of importation) and with the same genotypes repeatedly isolated in different years in one or several territories of the Russian Federation were identified, indicating the prevalence of strains in environment throughout the country.

Conclusion. The results allowed us to characterize the epidemiological situation of cholera in Russia (in terms of the environment contamination with V. cholerae O1) as unstable, but not significantly changed over the past 7-year period. These data are important for substantiating the forecast for further development of the epidemiological situation.

The problem of choosing a strategy to control hepatitis A in the Russian Federation remains relevant for the health care of our country. By strategy we mean a scientifically based program of action that defines the priorities and resources needed to effectively control hepatitis A.

The aim of the work is to present a strategy to control hepatitis A in the Russian Federation, taking into account the realities of today. Based on the analysis of Russian and international studies, we present answers to the questions that should be addressed before the choosing a strategy to control hepatitis A in the Russian Federation. The low incidence of hepatitis A creates a false image of the favorable situation with this infection. The rationale is given to include vaccination against hepatitis A in the National Vaccination Schedule in the section of mandatory vaccinations. Routine vaccination of children aged 24 and 36 months will lay the foundation for future protection against this infection. We consider the creating a National Hepatitis A Vaccination Program as an important aim. The implementation of such a program will allow full control of hepatitis A in the Russian Federation.

The review provides information on single nucleotide polymorphisms (SNPs) in genes encoding some interleukins belonging to the interleukin-1 (IL-1) superfamily and on their association with different infectious and non-infectious human diseases. It also briefs on the history of SNP discovery and the progress in the related scientific studies till the present time. It gives an insight into some mechanisms of interaction between infectious agents and the human immune system, involving SNPs in some cytokines of the IL-1 superfamily. The review provides data on relationships of SNPs in genes encoding other factors of the immune system, which are associated with the specific characteristics of natural history of chronic hepatitis B and C. It explores the significance of assessment of the SNP-proportion in proinflammatory cytokines and their antagonists of the IL-1 superfamily among the healthy population as well as the ratio of individual SNPs in specific groups of patients as a monitoring parameter for epidemiological surveillance of infectious diseases.

The second part of the literature review on the role of intestinal microbiota disturbances in the pathogenesis of autism spectrum disorders (ASD) is devoted to the analysis of published literature on the possible mechanisms underlying the impact of intestinal dysbiosis on the function of the central nervous system and symptoms of ASD and vice versa, the effect of the nervous system on the intestinal microbiota. The hypotheses of slow inflammation, hyperserotoninemia, the production of toxic metabolites of the intestinal microbiota, impaired intestinal wall permeability, and the effect of intestinal dysbiosis on the synthesis of amino acids, vitamins and other biologically active substances that are potentially involved in the etiology and pathogenesis of ASD are considered. Available to date experimental and clinical data supporting these hypotheses are presented. The main mechanisms of the so-called gut-brain axis, which may be related to the pathogenesis of ASD, are formulated.

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