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Background. Currently, the COVID-19 pandemic in the world and in Russia remains the main event. In this regard, the study of the manifestations of the epidemic process of the new coronavirus infection COVID-19 and the patterns of its development are an urgent area of research. In the fight against this viral disease, an important role is assigned to the study of the development of population immunity to the SARSCoV-2 virus, which will make it possible to assess the dynamics of seroprevalence and the formation of post-infectious humoral immunity, forecasting the development of the epidemiological situation, elucidating the characteristics of the epidemic process, and will also contribute to planning activities for specific and non-specific prevention of the disease.The aim: to determine the dynamics of population immunity to SARS-CoV-2 among the population of the Irkutsk region during the COVID-19 pandemic.Materials and methods. As a part of the Rospotrebnadzor project of assessing population immunity to SARS-CoV-2 in the population of the Russian Federation, the research has being conducted among the population of the Irkutsk region in the periods from June 23, 2020 to July 19, 2020 (Stage 1), from September 16, 2020 to September 25, 2020 (Stage 2), from December 7, 2020 to December 18, 2020 (Stage 3) and from March 8, 2021 to March 14, 2021(Stage 4), taking into account the reacted one recommended by the WHO. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of tests for human serum or plasma for specific immunoglobulins of class G to the proteins of the SARS-CoV-2 coronavirus.The results. The research of the humoral immunity of volunteers shows that during the period of an epidemic rise in the incidence of COVID-19 in the Irkutsk region, a low level of seroprevalence was formed (Stage 1 – 5.8 ± 0.5 %, Stage 2 – 12.1 ± 0.7 %), and in conditions of a long-term maximum increase in the incidence rate – 25.9 ± 1.0 % (Stage 3) and 46.2 ± 1.2 % (Stage 4). A significant proportion (Stage 1 – 82.2 ± 3.2 %, Stage 2 – 86.1 ± 2.3 %) of asymptomatic forms of infection characterizes the high intensity of the latently developing epidemic process in the first two stages. High levels of IgG in reconvalescents of COVID-19 persisted for an average of 3 to 5 months.Conclusion. The results of assessing the population immunity to the SARS-CoV-2 virus in the population of the Irkutsk region indicate that the seroprevalence level at Stage 4 of the research was 46.2 %. After the disease, on average, 49.5 % of persons did not detect antibodies. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity.

Background. Improving the methodology of immunological monitoring in natural foci of plague in the Russian Federation and adjacent territories to increase the effectiveness of epidemiological surveillance of plague is an urgent line of research. The lack of correlation between the production of specific antibodies to the capsular antigen (F1) ofthe plague microbe with other indicators of the state of cellular defense reactivity indicates the need to search for new informative and accessible markers for assessing anti-plague immunity.Objective: to evaluate possibility of using the complex preparation (F1 and cell membranes) evaluate the possibilities of using an artificial antigenic complex based on F1 and cell membranes (CM) of the plague microbe in antigen-specific tests in vitro in people vaccinated against plague.resu. The study involved 153 volunteers living in the territory enzootic for plague (the village of Khandagayty ofthe Ovyur kozhuun of the Tyva Republic and the village of Kosh-Agach of the Kosh-Agach district of the Altai Republic). The study included the determination of spontaneous and mitogen-induced production of cytokines (IFN-γ, IL-4, TNF-α) by blood cells, titers of specific IgG antibodies to the capsular antigen F1 of the plague microbe and concentrations ofthe main classes of immunoglobulins (IgM, IgG, IgA and IgE) in blood serum, as well as immunophenotyping of blood lymphocytes (CD3, CD4, CD8, CD16, CD19).Results. Comparative assessment of the level of cytokines (TNF-α, IFN-γ and IL-4) in spontaneous/induced F1+CM Y. pestis tests revealed a statistically significant increase in the production of cytokines TNF-α and IFN-γ in the antigeninduced tests compared with spontaneous (p < 0.01).Conclusion. Thus, the effectiveness of the use of artificial antigenic complex based on F1 and cell membranes ofthe plague microbe has been shown to assess the production of cytokines in antigen-specific cell tests in vitro, which justifies the need for further research.

Background. The ongoing COVID-19 pandemic in the world and in Russia remains the main event in 2020. A comprehensive study of the patterns of development and manifestations of the epidemic process of the new coronavirus infection COVID-19 is an urgent line of research. One of the important aspects of the fight against COVID-19 is the study of population immunity to the SARS-CoV-2 virus in order to assess seroprevalence and the formation process of post-infectious humoral immunity to SARS-CoV-2, forecast the development of the epidemiological situation, identify the features of the epidemic process, as well as planning measures for specific and non-specific disease prevention. The aim of the research is to determine the level and structure of population immunity to SARS-CoV-2 among the humans of the Irkutsk region during the COVID-19 epidemic. Materials and methods. As part of the Rospotrebnadzor project to assess population immunity to SARS-CoV-2 in the population of the Russian Federation, research is being conducted among the population of the Irkutsk region in the periods from 06/23/2020 to 07/19/2020 (stage 1), from 09/16/2020 to 09/25/2020 (Stage 2) and from 12/07/2020 to 12/18/2020 (stage 3), taking into account the reacted one recommended by the WHO. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of tests for human serum or plasma for specific immunoglobulins of class G to the nucleocapsid of the SARS-CoV-2 virus produced by FBUN GNCPMiB Rospotrebnadzor (Obolensk). The results of a research of the humoral immunity of volunteers show that during the period of an epidemic rise in the incidence of COVID-19 in the Irkutsk region, a low level of seroprevalence was formed (stage 1 – 5.8 ± 0.5%, stage 2 – 12,1 ± 0,7%), and in conditions of a long-term maximum increase in the incidence rate ¬– 25,9±1,0% (stage 3). A significant proportion (stage 1 – 81,2±3,2%, stage 2 – 90.9 ±1,9%) of asymptomatic forms of infection characterize the high intensity of the latently developing epidemic process in the first two stages. High levels of IgG in reconvalescents of COVID-19 persisted for an average of 3 to 4.5 months. Conclusion. The results of assessing the population immunity to the SARS-CoV-2 virus in the population of the Irkutsk region indicate that the seroprevalence level at the 3rd stage of the research was 25.9%. After the disease, on average, 41.6% of persons did not detect antibodies. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity.

Background. Currently, during the COVID-19 pandemic, one of the most pressing healthcare problems is to ensure the safety of the population of the Russian Federation. There is insufficient information on the duration and intensity of post-infectious immunity in relation to SARS-CoV-2, especially in case of inapparent (without clinical signs), mild or latent forms of infection.Materials and methods. The study involved 99 volunteers with a laboratory confirmed PCR diagnosis of COVID-19 who were residents of the Irkutsk Region and of other regions of the Russian Federation and arrived to work in Bodaybo on a rotational basis. Also the study included 50 conditionally healthy people living in Irkutsk who had negative PCR results for SARS-CoV-2 RNA presence.Specific IgG and IgM antibodies to SARS-CoV-2 were detected in blood serum by enzyme-linked immunosorbent assay (ELISA) using test systems “ELISA anti-SARS-CoV-2 IgG” (FBUN SSC PMB, Obolensk, Russian Federation), “SARS-CoV-2-IgG-IFA-BEST” and “SARS-CoV-2-IgM-IFA-BEST” (Vector-Best, Novosibirsk, Russian Federation).Results. The results of a study of the humoral immunity of patients with asymptomatic and clinical forms of COVID-19 are presented. The data indicate the production of specific IgG in the blood serum of people in 2–3 weeks after SARSCov-2 infection and reaching its maximum level on the 20–21st day. The seroconversion rate was 94.9 %. It was shown that the geometric mean titer of antibodies in asymptomatic and mild forms of coronavirus infection did not differ statistically and amounted to 1:512 and 1:632, respectively. Higher titers of antibodies (1:1600) were detected in the moderate form.Conclusion. The research results can serve as a basis for studying the dynamics of changes in the indicators of the humoral immune response in patients with COVID-19 and for clarifying the duration of their post- infectious immunity in order to predict the development of the epidemic situation and to ensure the planning of specific prevention.

Background. Plague is an especially dangerous natural focal infectious disease belonging to a group of quarantine infections. There are eleven natural plague foci in Russian Federation. In Republic Tyva plague endemic territories include Ovyur, Mongun-Taigin and Tes-Hem areas where Y. pestis strains are intermittently isolated from Citellus undulates. Population living at the territory of the natural foci get immunoprophylaxis against plague at complication of epizootic and epidemic conditions.This paper presents the results of monitoring indicators of the immune status of people vaccinated with the plague vaccine living in the territory of the Tuva natural focus.Materials and methods. The study involved 76 volunteers who had not previously been vaccinated. The study included the determination of production IFN-γ, IL-4, TNF-α by blood cells, titers of specific IgG antibodies to the capsule F1 antigen of the Yersinia pestis, and concentrations of immunoglobulins in serum blood, as well as immunophenotyping of blood lymphocytes.Results. In the course of a comprehensive immunological study, features of the development of cellular and humoral reactions in people living in the territory of the Tuva natural plague focus were established in the first months after vaccination. Changes in the concentration dynamics of the main classes of immunoglobulins were accompanied by an increase in the level of specific IgGs to the F1 within 6 months after immunization. In the same period, a significant increase in the production of cytokines, as well as significant changes in terms of the subpopulation composition of the vaccinated blood.Conclusion. It is necessary to note the importance of studying of the human immune status in 1–3 months after plague vaccination as this period coincides with potentially dangerous season from epidemiological point of view. Nevertheless, much important role for improvement of tactics of the specific prevention measures plays the data received after the revaccination.

Aim. To study the subpopulational structure of blood cells of the experimental animals immunized with thermoextracts (TE) of Brucella abortus in L- and S-form. Materials and methods. Total 100 certified («Vector», Novosibirsk) outbred mice were immunized with B. abortus I-206 TE in L- and S-form in 20 μg protein dose. After 1, 3, 7, 14 and 21 days of observation the phenotypes (CD45, CD3, CD4, CD8, CD19, CD69) of blood cells were detected. Results. General regularities were revealed after injection of the experimental preparations. So, B. abortus TE in L- and S-form caused the immune response that increased granulocyte number and expression of early activation marker CD69 by T- and B-lymphocytes of blood in early period of observation (1-3 days), decrease in general B-lymphocyte content in late periods of observation (7-21 days). Thus, mice received B. abortus ТE in L-form demonstrated authentically higher CD69 expression of blood lymphocyte subpopulations than mice received B. abortus ТE in S-form. Distinctions in formation of humoral immune response were revealed that probably was connected with alteration of Brucella chemical composition in the course of L-transformation. Conclusion. The investigation established that B. abortus TE in L- or S-form caused immunological reorganization in the experimental animal organisms. On the basis of the fin

Introduction. The current direction in medicine is the creation of immunobiological preparations to increase the effectiveness of specific immunotherapy and immunoprophylaxis, containing immunomodulators in their composition. These natural or synthetic substances can have a regulating effect on the immune system. At present, water-soluble organic-inorganic polymeric materials with nanoparticles of various chemical substances with bactericidal and immunomodulating properties can serve as such promising compounds.The aimof the work is to study the acute toxicity of polymer nanocomposites based on 1-vinil-1,2,4-triazole copolymer with N-vinylpyrrolidone with silver, gold and selenium nanoparticles and their effect on the functional state of immune system cells in vitro.Materials and methods.The study of acute toxicity was performed on outbred white mice. The activity of superoxide dismutase and glucose-6-phosphate dehydrogenase were studied in guinea pig peritoneal macrophages. The study of spontaneous and nanocomposite-induced production of pro- (interferon gamma and tumor necrosis factor alpha) and anti-inflammatory (interleukin-4) cytokines by blood cells was carried out using clinical material obtained from volunteers using the ELISA method. Results. It has been established that nanocomposites with silver and gold nanoparticles do not cause the death of white mice, their temperature increase and body weight decrease. The average lethal dose for a nanocomposite with selenium nanoparticles was determined as 1 gram per 1 kilogram of animal mass. It was shown that the tested nanocomposites have a stimulating effect on the production of cytokines by human blood cells in vitro. It was established that a nanocomposite with selenium nanoparticles increases the activity of superoxide dismutase and glucose-6-phosphate dehydrogenase. A comparative analysis of their actions with the actions of commercial preparations of biological origin, with immunomodulatory properties.Conclusion. The data obtained allow us to substantiate the need for further research on the effects of nanocomposites based on 1-vinyl-1,2,4-triazole copolymer with N-vinylpyrrolidone with silver, gold and selenium nanoparticles on the macroorganism in both in vitro and in vivo conditions.

Background. Plague is a dangerous natural-focal bacterial disease that can cause emergencies of interstate significance. In 2014–2016, three bubonic plague cases were registered among local residents in the Republic Altai. This circumstance was the reason for implementation of complex preventive measures. Comprehensive studies of the immune status of humans vaccinated (revaccinated) with live plague vaccine are presented in this paper. These people constantly reside and work at the territory of Gorno-Altai high-mountain natural plague focus. Methodology. The study of the clinical material (blood) from 60 volunteers included the determination of the functional activity of phagocytic cells, the production of IFN-γ, IL-4 and TNF-α cytokines, the titre of specific IgG anti-bodies to the capsular antigen of the plague microbe and the concentrations of the main classes of immunoglobulins in blood serum by enzyme immunoassay, as well as immunophenotyping of blood lymphocytes through flow cytometry and the de-termination of the alleles of HLA class II genes by a polymerase chain reaction. Results. The materials of these studies made it possible to determine a number of important parameters indicative of the cellular and humoral immunity activation in humans immunized against plague. Frequently occurring alleles of the HLA-DRB1, HLA-DQB1 and HLA-DQA1 genes were defined. Possible associations of these alleles with the levels of TNF-α and IL-4 production, as well as with the relative content of T-helpers and CD3-CD16+ cells were revealed. Conclusions. The obtained results indicate the immune reconstruction of the humans immunized against the plague. The immunological efficiency and safety of live plague vaccine were confirmed during the exacerbation of the epidemiological situation in active natural plague focus. Nevertheless, further immunological monitoring is necessary to fully characterize the immunological reactivity of the humans vaccinated (revaccinated) with live plague vaccine, and to improve the strategy for specific plague prevention in natural foci.

Aim. To study the subpopulational structure of blood cells of the experimental animals immunized with cellular walls (CW) of Francisella tularensis different subspecies. Materials and methods. Total 210 certified («Vector», Novosibirsk) outbred mice were immunized with CW preparations of F. tularensis different subspecies in 95 pg protein dose. After 3, 7, 10, 14 and 21 days of observation the phenotypes (CD45, CD3, CD4, CD8, CD19, CD69) of blood cells were detected. Results. Dynamics of leukocyte balance in experimental animals depended on F. tularensis subspecies. All studied preparations promoted development of cellular and humoral immunity that confirmed by the increase of monocytes and B-lymphocyte, and also by the expression of CD69 activation marker. CW of F. tularensis subsp. mediasiatica А-61 promoted higher activation of cellular immunity in experimental animals in comparison with other preparations. Probably, exactly this factor causes its high immunogenic activity (83 % survival rate). Conclusion. On the basis of the results there is a necessity to further detailed research of CW immunogenic properties of F. tularensis subsp. mediasiatica А-61 as a perspective component in design of a tularemia vaccine.

Some data of the complex immune status study of humans vaccinated with live plague vaccine EV are represented. These people constantly reside and work at the territory of Gorno-Altai high-mountain natural plague focus that today demonstrates high epidemic activity. It was shown that 93% of the vaccinated humans developed positive seroconversion in 1 month after immunization, but after 6 months the protective antibody titers significantly decreased and did not exceed the diagnostic level. At the same time the revealed changes of the main immunoglobulin concentrations ranged within the physiological norm. Furthermore, increased production of TNF-and IFN- in blood cells in 1 month after vaccination may indicate the development of cellular immune response in humans immunized against plague and confirms the predominant role of cellular response in comparison with humoral reactions.

Relevance. The vast majority of the virulence factors of Yersinia pestis is determined by genes of plasmid. The genome of the plague pathogen Altai subspecies Y. pestis subsp. altaica has three plasmids: pYV, pYP and pYT. Plasmids pYV Yersinia strains exhibit phenotypic traits, the effect of which is aimed at the suppression of the phagocytic activity of the cells of the immune system. Species-specific plasmid pYP determines synthesis bacteriocine (pesticin 1) and plasminogen activator, and plasmid pYT - murine toxin and a capsular antigen F1. Loss of one or more plasmids leads to a change of the pathogenic properties and a reduction or even total loss of the virulence of the pathogen, as well as affect the functional state organs of the immune system. Goal. To reveal characteristics of subpopulations of blood cells of experimental animals infected with Y. pestis containing various plasmids Materials and methods. The study was conducted on 370 white improved conventional mice with standard of content and weight (17 -19 g). As objects of study used 7 strains of Y. pestis from the collection of the museum of living cultures of the Irkutsk Scientific Research Anti-Plague Institute: Y. pestis subsp. altaica I-2948/3, Y. pestis subsp. altaica I-2948, Y. pestis subsp. altaica I-2359, Y. pestis subsp. I-3560 pestis, Y. pestis subsp. I-3480 pestis, Y. pestis subsp. I-2638 pestis, Y. pestis subsp. pestis I-3479. Results. Immunograms analysis showed that changes in the composition of blood cells in experimental animals depends on plasmids of the strain and time of observation. Importantly, the infectious process induced strains with a complete set of plasmids (Y. pestis subsp. pestis I-3560, Y. pestis subsp. pestis I-2638), is accompanied by significant changes in cell populations, as the causative agent of plague blocking barrier system key mechanisms innate immunity and prevents the formation of high-grade microorganism adaptive immunity. Conclusions. Are established features of subpopulation structure of blood cells of white mice, infected with strains of the main and Altai subspecies and their isogene options which are associated with a plasmid profile of a plague microbe. Strains of Y. pestis subsp. pestis of I-3479 and Y. pestis subsp. pestis of I-3480 can be recommended for further studying as perspective as vaccinal.

Displayed are the results of examination of immuno-competent local population of the Khabarovsk Territory, the Jewish Autonomous Region, the Amur Region, as well as foreign residents living and temporarily working in the areas, on a wide range of natural-focal bacterial and viral infectious diseases including the causative agents of some “exotic” infections too. Investigations have been carried out with the participation of experts from the specialized anti-epidemic team No. 1 (Irkutsk Research Anti-Plague Institute), who worked in the Amur Region, and a group of laboratory-epidemiological specialists from the team No. 2 - deployed in the Khabarovsk Territory and the Jewish Autonomous Region during the flooding in August-September 2013. The total of 1335 blood sera samples has been tested using serological methods. The findings have revealed the presence of immuno-competent population in the three regions of the Far Eastern Federal district in reference to the agents of natural-focal infectious diseases: tularemia, leptospirosis, yersinioses, hemorrhagic fever with renal syndrome, human granulocytic anaplasmosis, tick-borne borrelioses, tick-borne viral encephalitis, Californian encephalitis serogroup, Sindbis, West Nile and Dengue fevers. Circulation of Batai and Crimean-Congo hemorrhagic fever viruses has not been revealed based on serological assays.

For the first time ever mobile SAET units have performed complex investigation of epidemiological situation on leptospiroses in order to provide sanitary-epidemiological welfare of the population in the Amur-River region devastated by high water in 2013. Analyzed have been contemporary published and archival data on morbidity rate and epizootic activity of the natural leptospirosis foci in the Amur-River territory up to 2013. Summarized is the information concerning monitoring over natural focal infections (in particular leptospiroses) in the flooding area, obtained by specialized antiepidemic teams from Irkutsk Research Anti-Plague Institute of Siberia and Far East deployed in Belogorsk town of the Amur Region and Khabarovsk city in 2013. Epizootiological situation during the high water period in the Jewish Autonomous Region has been defined as an extremely adverse, unlike the Khabarovsk Territory and the Amur Region where epizootic process is less expressed. Therewith aggravation of epidemiological situation on leptospiroses in the Amur-River Region in 2014 is not ruled out.

Influence of Francisella tularensis lipopolysaccharide preparations on morphological changes in immunocompetent experimental animals was studied by subcutaneous introduction using survey microscopy and morphometric methods. Low expressed activation of B- and T-dependent bands in immunocompetent organs was determined. Proliferation of antigen-presented cells at early stages of investigation indicates the cell immunity activation. Pathomorphological alterations caused by lipopolysaccharide inoculation are homogeneous and benignant.

Experimental preparations of the lipopolysaccharide (LPS) of Francisella tularensis of four subspecies (tularensis, holarctica, mediasiatica, novicida) were obtained using Tween extraction method. Physical and chemical characteristics of the obtained preparations are presented. Examined was the effect of tularemia agent of different subspecies upon the phagocytic part of the experimental animals` immunity in vitro. LPS biomolecules demonstrated weak stimulating effect upon oxygen- and nitroxide-dependent bactericidal systems and lacked cytopathogenicity for phagocytes apoptosis activation. The obtained results suggest that such inactivity of tularemia agent LPS is associated with its structural peculiarities.

Carried out were epizootiological studies of the flooded areas of the Amur Region, the Khabarovsk territory, and the Jewish autonomous region in order to investigate the situation on tularemia in view of the river floods in August-September, 2013. Involved were specialized anti-epidemic teams from Irkutsk Research Anti-Plague Institute for works at the site of emergency. Therewith, analysis of the data of the epizootiological examination of the territories obtained in cooperation with specialists from the Rospotrebnadzor local Centers of Hygiene and Epidemiology, and results of laboratory investigations with application of bacteriological, immu­no­bio­logical and molecular-genetic methods indicated insignificant epizootic and epidemic activity of the natural tularemia foci. Given is the conclusion on epizootiological-epidemiological condition for tularemia in the flooded areas of the Amur River region and a short-term epizootiological forecast for 2013-2014, as well as recommendations concerning stabilization and improvement of epidemiological conditions in the region.

Analysis of molecular-biological mechanisms of patho-, immuno- and morphogenesis allowed to determine the role of bactericidal mechanisms (oxygen-, nitroxide-related and oxygen-free) of tularemia microbe phagocytosis by immunophagocytic system cells. Using PCR with primers pdpD-1F, pdpD-1R, pdpA 1, pdpA2 it was shown that the structure of pathogenicity islands (FPI) in F. tularensis strains of different subspecies depended upon what subspecies the strain belonged to, and was probably associated with tularemia microbe virulence. The macroorganism reaction to the introduction of tularemia microbe of different subspecies was evaluated. The obtained data were of prognostic significance for characterization of infectious process course and for the development of criteria for lymphoid organs response in pathologic and adaptive processes.