Dynamics of Changes in the cAMP/cGMP Concentration Ratio in the Thymus and Spleen of Laboratory Mice during Vaccination against Plague and Tularemia against the Background of Immunomodulation.

Vaccine strains Yersinia pestis EV NIIEG at a dose of 103 CFU and Francisella tularensis 15 NIIEG at a dose of 102 CFU induced changes in the concentration of cyclic nucleotides in the thymus and spleen of white mice. Antigen-induced changes in the cAMP/cGMP ratio in immunocompetent organs had a phase or oscillatory character, which seems to be related to the regulation of postvaccination immunoreactivity in the body. Synthetic organoselenium compound 974zh stimulated an increase in the amplitude of cAMP/cGMP oscillations, indicating its stimulating effect on the immunogenic properties of vaccine strains at doses an order of magnitude below the standard doses.

Relationship between HLA-II Gene Polymorphisms and Immune Response in COVID-19 Survivors and Volunteers Vaccinated against This Infection.

The polymorphism of HLA class II genes was studied in COVID-19 survivors and vaccinated people. Six allelic variants of DQA1, 10 of DQB1, and 11 of DRB1 were identified. The DQA1*05:01 allele predominated in vaccinated volunteers and the DQA1*02:01, *01:03, and DQB1*06:02-8 alleles predominated in convalescents. In the groups with DQA1*01:01, *05:01 and *06:01 alleles, a high proportion of individuals seropositive for SARS-CoV-2 S protein was found. In the group with DQA1*02:01 allele, 40% of volunteers were found to have IgM and a significantly lower quantity of IgG to N protein of coronavirus. Comparative analysis showed a statistically significant increase in IL-10 levels in carriers of the DQA1*01:01 allele, which may indicate the influence of this allele on cytokine production. Further study of the immune response indices and their association with HLA class II gene polymorphism will provide better understanding of the mechanisms of COVID-19 immunogenesis.

The Influence of the Synthetic Organoselenium Preparation 974zh on the Immunogenic Activity of Yersinia pestis EV Vaccine Strain NIIEG.

In the present study, a stimulating effect of a new synthetic organoselenium compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonandibromide (974zh) on the immunogenic activity of the vaccine strain Yersinia pestis EV NIIEG was revealed. After infection with the virulent plague strain, the survival rate of laboratory mice immunized with the vaccine strain grown on Hottinger's agar in the presence of 974zh (300 µg/ml) increased in comparison with control animals immunized with the Y. pestis EV NIIEG culture grown on agar without the studied compound. Plasmid screening of cultures grown on medium with and without 974zh showed that plasmid DNA of Y. pestis EV culture grown in the presence of 974zh had broader bands in the control grown without 974zh. This phenomenon can indicate activation of replication of plasmid DNA of Y. pestis EV under the influence of the experimental compound.

Peculiarities of Humoral Immunity Formation in Medical Institution Employees Recovered from or Vaccinated against COVID-19 in Irkutsk.

We performed a seroepidemiological survey of the level and structure of population immunity to SARS-CoV-2 among employees of medical institution in the Irkutsk region during the COVID-19 pandemic. Seroprevalence assessment was organized from May 2020 to April 2021. The level of antibodies to SARS-CoV-2 was measured by ELISA. It was found that 139 (46%) of 299 examined workers were seropositive, including 50 (36%) vaccinated against COVID-19, 75 (54%) patients diagnosed with COVID-19, and 14 (10%) asymptomatic cases of SARS-CoV-2. The results obtained should be taken into account when predicting the dynamics of the epidemic process and organizing preventive (antiepidemic) measures, including vaccination.

Effect of a Synthetic Organoselenium Compound on Post-Vaccination Immunopoiesis in the Red Bone Marrow and Cell Composition of Peripheral Blood of White Mice Vaccinated with Yersinia pestis EV.

We studied the effect of an experimental synthetic organoselenium compound 2,6-dipyridinium- 9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the cell composition of the red bone marrow and peripheral blood in white mice. The study drug co-administered with Yersinia pestis EV vaccine strain (103 CFU) potentiated maturation and migration of mature neutrophils from the bone marrow into the circulation. Reducing the dose of the live vaccine and the anti-inflammatory properties of the study drug made it possible to reduce the allergic reaction during the vaccination process.

Antigen-Specific Activation of Blood Lymphocytes in Mice Immunized with Brucella abortus 19 BA.

We studied the expression of activation markers CD25 and CD69 by blood lymphocytes in white mice vaccinated with Brucella abortus 19 BA in antigen-specific tests in vitro. During incubation of blood lymphocytes with brucellosis polysaccharide-protein antigen, a statistically significant increase in the expression of CD25 by B cells and CD69 by T cells was observed; brucellin increased the expression of CD25 by B and T cells. Comparative analysis of the action of antigen preparations B. abortus showed that only brucellin has antigen-specific activity against CD19+CD25+ cells. The used method can be considered as a promising test for evaluation of the effectiveness of brucellosis immunoprophylaxis, which substantiates the need for further research.

Immunotropic Properties of an Experimental Synthetic Selenium-Organic Compound.

We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.

Effect of Synthetic Organoselenium Drug on the Degree of Pathological Changes in the Organs of White Mice Immunized with Tularemia and Brucellosis Vaccines.

We studied the effect of the organoselenium compound 2,6-dipyridinium-9-selenium-bicyclo[ 3,3,1]nonan dibromide (974zh) on the severity of pathological changes in the organs of experimental animals immunized with live tularemia and brucellosis vaccines. It was found that 974zh reduced reactogenicity of vaccines for experimental animals. Our findings indicate the prospects for further studies of the effects of 974zh on the functional state of experimental animals.

Effects of Thermoextracts of Brucella S and L Forms on Lipid Peroxidation and Antioxidant Defense in Organs of Laboratory Animals.

The dynamics of LPO marker malondialdehyde formation and peroxidase-destroying activity was studied in homogenized organs of guinea pigs, immunized with thermoextracts from S and L forms Brucella abortus I-206. The L form brucella thermoextract exhibited a lower reactogenicity and adequately activated the antioxidant system, due to which the destructive effects of ROS could be partially neutralized during the vaccinal process.

Effect of Metal-Containing Nanocomposites on Functional Status of the Thymus in Experimental Animals.

The effects of nanostructurized composites argentogalactomannan and argento-poly-1-vinyl-1,2,4-triasole on the kinetics of T cell maturation in the thymus of albino mice were studied. These nanocomposites stimulated the formation of CD3+CD4+CD8- and CD3+CD4-CD8+ cells from CD3-CD4-CD8- cells, the effect of argentogalactomannan was more potent. The efficiency of these compounds as agents improving the defense potential deserves special studies.

Immunogenesis in White Mice Infected with Yersinia pestis with Different Plasmid Composition.

Morphological changes in the immunocompetent organs of white mice with experimental plague infection manifested in activation of the immune response of different degree and pathological process of different severity that depended on the plasmid composition of Y. pestis. Widening of the T-dependent zones in the immune organs of white mice infected with isogenic strains of Y. pestis with different plasmid composition attests to activation of cellular immunity. Our findings allow considering Y. pestis subsp. altaica I-2948/3, Y. pestis subsp. pestis I-3479 and Y. pestis subsp. pestis I-3480 as promising candidates for vaccine strains.

[Phagocytic functional and metabolic activities in the interaction with F. tularensis subspecies of various virulence].

There is evidence that the facultatively intracellular pathogen affects the functional capacity of phagocytes, which is associated with their bactericidal against a tularemic microbe with varying phenotypic properties. The tularemic microbe of the subspecies Francisella subsp. tularensis and F. tularensis subsp. mediaasiatica is shown to influence the phagocytic capacity of immunocompetent cells, resulting in incomplete phagocytosis. This is corroborated by the lower functional activity of neutrophils and macrophages in the interaction with tularemic microbe of the subspecies tularensis and mediaasiatica to a greater extent than in that with the representatives of other studied F. tularensis subspecies. The low content of cationic protein and the suppressed activity of NO-synthase may be associated with the loss of activity of the enzyme and cationic protein during phagocytosis of the tularemic microbe. The findings are of prognostic value in characterizing the severity of a pathological process caused by F. tularensis and in designing diagnostic and prophylactic agents.

[The activity of the phagocytic bactericidal systems in intact guinea pigs and in guinea pigs immunized against tularemia]. / Aktivnost' bakteritsidnykh sistem fagotsitov u intaktnykh i immunizirovannykh protiv tuliaremii morskikh svinok.

The activities of NADP-oxidase and glucose-6-phosphate dehydrogenase in mononuclear phagocytes and polymorphonuclear leukocytes (PML) during the phagocytosis of Francisella tularensis and the influence of immunization of on the activity of oxygen-dependent metabolism were studied. The phagocytosis of F.tularensis was found to be accompanied by a rise in the activity of NADP.H-oxidase and glucose-6-phosphate dehydrogenase. In the process of immunogenesis the rearrangement of the enzymatic system ensuring the antimicrobial action of phagocytes occurred. Macrophages exhibited higher enzymatic activity than PML.

[Characteristics of phagocytosis of Yersinia pseudotuberculosis with various sets of plasmids]. / Osobennosti fagotsitoza Yersinia pseudotuberculosis s raznym naborom plazmid.

The study used the selected aplasmid strain of Y. Pseudotuberculosis 53 and I-716, which contains plasmids that have molecular weights of 48 and 82 mD, and I-727 that has only virulence plasmid pYV48. The study has indicated that the fact that Yersinias have pVM82 and pYV48 enhances their resistance to phagocytosis. The Y. pseudotuberculosis strains carrying these plasmids suppress the responsiveness of phagocytes, inhibit an "oxidative explosion", lower the activities of superoxide dismutase and myeloperoxidase, thus suppressing their bactericidal capacity.

[Comparative study of immunomodulating effects of natural experimental preparations on phagocytosis of Yersinia pseudotuberculosis]. / Sravnitel'noe izuchenie immunokorregiruiushchikh svoistv éksperimental'nykh preparatov prirodnogo proiskhozhdeniia pri fagotsitoze Yersinia pseudotuberculosis.

To correct defects of the body's phagocytic system, the authors used experimental agents, such as vital activity products of plant cells, which were obtained by biotechnology. These included arabinogalactan, syringin, K-212, and DFEGP. The study agents activate the oxidative metabolism of macrophages, the production of active forms of oxygen, and thus enhance its bactericidal effect against Yersinia pseudotuberculosis. Syringin and arabinogalactan produce a more pronounced stimulating macrophageal effect in Yersinia pseudotuberculosis phagocytosis than do K-212 and DFEGP. The findings indicate that further studies of the effects of these tested and other agents on humoral and cellular immunity are required.