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Advanced molecular-genetic methods for the diagnosis and typing of Yersinia pestis ssp. pestis in the field and clinical material are used for epidemiological surveillance of plague in the Saylyugem natural focus. The aim of the work was to study the spatial genotypic structure of Y. pestis ssp. pestis in the transboundary Saylyugem natural plague focus using MLVA25 typing. Materials and methods. The MLVA25 typing of 160 strains of Y. pestis ssp. Pestis isolated in the Saylyugem natural plague focus in 2012–2021 was carried out. Phylogenetic tree construction was performed with the help of UPGMA and MST methods. Results and discussion. The Y. pestis ssp. pestis strains isolated from the Saylyugem natural plague focus were differentiated into 15 MLVA types by the 25 VNTR loci cluster analysis. The studied strains form a homogeneous complex of MLVA25 types without marked geographical distribution across seven spatial groups. The analysis of the frequency of occurrence of the tandem repeats number for three variable loci of Y. pestis ssp. pestis strains shows the significant differences between the samples from the Mongolian and Russian parts of the Saylyugem natural plague focus. The most pronounced differences in spatial genotypic structure are traced through the yp4280ms62 locus.

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.

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 < 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.

Objective: investigation of phylogenetic origin and affinity of Yersinia pestis strains isolated from field material collected during the epizootiologic survey of the Mongolian part of trans-boundary Sailyugem natural plague focus. Materials and methods: MLVA25-typing of 81 Y. pestis strains, including 55 isolates from the Mongolian part of transboundary Sailyugem natural plague focus, collected in 2017-2018 was carried out. The plague agent strains isolated in different years in the natural foci of Northwest Mongolia and Southern Siberia were used as comparison group. Whole genome sequencing was performed for 21 Y. pestis strains subspecies pestis isolated in Mongolia in 2018 and 1988-1990 and in Gorny Altai of the Russian Federation in 2012-2016. SNP-typing was conducted on the basis of whole genomes of Y. pestis strains identified in the current research and also genomes from GenBank international database. Search of single nucleotide polymorphisms in Y. pestis genomes was carried out in two ways: by means of snippy v. 4.3.5 software and using mummer v. 3.1 package and a set of the author’s scripts. Phylogenetic reconstruction was conducted with the help of RAxML method. Results and discussion: Results of MLVA25 typing of Y. pestis subsp. pestis demonstrated that the strains isolated in Mongolian and Russian parts of the Sailyugem and Khuukh-Serkh-Munkh-Khairkhan natural foci belong to one common cluster. SNP-typing placed the studied isolates from the Mongolian and Russian territories into 4. ANT phylogenetic line with high level of reliability which testifies to the genetic similarity of the specified pathogen groups. The data of MLVA- and SNP-typing showed insignificant variability of the plague agent in the territory of the Mongolian part of trans-boundary Sailyugem natural plague focus. On the basis of the conducted research and results of epizootiological monitoring of Russia and Mongolia border territories it is possible to draw a conclusion on gradual wide penetration of Y. pestis subsp. pestis mainly into grey marmot settlements in Southeast Altai from Northwest Mongolia.

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.

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.

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.

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.

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.

Objective of the study was a complex pheno- and genotypic investigation of Yersinia pestis I-3595 and Y. pestis I-3596 strains, isolated from marmots that were the source of human infection in 2015. Materials and methods. A comprehensive microbiological, molecular-genetic and mass-spectrometric studying of Y. pestis ssp. pestis strains, isolated from two grey marmots that became a cause of the plague case in Gorno-Altai high-mountain focus in 2015, was performed using up-to-date methods. Results and conclusions. It was established that the studied Y. pestis strains belonged to the main subspecies. Results of plasmid screening, multilocus VNTR-and mass-spectrometric analyses showed that those strains were closely related to Y. pestis variant detected in the focus in 2012 and in 2014, and circulating in Northwest Mongolia and Tuva natural focus.

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.

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.

Laboratory diagnostics of plague was carried out in compliance with valid operational guidelines and regulations. But its peculiarity consisted in the performance of diagnostic investigations secondary to antimicrobial therapy with application of preparations characterized by the expressed activity towards gram-negative microorganisms, including the agent of plague (ceftriaxone, ciprolet, and amikacin). The studies revealed that under antibiotic treatment during the early phase of infection the most effective method for the laboratory plague diagnostics was PCR. Based on the results of the assay it was possible to establish not only provisional, but also the final diagnosis in a patient. Obtained was genetic characteristics of the strains isolated from the patient and the marmot, withdrawn at the patient’s place, using techniques of molecular-genetic analysis, in particular PCR, multilocus VNTR, and multilocus and genome-wide sequencing. Thereupon the strains were attributed to antique biovar of the main subspecies of plague agent. In addition, close relation to Y. pestis of the main subspecies isolated in the same focus in 2012 and to the strains from Mongolian Altai and Tuvinian mountain focus was determined based on phylogenetic analysis of the isolates.

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.

Performed is a complex microbiological, molecular-genetic and mass-spectrometric identification of Yersinia pestis main ssp. strain, which was isolated for the first time in the history of surveillance over the Altai mountain natural plague focus in June, 2012. Determined is its high universal virulence. Plasmid screening, multi-locus VNTR- and mass-spectrometric analyses have revealed the strain to be more closely related to the plague agent variant, circulating in the territory of the natural focus Khuukh-Serkh-Munkh-Khairkhan, Bayan-Ul’giisk aimak, Mongolia.

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.

Influence of a cobalt-containing nanobiocomposite on basis of arabinogalactane on morphological changes in immunocompetent organs of the experimental animals at peroral and parenteral introduction was studied, by a computer program. «Morphometry». Comparative estimation, of morphological and. histological changes in spleen and. regional lymph, nodes of the outbred. white mice was performed.

Effects of Y. pestis EV antigenic complexes upon the functional activity of the phagocytic cells of guinea pig and white mice were assayed to demonstrate that the preparation constructed on the basis of the F1 antigen, Y. pestis EV membrane fraction and the Siberian larch arabinogalactane (AG) used as an immunomodulator, was able to increase the functional activities of the phagocytic system in test animals (guinea pigs), enhancing the adhesive and absorptive activity of the peritoneal macrophages and the intensity of active oxygen and nitrate monoxide production, as well as stimulating the activity of myeloperoxidase and the synthesis of non-enzyme cationic polymorphonuclear leucocytes. The antigenic complex prepared on the basis of the F1 antigen, Y. pestis EV membrane fraction and AG, was also shown to exert a stimulating effect on cytokine-inducing function of white-mouse macrophages expressed in the increased production of IL-1, IL-6 and FNO-α cytokines.

Arabinoganactane isolated from Siberian larch (Larix sibirica) and its iron and cobalt nanobiocomposites were selected as immunomodulators to elucidate the possibility of intensification of specific immunity against plague. Comparative morphometric analysis of immune system organs of white mice inoculated with live plague vaccine (LPV) and its combination with immunomodulators was performed. Experimental data indicate that arabinogalactane and its nanobiocomposites used in combination with LPV increase immunocytopoetic function of immune system organs to larger extent than LPV.