Prospects for the use of synthetic organoselenium compounds for the correction of metabolic and immune status during vaccination with live attenuated vaccines against especially dangerous infections

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

Assessment of indicators of specific humoral immune against COVID-19 in children during the distribution of a new coronavirus infection in the Irkutsk region (2020–2021)

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

Prospects for the Use of Thermal Extracts of Brucella abortusI-206 in S-and L-Forms in the Diagnosis and Prevention of Brucellosis

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

Structural rearrangement of organs of white mice vaccinated with Yersinia pestis EV in combination with organoselenium compound 974zh

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

ACTION OF 1-VINYL-1,2,4-TRIAZOLE COPOLYMER WITH N-VINYLPIROLIDONE AND METAL-CONTAINING NANOCOMPOSITES ON FUNCTIONAL STATE OF PHAGOCYTIC CELLS

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

Assessment of Toxic and Immunoadjuvant Properties of Nanocomposites

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

Changes in the Organs of Experimental Animals in the Dynamics of the Infectious Process Caused by <i>Bacillus Anthracis</i> with Different Plasmid Profiles

Background. The current direction is the study of anatomical and histological changes caused by the causative agent of anthrax with a different plasmid profile. It was found that Bacillus anthracis strains with the same set of plasmids and the same morphological, serological and cultural properties sometimes have different pathogenicity.Aim of the study. Comparative analysis of anatomical and histological changes in the organs of experimental animals in the dynamics of the infectious process caused by the pathogen B. anthracis with different genotypes.Methods. Four strains were used as the study object: B. anthracis I-275 (pCO1–/ pCO2–), B. anthracis I-323 (pCO1–/ pCO2–), B. anthracis I-217 (pCO1+/pCO2– and B. anthracis 34F Stern pCO1+/pCO2–). The study was conducted on 260 certified white mice. Histological material was embedded in paraffin, semi-thin sections were stained with hematoxylin-eosin, thionine, and according to Brachet. The severity of pathological changes, the presence of the pathogen, and the proliferation of plasma cells were evaluated. The changes detected during the autopsy of the animal and the results obtained during the histological examination of the anatomical material were analyzed and generalized. Microphotography and quantitative analysis of plasma cells were performed using the “Motic Images Plus 2.0” application software package. Statistical processing of the obtained data was performed using the computer program “Statistics”, version 6 (Novosibirsk). The results were considered reliable if the probability of error was less than 0.05 (p &lt; 0.05) in relation to the control.Results. Differences in anatomical and histological changes in organs and tissues of white mice infected with B. anthracis with the same set of plasmids were revealed. It was found that in animals infected with non-plasmid strains of B. anthracis, the proliferation of plasma cells is significantly reduced compared to animals infected with singleplasmid strains of the anthrax pathogen.Conclusion. The obtained data suggest that the revealed differences are related to the plasmid profile of the studied strains, but also to the peculiarities of their enzymatic activity, adhesion ability, and other factors. Thus, anthrax strains that have the same morphological, serological and cultural properties sometimes have different virulence. And also, anthrax strains that have lost virulence lose their immunogenicity, as evidenced by the ratio of plasma cells

Population immunity to SARS-CoV-2 virus in residents of the Irkutsk Region in the dynamics of the epidemic

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

Studying Humoral Immune Response at Mild and Asymptomatic COVID-19 Forms

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

Efficiency of Human Plague Vaccination in Tuvinian Natural Plague Focus

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