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One of the important directions for increasing the immunogenic properties of vaccine strains against highly dangerous infections is the search for adjuvants that not only stimulate the immunological effectiveness of vaccination, but can also provide a metabolic correction of the vaccination process. Organoselenium compounds have immunotropic properties and an antioxidant effect, and therefore, the study of the effect of the organoselenium compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the activity of the TLR2 and TLR4 gene expression by macroorganism cells of experimental animals immunized with Yersinia pestis EV NIIEG vaccine strain, is a current area of research.The aim of the work. To assess the TLR2 and TLR4 gene expression by cells of the immune phagocyte system of experimental animals immunized with the Y. pestis EV vaccine strain against the background of immunomodulation with the organoselenium compound 974zh.Materials and methods. The study was carried out on 125 certified outbred white mice. Biological material (blood, spleen) was disinfected, and the spleen was homogenized. RNA isolation and reverse transcription were performed using commercial reagent kits. The expression level of the TLR2 and TLR4 genes was determined using real-time polymerase chain reaction with specific primers.Results. When assessing innate immunity using the example of blood and spleen cells of animal models, features of the TLR2 and TLR4 gene expression were revealed in response to the introduction of the Y. pestis EV vaccine strain against the background of immunomodulation with the 974zh. It was found that 974zh induces a statistically significant increase in TLR2 gene expression when co-administered with Y. pestis EV at a dose of both 104 CFU and 103 CFU.Conclusion. Y. pestis EV against the background of immunomodulation with 974zh, stimulates the expression of the TLR2 and TLR4 genes, which may indicate an increase in the immunogenic properties of the Y. pestis EV vaccine strain under the influence of this preparation.

Relevance. The new coronavirus infection (COVID-19) is still a public health problem and a threat to socio-economic well-being. Most studies have focused predominantly on humoral immunity, and there are no data on the cellular composition of blood in dynamics. Aim. To study the dynamics of changes in blood cellular composition depending on the type of immunity formed (natural, hybrid, breakthrough, postvaccinal) to SARS-CoV-2 virus. Materials and Methods. A total of 130 volunteers participated in the study. Immunophenotyping of peripheral blood leukocytes using flow cytometry was performed. The presence of specific IgG antibodies to N-protein SARS-CoV-2, total IgA and cytokines (IL-4, IL-10, IFN-γ, TNF-α) was assessed in serum by ELISA. Results and Discussion. A statistically significant increase in BL was recorded in volunteers with hybrid immunity 1 month (14,0% (12,3–16,4%)) after vaccination compared to healthy volunteers (9,1% (6,4–10,2%), p = 0,0007) and people with primary COVID-19 infection (10,2% (8,3–12,1%), p = 0,0134). In volunteers with natural and hybrid immunity, as well as in revaccinated people, an increase in B1-cells (CD3-CD19+CD5+CD27-) was observed during 3–9 months of observation. It is shown that the increase of B-lymphocytes with «switched» class of synthesized antibodies was detected in people with breakthrough immunity. Increased levels of T-lymphocytes expressing HLA-DR were recorded in all individuals during 6–9 months of follow-up. Volunteers with breakthrough immunity showed a significant increase in the positivity index when assessing the presence of specific IgG class antibodies to the coronavirus N-protein compared with volunteers with natural and hybrid immunity. Conclusions. Vaccination promotes protective immunity sufficient for timely activation of memory T- and B-cells in breakthrough immunity and maintenance of immunologic efficacy in hybrid immunity against COVID-19. The results help to assess the strain of innate and adaptive immunity in novel coronavirus infection and to fill gaps in the understanding of immunopathogenesis in COVID-19.

Relevance. COVID-19 is accompanied by high production of cytokines - immune molecules, imbalanced regulation of which leads to disruption of the immune response. Therefore, the study of cytokine status in both vaccinated and re-vaccinated patients is necessary to develop an immunoprophylaxis strategy for COVID-19. Aim. To evaluate the cytokine status in COVID-19 survivors and vaccinated employees of a health care facility against this disease. Materials and Methods. Production levels of cytokines (IL-4, IL-10, IFN-γ and TNF-α) were determined by quantitative enzyme immunoassay in serum of 144 volunteers. Results and discussion. A significant 1.5-fold increase in IL-10 and 2.0-fold increase in TNF-α was found in the group of re-invaccinated overinfected volunteers, and a 2.0-fold decrease in IL-4 compared with the vaccinated group. An inverse correlation between IL-4 and IFN-γ levels and timing after the disease was detected. A significant decrease in IL-4 in survivors (Omicron variant) and an increase in IL-10 in the survivors at the beginning of the pandemic as compared to other re-vaccinees was established. In the vaccinated group, regardless of the vaccine used, IL-10 and TNF-α decreased significantly after revaccination. No statistically significant differences were found between the cytokine status parameters in the survivors before and after vaccination. The predominance of the cellular component of immunity was established in all the examined groups, and the highest proportion of persons with a humoral immune response was detected among the vaccinated volunteers, while the highest proportion of persons with a mixed immune response was detected among the overexperienced non-vaccinated patients. Conclusions. The results obtained supplement the available data on coronavirus infection and indicate the need for further research.

Background. There are many aspects of the development of immunity to the SARSCoV-2 virus, that remain poorly understood, like the influence of age-related characteristics on the intensity of immunity and the course of the disease. Studies of the state of immunity are widely used, mainly in the adults. But questions of the patho- and immunogenesis in children remain unsolved. Determining the nature of seroconversion of antibodies to SARS-CoV-2 in this age group is important information for serological monitoring for targeted immunoprophylaxis of the population and forecasting the epidemic situation in the region.The aim. Evaluation of the dynamics of seroprevalence of specific antibodies to SARS-CoV-2 in children of the Irkutsk region during the pandemic of a new coronavirus infection.Materials and methods. Study was conducted among the child population of the Irkutsk region in the period June 2020 – December 2021 as part of the Rospotrebnadzor project to assess population immunity to SARS-CoV-2 in the population of the Russian Federation. The content of antibodies to SARS-CoV-2 was determined by ELISA using native commercial test systems.Results. Population immunity among the child population of the Irkutsk region was characterized by an upward trend from 7.8 % at stage 1 to 98.4 % at stage 6 of the study. IgG to SARS-CoV-2 remained in 72.8 % and formed in 25.6 % of previously seronegative children. Antibodies were detected in 66.1 % of cases and persisted for up to 10–15 months after COVID-19 infection. The proportion of asymptomatic forms of infection among seropositive volunteers was 69.5 %, which determines the high intensity of the latent epidemic process.Conclusion. The level of seroprevalence was 98.4%. The current results of serological monitoring serve as a scientific basis for adjusting the list and scope of management decisions on the organization of preventive anti-epidemic measures, including vaccination.

Relevance. To date, the specific prevention of plague remains the most effective measure to prevent to prevent the deterioration of the epidemiological situation for this especially dangerous infection in the territory of the Russian Federation. The development of new vaccine preparations created on the basis of avirulent strains of Yersinia pestis with specific genetic defects, can play a crucial importance in the issues of plague immunoprophylaxis.Aim. Determination and comparative analysis of the genomic organization of avirulent strains Y. pestis I-1, Y. pestis I-3536 and vaccine strain Y. pestis EV line NIIEG.Materials and methods. The features of the genetic structure of three Y. pestis strains were studied using plasmid screening and whole genome sequencing.Results and discussion. It was found that the Y. pestis I-1 and Y. pestis I-3536 strains, like Y. pestis EV, lack the chromosomal pgm region. Analysis the genome sequence of Y. pestis I-1 showed that this strain is devoid of the plasmid pMT1, while its individual genes were found in the chromosome structure and the unique 340 kb plasmid. It was revealed that the Y. pestis strain I-3536 lost the plasmid pCD1, however, fragments homologous to this plasmid were found in the structure of its genome.Conclusion. The data obtained allow us to recommend Y. pestis I-1 and Y. pestis I-3536 as the basis for the development of a modern live attenuated plague vaccine.

Introduction. An urgent direction is the search for means that increase the effectiveness of the Y. pestis EV NIIEG vaccine and reduce the side pathological manifestations caused by it. Organoselenium compounds have immunotropic properties and increase the antioxidant potential of the body, as well as have an antidystrophic effect and an antiallergic effect. Materials of the study of the immunomodulating effect of the experimental selenium-containing compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the macroorganism of laboratory animals are presented.The aim. To evaluate the effect of the organoselenium compound 974zh on the structural rearrangement of the organs of experimental animals in the dynamics of the vaccine process caused by Y. pestis EV.Methods. The study was carried out on 70 certified outbred white mice. Histological material (thymus, lymph nodes, spleen, adrenal glands, liver) was embedded in paraffin, semi-thin sections were stained with hematoxylin and eosin, thionin, and by the Brachet method. The severity of pathological changes in the liver and adrenal glands, proliferation of plasma cells and structural changes in immunocompetent organs (thymus, lymph nodes and spleen) were assessed. Microphotography and quantitative analysis were performed using MoticImagesPlus 2.0. Statistical processing was carried out using the computer program Statistica.Results. It has been established that the combined administration of 974zh and Y. pestis EV leads to morphological and functional restructuring of immunocompetent organs, enhances the proliferation of plasma cells in the spleen and lymph nodes, and eliminates negative changes in the liver and adrenal glands. Conclusion. Thus, the 974zh preparation enhances the immunogenic effect of the Y. pestis EV vaccine strain, increasing the T- and B-dependent zones of the spleen and lymph nodes, increasing the proliferation of plasma cells, and also significantly reduces pathological changes in the liver and adrenal glands.

Relevance. In Russia, the live plague vaccine (LPV) is used for specific prophylaxis of plague. Immunological monitoring of humans vaccinated by LPV in order to search for informative diagnostic markers, as well as to improve the tactics of epidemiological surveillance of plague enzootic territories is an urgent area of research.The aim is to assess the parameters of cellular and humoral immunity in humans revaccinated by LPV who permanently reside on territory of the Tuvinian natural plague focus.Materials and methods. The study involved 76 volunteers from the Republic of Tuva, revaccinated by LPV. Blood sampling was performed before vaccination and 1, 3, and 6 months after revaccination. The study included the determination of cytokine production (IFN-γ, IL-4, TNF-α), specific antibodies, immunoglobulins (IgM, IgG, IgA and IgE) and lymphocyte subpopulation composition (CD3, CD4, CD8, CD16, CD19, immunoregulatory index).Results. A decrease in IgG and IgM and an increase in IgA were found after vaccination with LPV and their increase after revaccination. Correlation relationships were revealed between immunoglobulins, B cells and IL-4. Revaccination leads to an increase seroconversion. The activation of humoral immunity in humans vaccinated against plague is also evidenced by dynamics of changes in the subpopulation composition: an increase in B-lymphocytes and natural killer cells, a decrease in T-helpers and immunoregulatory index, and cellular immunity stimulation is an increase in spontaneous and induced production of pro- and anti-inflammatory cytokines.Conclusion. It has been shown that LPV is capable of causing the body’s immune restructuring and activating the cellular and humoral mechanisms of immunological protection. For a complete understanding of the development and preservation of antiplague immunity, it is necessary to continue the annual immunological monitoring of the population living on the territory of the Tuvinian natural plague focus, using additional modern research methods.

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.

This review article analyzes the data on the role of selenium in the regulation of the metabolic and immune status of a macroorganism. The data on endogenousfunctional selenium-containing molecules, which include selenocysteine, selenomethionine, and selenoproteins, are considered. The data on the pathologies associated with the deficiency of this microelement, its immunotropic properties and adjuvant effects are presented. The role of selenoproteins in the regulation of redox processes has been shown. The data on the immunotropic activity of compounds containing selenium and the prospects for their use as adjuvants are analyzed. The last section is devoted to the analysis of literature data on the biological properties of synthetic selenium compounds with an activity that mimics the catalytic activity of selenoproteins. The analysis of the data on the functional activity of selenoproteins carried out in this work indicates their key role in the regulation of metabolic and immune processes, as well as in maintaining homeostasis. The information presented in this review on the biological activity and mechanisms of action of new synthetic low-toxic organic compounds of selenium can serve as a basis for the development of nonspecific means of metabolic and immune correction of vaccinal processes caused by both live attenuated vaccines and artificially created ones.

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.

Objective of the seroepidemiological study was to determine the level and structure of herd immunity to SARS-CoV-2 among the population of the Irkutsk Region during the period of an increase in the incidence of COVID-19.Materials and methods. The content of antibodies to SARS-CoV-2 was determined by ELISA applying a reagent panel “ELISA anti-SARS-Cov-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk).Results and discussion. The investigation has revealed that the herd immunity of the total population of Irkutsk Region amounted to 5.8 %. The greatest share of seropositive persons was among the children aged 14–17 (13.8 %) and 1–6 (11.8 %). It has been established that the risk of infection increases by 3.1 times in case of contact with COVID-19 patients. After exposure to COVID-19, antibodies were produced in 56.5 % of the cases. The share of asymptomatic forms among seropositive residents of the Irkutsk Region reached 81.2 %. Consequently, during the chosen period of increased COVID-19 incidence among the population of Irkutsk Region low level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterize high intensity of the latently developing epidemic process. The results obtained can be used when organizing preventive measures, including vaccination, and for forecasting morbidity rates.

Background. Bacillus anthracis is a microorganism that causes anthrax. Because of irrational therapy, this particularly dangerous infectious disease leads to a systemic spread of bacteria in the body through histohematological barriers. Bacilli entering the brain subsequently lead to hemorrhagic meningitis. Despite intensive antibiotic therapy, that kind of meningitis is difficult to cure and therefore highly lethal. Studying characteristics of anthrax’s isolates of different origin and genotype is an actual area of research.The aim of the study is searching for pathomorphological and histological changes in the brain regions of experimental animals with anthrax infection, caused by B. anthracis with different plasmid spectrum.Materials and methods: The study was conducted on 200 certified white mice, three B. anthracis strains were used as research objects: B. anthracis I-323 (рХО1– /рХО2– ), B. anthracis I-275 (рХО1- /рХО2- ), and B. anthracis I-217 (рХО1+ / рХО2– ). The material for histological examination was the brain of mice, embedded in paraffin, and then sections were prepared using a microtome and stained with hematoxylin-eosin and Nissl toluidine blue. The degree of neuronal damage was assessed by calculating the semi-quantitative factor and determining the average size of the neuron nuclei, and the numerical density of cells in 1mm2 was studied. Microphotography and quantitative analysis was performed using the Motic Images Plus 2.0 application package. Statistical processing of the results was performed using the program “Statistica 6.0”.The results of the study showed that the brain of infected mice shows signs of hemorrhagic leptomeningitis, the manifestations of which are more pronounced in mice infected with weakly virulent plasmid strains of B. anthracis and fallen mice.Conclusion. Multicomponent exotoxin and specialized proteins, encoded in the pathogenicity plasmid of microorganisms, allow B. anthracis to easily overcome histohematological barriers and cause severe septic anthrax. The results obtained during the study supplement the available information on the pathogenesis of anthrax and indicate the need for further research in this direction.

Background. Detection of the pathogenicity factors is one of the actual directions in studying of the anthrax causative agent. First of all, it includes the presence of tripartite toxin, capsule and the related structural and regulatory genes. Their presence or absence is defined by structural changes in cellular structure of blood and immunocomplex organs of a macroorganism.Objective: To conduct a comparative analysis of subpopulational structure of marrow and peripheral blood cells at anthrax infection in experimental animals and to trace dynamics of the infectious process caused by Bacillus anthracis of different genotypes.Methods. Comparative examination of subpopulational structure of red marrow and peripheral blood cells of white mice in dynamics of the infectious process caused by B. anthracis of different genotypes was conducted. Also, neutrophil maturing index and leucoerythrocytic correlation were calculated in red marrow. Degree of manifestation of neutrophil pathological granularity was revealed in peripheral blood smears stained by the Freifeld’s method. Statistical processing of the received data was conducted using the computer program “Statistics”, version 6 (Novosibirsk). Authentic results were considered if the error probability was less than 0.05 (р < 0.05) in relation to the control.Results. It is revealed that alterations in white mice infected by B. anthracis strains with the same set of plasmids are significantly various.Conclusion. The resulted data permit to assume that the distinction of pathological alterations in peripheral blood and red marrow is probably connected with the other factors of the pathogen invasiveness like enzymatic activity, ability to adhesion and many others.

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

Currently, one of the topical areas of research is the development of new antigen preparations for the specific diagnosis and prevention of brucellosis, since indication of the pathogen and prevention of the disease is complicated by the ability of brucella to dissociate, and live vaccines used for specific prevention of brucellosis have residual virulence. Thermal extracts (TE) obtained from Brucella abortus I-206 in the L- and S-form can be used as such promising antigens. It is known that TE in the L- and S-forms have immunogenic properties, as well as a modulating effect on the proliferation of immunocompetent cells, morphological changes in the immunocompetent organs of experimental animals.The aimof the work is to study the effect of Brucella abortus thermal extracts in L- and S-forms on the functional state of the cells of experimental animals.Materials and methods. The study was performed on 100 certified white mice. As objects of study, we used the B. abortus I-206 TE in L- and S-forms. Evaluation of the effect of antigenic drugs on the functional state of phagocytes of laboratory animals in vitro was performed on peritoneal macrophages. The total activity of the respiratory chain enzymes in the NBT-test and superoxide dismutase was determined. Cells of intact animals served as controls. As a positive control, a commercial antigenic LPS preparation Escherichia coli was used. The content of cyclic nucleotides in homogenates of immunocompetent organs was determined using ELISA.Results.This study presents materials on the study of the effect of TE on the bactericidal activity of phagocytes and the level of cyclic nucleotides in immunocompetent organs. It has been established that TEs activate oxygen-dependent bactericidal systems of phagocytes. When studying the effect of TE on the content of cyclic nucleotides in immunocompetent organs of white mice, an increase in their concentration was revealed, indicating an increase in the functional activity of the cells.Conclusion.The obtained data make it possible to substantiate the need for a further detailed study of the immunogenic properties of B. abortus TE in the L- or S-form on the organism of experimental animals.

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. Brucellosis is an acute infectious-allergic zoonotic disease in which sick farm animals are the main source of infection for humans. Immunization of animals and people on the territory of Russia is carried out by live vaccines, which, having a high immunogenicity, can cause clinical, hematological and immune changes. Therefore, the work on the design of new vaccines that provide high protection and do not possess reactogenicity, agglutinogenic and sensitizing activity is the current direction of the study. Methodology. The study was performed on 72 outbred white mice immunized with inactivated B. abortus 19 ВA vaccine and thermal extracts (TE) of B. abortus I-206 in L- and S-form. Morphofunctional changes in the regional lymph node, spleen, and thymus of experimental animals were examined on days 3, 7, 14, and 21 of the time of immunization. Results.The influence of single introductions thermoextracts B. abortus I-206 in L-and S-form in comparison with inactivated vaccine B. abortus 19 ВА. the removal or the morphohistologic indices of immune organs of experimental animals. Found that thermoextracts have the ability to activate immune adjustment within the structures of the spleen and lymph nodes, without causing side effects, including allergic reactions. Conclusions. Preparations obtained from B. abortus in the L- and S-forms have the ability to activate immunological rearrangement in immunocompetent organs without causing any side effects. The results indicate the promise of further research in this direction.

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.

The creation of immuno-biological drugs to increase the effectiveness of specific immunotherapy and immunoprophylaxis is a current trend in medicine to date. Therefore, the search and development of new safe and effective artificial bioorganic complexes (immunomodulators) capable of stimulating individual responses of immune system to reduce infectious morbidity is an important area of research. At the moment, such promising preparations can be considered water-soluble polymeric materials and organo-inorganic polymer nanocomposites with nanoparticles of various metals which possess immunomodulating and bactericidal properties. The study results of the effects of 1-vinyl-1,2,4-triazole copolymer with N-vinylpyrrolidone and nanocomposites based on it with gold and silver nanoparticles on acute toxicity and functional state of immunophagocytic cells of experimental animals, as well as the production of IFN-γ, TNF-α and IL-4 by human blood lymphocytes are represented in this article. It was established that the tested preparations do not cause increase in body temperature, decrease in mass and death of animals. It was shown that they also have the multidirectional action on cytokine production by human blood cells in vitro, the ability to increase activity of оxidative stress-related enzymes and antioxidant protection of phagocytes. The data obtained by us allow to explain the need for further investigation of the actions of nanocomposites and copolymer in vitro and in vivo.

The article covers the issues related to the scientific substantiation and methodological support of immunological monitoring of persons vaccinated against plague upon epidemic indications. The problematic issues of the methodology for the assessment of immunological efficiency (efficacy) of plague live vaccine (PLV) are noted. The current tasks and possible prospects for the introduction of immunological monitoring of persons vaccinated against plague upon epidemic indications have been defined. The algorithm of efficacy estimation of plague live vaccine in vaccinated (revaccinated) persons has been tested under real conditions. Analysis of the results of efficacy evaluation of plague live vaccine among vaccinated (revaccinated) people against plague living in the territories of natural foci of this infection has been performed. Demonstrated is the possibility of using immunological monitoring results in creating an objective basis for improving the strategy of specific plague prevention in natural foci of this infection. The priority areas for further optimization of the specific plague prevention in the territories of natural foci of the infection, including those related to the formation of individual regimen revaccination tactics, taking into account the possibilities of creating modern and effective vaccines, are outlined.

Live vaccines are used for specific brucellosis prophylaxis in the Russian Federation. These vaccines in addition to a number of positive properties have some limitations including high agglutinogenicity, reactogenicity, sensitizing activity. In this connection, the development of subunit vaccines without adverse reactions is a perspective direction in modern vaccinology. Complex morphological research of the adrenal glands and comparative analysis of peripheral blood (leukogram, leukocytic index and index of allergization) of white mice immunized with thermoextracts (ТE) of Brucella abortus I-206 in L- and S-form and inactivated vaccine B. abortus 19 ВА were conducted. It was shown that ТE unlike B. abortus 19 ВА caused minor alterations in peripheral blood of the experimental animals in early periods of observation (increase of allergization index, changes in leukogram) with the subsequent levelling to the values in control. Expositions of the adrenal gland zoning were determined and cellular structure was estimated in consideration of morphometry. Changes in architectonics of the mice organ immunized with B. abortus 19 ВА were revealed. These alterations could indicate the stress-reaction development. In case of ТE application the given changes were insignificant and were developed in early periods. The revealed morphological changes in adrenal glands of laboratory animals permit to prove the necessity of realization the further experimental researches to ТE application as the components for development of a subcellular brucellosis vaccine.

Immunogenic properties of cell wall (CW) preparations of Francisella tularensis four subspecies are investigated. It is shown that the preparations from F. tularensis urea lysates are not toxic for experimental animals. Besides, CW of F. tularensis А-61 subsp. mediasiatica and F. tularensis B-399 A-Cole subsp. tularensis possess immunogenic activity in experimental tularemia caused by F. tularensis 306 subsp. holarctica.

The evaluation of sensitization conducted on guinea pig leukocytes immunized with the cell wall preparations of F. tularensis. In this research was shown that the cell wall preparations F tularensis subsp mediaasiatica A-61 and F tularensis subsp tularensis В-399 A-Cole do not caused allergization in contrast with cell wall prepararions of F. tularensis 15 (extracted by Research Institute of Epidemiology and Hygiene) and F. tularensis subsp. holarctica 306.

At present, development of effective vaccines of new generation is an actual problem, in particular concerning the tularemia causative agent. It determines the need to search antigen determinants with high immunogenic activity. Some authors demonstrate that outer membrane proteins of Francisella tularensis possess immunological activity. This fact gave occasion to isolation and comprehensive study of F tularensis cellular envelopes as a perspective component in vaccine engineering. The influence of cell walls of F. tularensis was studied for morphological changes in immunocompetent organs of experimental animals. Cell walls were obtained from three virulence strains of living cultures: F. tularensis subsp. mediaasiatica А-61, F. tularensis subsp. nearctica В-399 A-Cole, F. tularensis subsp. holarctica 306 and vaccine strain F. tularensis subsp. holarctica 15 (extracted by Research Institute of Epidemiology and Hygiene). Cell walls of different subspecies of F. tularensis stimulate the production of antibody forming cells and cell proliferation more in T-dependent zones of lymph nodes and spleen. It has been determined that these antigen preparations do not cause stress reaction of the experimental animal organisms. Basing on the findings, we made a conclusion that there is a need for further detailed investigation of immunogenic properties of CE F. tularensis subsp. holarctica 306, F. tularensis subsp. mediasiatica А-61 and F. tularensis subsp. tularensis B-399 A-Cole as perspective components in development of tularemia vaccines.

Dynamics of acidic and alkaline phosphatase activities was examined in thymus and spleen of laboratory mice immunized by cell wall preparations of Francisella tularensis of different subspecies. Cell wall preparations of two subspecies: F. tularensis subsp. mediaasiatica А-61(385) and F. tularensis subsp. novicida В-399 A-Cole (386) stimulated the rise of acidic and alkaline phosphatase activities in earlier time (7 days) after immunization than the others. It was correlated with their protective activity. On the basis of the results it is concluded that the studying of the acidic and alkaline phosphatase activities in immunocompetent organs can serve as one of the criteria for evaluation of efficiency of immunobiological preparations.

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.

Data of histological study of pathomorphological changes in liver of white mice with experimental plague are represented in the article. An important element in evaluation and prediction of the pathological process in the liver is the analysis of hepatocyte karyokinesis, the mitotic index calculation, the counting number of atypical mitosis and the degree of organ regeneration ability. Dynamics of these liver changes at infection process in experimental animals caused by Yersinia pestis plasmid variants was investigated in this work. The variability of liver injuries was shown depending on plasmid-associated virulence of the infection agent. It was proved that the Y. pestis strain carrying three basic pYP (6 mDa), pYV (45 mDa), pYT (61 mDa) plasmids caused the most severe systemic disease with lethal outcome as a rule. Lack of species-specific plasmids and especially virulence and pathogenicity plasmids reduced the rate of infection process generalization and the ability of the pathogen to initiate pathological changes incompatible with the microorganism life. Therefore, all morphological liver changes in experimental plague infection are directly dependent on plasmid profile of the pathogen. The mechanism of toxicity included the damaging effect of the toxin to the cellular structures and failure of the metabolic processes in the organism. Acuity of intoxication and the development of pathological process can be estimated by exploring changes in liver morphology.

The current state of the problem of Brucella interactions with the host in the review is discussesed. Provides information about the mechanisms of persistence of Brucella in the host organism due to their ability long remain in the cells immunoregulatory system. Data on the differences of Brucella in smooth and rough forms on invasive ability are presented. The key role of the macrophage in Brucella infection is shown. Promising areas of research in the field of immunobiology of brucellosis are indicated.

Objective of the study is to sum-up the results of prophylactic (anti-epidemic) measures associated with elimination of epidemic focus in Kosh-Agach Region of the Republic of Altai in 2016. Materials and methods. Utilized were the data of reporting and source documentation from Altai Plague Control Station, Rospotrebnadzor Administration in the Republic of Altai, RusRAPI “Microbe”, and Irkutsk RAPI. Results and conclusions. It is pointed out that carried out in 2016 complex of organizational, anti-epidemic, and sanitary-prophylactic activities against plague is the importnant stage of rehabilitation of Gorno-Altai high-mountain natural plague focus, the final goal of which is maximally possible decrement of risks of primary human infection with plague, and in case of occurrence of such – performing of prompt response measures on localization and elimination of epidemic focus. It has been substantiated that for epidemic risk minimization in 2017 it is necessary to continue prophylactic vaccination, desinsection and deratization in the areas of predictive epizootic situation aggravation, which is contained in “Complex Action Plan of the Rospotrebnadzor Institutions for Sanitation and Rehabilitation of Gorno-Altai high-mountain natural plague focus in Kosh-Agach Region of the Altai Republic in 2017”. It is also necessary to provide for implementation of the Program on lowering risks of importation from cross-border Sailyugemsky natural focus and spread of plague in the territory of the Russian Federation, within the frames of RF Government Order No 1864-p, dated 05.09.2016.

Experimental data concerning complex study of antioxidant activity of Y. pestis with different plasmid spectrum (wild-type Yersinia pestis subsp. pestis, Yersinia pestis subsp. altaica and their isogenic variants) are represented in the article. Superoxide dismutase activity of the tested Y. pestis strains was from 6.0 to 9.0 x 109 microbe cells. Significant differences between the Y. pestis strains with different plasmid composition were not detected by this parameter. Our results, consistent with the data of other authors, tell that superoxide dismutase activity is a thermo-inducible feature and does not depend on a plasmid spectrum. High peroxide destroying activity was also detected in all tested Y. pestis strains. The differences between the strains regarding their common peroxide destroying activity were found. This parameter of the plague microbe strains lacking pYP plasmid was at least 3 times lower than common peroxide destroying activity in strains with this plasmid in the genome. In our opinion these revealed differences were caused by characteristics of plasmid spectrum. The common peroxide destroying activity's degree of Y. pestis strains can be associated with the presence of pYP plasmid in the genome. The isogenic variants of Y. pestis strains lacking one of the plasmids had smaller pathogenic activity. This fact points to the need for further study of these strains.

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.

Relevance. In the Russian Federation is noted the negative dynamics of epizootic process of brucellosis among epidemiologically important species of farm animals (cattle and small ruminants), which represents a threat to the population. Used in Russia live vaccine based on a strain of Brucella abortus 19 the BA has reduced virulence, but capable at high doses (108 -2 109 m.c.) cause a generalized infection in guinea pigs and humans, and in violation of the rules cause post-vaccination complications. Goal. Assess possibility of the thermo-extract derived from the S- and L-forms of Brucella, get an immune response in guinea pigs, and reduce the risk of infection with virulent brucella. Materials and methods. Two series of experiments were carried out on guinea pigs. Immunized guinea pigs thermo-extracts (TE) from a strain of B. abortus I-206 in the S- and L-forms, and live brucellosis vaccine (Scientific and Production Association for Immunological Preparations «Microgen», Russia). To infect guinea pigs using virulent B. abortus 544 (Reference) and B. melitensis I-203 from the museum of living cultures of the Irkutsk Scientific Research Anti-Plague Institute. Results. In the first and second experiment after immunization L TE in dose 5 mg and 10 mg after infection with B. abortus and B. melitensis 5441-203 were approximately similar results. Immunization of Brucella in TE S-form or complex of L + S TE either of two doses (5 mg or 10 mg) cultures after infection B. abortus and B. melitensis 5441-203 gave the same result as a vaccine B. abortus 19VA. Conclusions. The results indicate the prospects of further study of experimental steps for using immunizing agents TE S, L TE and TE S + L on the laboratory animals.

The paper presents data on changes in the respiratory part of lungs of white mice with experimental plague caused by Yersinia рestis strains with different plasmid composition of Tuva and Gorno-Altaisk natural foci of plague and breeding clones. Morphological and structural changes in the lungs, which appear different degree of activation of the immune response and the severity of the pathological process caused by Y. pestis subsp. altaica and Y. pestis subsp. pestis and their isogenic plasmid options.

The article presents the research results of the non-specific immune factors of guinea pigs immunized the antigenic preparation strain Bacillus anthracis Sternе 34F2 per se and combinated with cobaltarabinogalactan and argentogalactomannan. It is established that antigenic preparation and nanocomposites can stimulate oxygen- and nitric oxygen-dependent bactericidal systems of the experimental animal phagocytes and they can be used to construction of a chemical vaccine against anthrax.

The article presents the research results of immunogenic potency of antigen preparation Bacillus anthracis Sterne 34F on the guinea pig model. It was found that a single inoculation of this preparation, before the contamination of virulent B. anthracis strain, protects 60-80 % of experimental animals. The metal-containing nanocomposites were used to improve the immunogenicity of this antigen preparation. The combined use of antigenic preparation S-2 with argentogalactomannan increases its immunogenic potency and conduces to the survival of experimental animals. Argentogalactomannan exhibits adjuvant properties enhanced the immunogenic features of the S-2 B. anthracis 34F2 Sterne that may indicate its availability as an adjuvant in the construction of chemical vaccines.

Study of Bacillus anthracis 34F2 Sterne antigenic preparation S-2 and its combined use with nanostructured cobalt-arabinogalaktan (Со-АG) is presented. The ability of these preparations to stimulate proliferation and differentiation of B-lymphocytes is demonstrated. However, content of the B-lymphocyte circulating subpopulations depends on the time of observation. Co-AG exhibits adjuvant properties enhanced the immunogenic features of the S-2 B. anthracis 34F2 Sterne that may indicate its availability as an adjuvant in the construction of chemical vaccines.

We have estimated the effects of the Brucella abortus 19 ВА inactivated vaccine, thermo extracts of Brucella abortus I-206 in the L- and S-forms and corpuscular antigen of Brucella abortus I-206 in L-form on the population and subpopulation structure of blood cells and peritoneal fluid of white mice. It was showed that the antigen preparations of Brucella abortus I-206 in L-form didn't caused endogenous intoxication of the organism of experimental animals in distinction from the inactivated vaccine of Brucella abortus 19 BA.

Data of the proteolytic and superoxide dismutase activities of Yersinia pestis strains with different plasmid spectrum are presented. It was established that superoxide dismutase activity of the tested Y. pestis strains was not associated with its plasmid composition. Some differences were revealed concerning the proteolytic activity. Direct dependence of proteolytic activity level of the studied Y. pestis strains on pYV plasmid presence in its genome was found.

The article presents the results of the research of effect of metal-containing nanocomposites on the content of splenic Band T-lymphocytes of white mice. Phenotypic analysis of the spleen cells suspension was conducted by flow cytometry on BD FACSCanto ™ П. Stimulating effect of these medications on the immune response formation is showed and is proved by the increase of content of B-lymphocytes and T-helper cells and it indicates cooperative interactions between the cells of immune system. It was experimentally showed that the medications 2-N-HTP-Ag, GM-Ag can be recommended for the further research in order to increase protective properties of an organism.

The article presents the data on the influence of Yersinia pestis plasmid profile on subpopulation structure of mononuclear cells of peritoneal fluid of mice at the early stages of infectious process. It was showed that change of cellular composition of peritoneal fluid of the experimental animals depended on the plasmid profile of Yersinia pestis strains. The phase character in the changes of quantitative composition of the mast cells of peritoneal fluid of white mice infected with Y. pestis strains with different plasmid spectrum was determined.

Data of Yersinia pestis plasmid structure influence on its adhesive properties and phagocytic activity of peritoneal macrophages in vitro are represented. It is shown that Y. pestis strains of diverse subspecies differing by a plasmid profile, particularly by one of the plasmids (pYP, pYV) lacking, possess low adhesive activity and promote the increase of laboratory animal phagocyte absorbing capacity.

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.

The modern findings of scientific research in a live plague vaccine range such as production antibiotic-resistant subcultures of the vaccine strains, design of the low-development of reaction producers vaccine strains, production of oral (tablet) preparation are represented in the review. Some techniques of production improvement live plague vaccine are formulated: stabilization of a number alive microbial cells in a inoculation dose of a license vaccine by decreasing of cultivation temperature mode from 27 °C till 21°С, concentration of microbial cells in ampoule from (5-10) × 1010 till (1-4) × 1010 per 1 ml, reduction freezing-drying step from 28 till 18 h, decreasing of amount dose in ampoule from 100-125 till 20-50 and furthermore acceleration of production process of microbial cells concentrate (fermentation in the bioreactor, tangential microfiltration) and formulation combined (meat-soya nutritious base) medium and conditions of their preparation (time reduction enzymatic hydrolysis from 14 till 3 days). The tendenceis of refinement of a technological process of equipment link were researched, such as using bioreactors instead of apparatusfor a cultivation microbesShesterenko, disposable bags Flexboy, which are allowed to eliminate the application of glass bottles and operation of a bottle assembling, also using of robotizing sublimation installations for drying of a liquid form of live plague vaccine, which are allowed to exclude utilization of low-temperature refrigerators. Beside of regulating estimation method of immunogenicity (calculation of effective immunizing dose) and quantitative account of a phenomenon of survival white mice the cyto-enzymochemical and morphometric rates are suggested to estimate the quality of ultimate product live plague dry vaccine, changes of those are charactering immunologic activity and state of mobilizing and bactericidal abilities of a organism phagocyte system cells.

We studied influence of silver-containing nanocomposites — galactomannan and poly-1-vinyl-1,2,4-triazole — on cell structure of peripheral blood and red marrow of white mice. The results obtained after the experiments testify that these nanocomposites aren't toxic, the changes caused by their introduction are productive and. part of them points at the activization of immune system of macroorganizm.

Modern data concerning functional regularities of the secondary signal systems of cyclic nucleotides (CN) in immune and. pathological reactions of a macroorganism, are analyzed, in this review. Intracellular regulatory mechanisms controlling CN system, and. its interaction with other signal systems are described. Influence of endogenic and. exogenic factors on activity of CN system, components and. its use as means or «targets» of special exposure to immune and. pathological reactions of a macroorganism, are examined.