[Immunogenicity and safety of a prototype chemical anthrax vaccine in laboratory animal models].

AIM: Evaluation of immune stimulating and toxic effects of a vaccine prototype protein components. MATERIALS AND METHODS: Linear mice, guinea pigs and rabbits were immunized subcutaneously once or twice by recombinant protective antigen (rPA), S-layer protein (EA1) or their complex. Innate immunity structure activation was registered by changes in Toll-like receptor (TLR) expression. Adaptive immune response parameters were determined by established methods. Toxicity of the preparations was determined using flow cytofluorometry and densitomorphometry. RESULTS: The ability of rPA and EA1 to activate structures of innate immunity - TLR 2 and 6 - was established. Features of anti-PA antibody titer dynamics for each of the animal species was determined, a comparison with antibody formation during immunization with Bacillus anthracis STI- 1 was carried out. 2 immunizations ofbiomodels with a complex preparation combined with an adjuvant provides protection from infection by a test-strain that is comparable with protectivity of a live vaccine. Evidences regarding damaging effect of rPA and EAI on cells and tissues of macro organism were not detected throughout the study. CONCLUSION: Aprototype of a chemical anthrax vaccine under development has high immunogenicity and its protein components are not toxic for laboratory animals based on the results of complex testing.

[Morphofunctional evaluation of the state of cells of APUD-system biomodel during anti-plague vaccine process].

AIM: Study reaction of cells of APUD-system of lymphoid organs and intestine of guinea pigs at the stages of morpho- and immunogenesis in response to administration of Yersinia pestis EV Research Institute of Epidemiology and Hygiene (RIEH) line vaccine strain. MATERIALS AND METHODS: Vaccine process was modeled in guinea pigs during subcutaneous infection of animals with culture of Yersinia pestis EV RIEH line vaccine strain. Pieces of thymus, spleen, lymphatic nodes and an area of duodenum were taken for histological study. The preparations were stained by solution of hematoxylin and eosin, impregnated with silver by Grimelius and Masson in Hamperl modification. RESULTS: Dose-dependent character of effect of anti-plague vaccination on reaction of apudocytes in immunocompetent organs and duodenum biomodels was established, that indirectly reflects the direction of processes of immunogenesis in central and peripheral organs of immune system. Changes in quantity and morphofunctional state of apudocytes in the intestine of immunized guinea pigs gives evidence of the interest of this segment of APUD-system in the processes of immunogenesis during plague. CONCLUSION: Range of changes of quantity and functional state of apudocytes in lymphoid organs and intestine of animals during anti-plague vaccination was established. Quantitative parameters of morphofunctional state of intestine adipocytes that may be used for characterization of the intensity of adaptation-compensatory process in the organism of biomodels during modeling of any experimental vaccine process as well as an additional indirect indicator during evaluation of reactogenicity of live anti-plague vaccines were determined.

[Morphometric characteristics of tularemia infectious process in the organism of immunized guinea pigs].

AIM: Morphometric characteristic of organ and system state of guinea pigs immunized with live tularemia vaccine during infection with virulent culture of tularemia. MATERIALS AND METHODS: Morphometric study of histological material from immunized guinea pigs infected subcutaneously at day 30 with a culture of virulent tularemia strain was performed. A standard scheme of sampling and preparation of morphological material and staining of final semifine section with hematoxylin and eosin, impregnation with silver by Masson in Gamperl and Grimelius modificationwas used. Morphometric study was performed by using "Densitomorphometry" program. RESULTS: Morphometric parameters that characterize functional state of organs and systems in immunized, immunized with consequent infection and infected guinea pigs were established. Reactive processes that take place in the infected animal organism against the background of prior immunization fit into the range of adaptation-compensation reactions. CONCLUSION: The morphometric study carried out allowed to adequately evaluate the state of functionally important systems of the organism of experimental animals, this allows to consider perspective the wider use of morphometric analysis in experimental morphology.

[Complex morphological approach to assessment of protective properties of preparations for cholera specific prophylaxis].

Using developed scheme, complex study of protective properties of avirulent recombinant strain Vibrio cholerae El Tor Inaba KM 184 was performed. Necessity for broadening of standard procedure of testing of cholera vaccines protective properties by using of quantitative methods of assessment of morphological changes and state of biomodel's functional systems, which could increase the information value of assessment of studied vaccines, was experimentally substantiated.

[Comparative pathomorphological assessment of the action of Vibrio cholerae serogroups 01 and 0139]. / Eksperimental'nye dannye sravnitel'noi patomorfologicheskoi otsenki deistviia kholernykh vibrionov 01 i 0139 serogrupp]

The pathomorphological picture of experimental infection caused by the infective agent of cholera was shown to have some specific features observed in infections caused by vibrios belonging to the serogroups under study. Infection caused by V. cholerae of serogroup O139 induced some morphological changes in the gastrointestinal tract which were quite characteristic of this disease, but inflammatory changes with the prevalence of proliferative infiltrative processes came to the foreground simultaneously with less developed processes of edema and dystrophic lesions of enterocytes. These specific morphological features in animals infected with V. cholerae of serogroup O139 appeared to be probably due to the production of new surface structures by these strains.

[Apudocytes in experimental cholera vaccination]. / Sostoianie apudotsitov pri protivokholernoi vaktsinatsii.

The morphofunctional state of apudocytes in the gastrointestinal tract and immunocompetent organs (spleen, mesenteric lymph nodes) of mice immunized with chemical bivalent cholera vaccine was studied. The study revealed that the APUD system of the intestine and the argyrophil elements of the immunocompetent organs of white mice gave a response to the oral administration of commercial cholera vaccine. The reaction of the APUD system of the gastrointestinal tract was manifested by a significant increase in the number of apudocytes and their greater synthesizing activity in the immunized animals during the period of maximum immunological transformation of the macroorganism. The immunization of mice with Vibrio cholerae facilitated the maintenance of homeostasis in the macroorganism and prevented appearance of morphological disturbances in its organs and system after subsequent challenge with V. cholerae.

[The APUD-system function of the intestines and the morphological changes in the internal organs of adult rabbits infected with toxigenic Vibrio cholerae]. / Sostoianie APUD-sistemy kishechnika i morfologicheskie izmeneniia vo vnutrennikh organakh vzroslykh krolikov, zarazhennykh toksigennymi kholernymi vibrionami.

V. cholerae infection with clearly pronounced diarrhea was reproduced in adult rabbits with the use of the RITARD system. The state of the APUD system of the intestine of the animals and morphological changes in internal organs in experimental cholera were described. As noted in this study, the manifestation of changes in the intestine and other organs, as well as the reaction of apudocytes to V. cholerae infection, were linked with the intensity of diarrhea and the time of the death of the animals.

[The comparative characteristics of the pathogenic action of Vibrio cholerae of the non-O1 group O139 serovar and of the O1 group on the intestinal APUD system of suckling rabbits]. / Sravnitel'naia kharakteristika patogennogo deistviia kholernykh vibrionov ne O1 gruppy O139 serovara i O1 gruppy na APUD-sistemu kishechnika krol'chat-sosunkov.

The comparative study of the enteropathogenic action of V. cholerae strains of group non-O1, serovar O139, and group O1 with different virulence on the APUD system of the intestine of suckling rabbits after intraenteral infection revealed that V. cholerae of group non-O1 induced inflammatory changes in the intestine and the pronounced toxic lesion of parenchymal organs. This was accompanied by a decrease in the number of apudocytes and an increase in the functional tension of the APUD system. After the infection of the animals with V. cholerae of group O1 changes in the APUD system and internal organs directly depended on the virulence of the microbes and the infective dose.

[The effect of choleragen poisoning on the intestinal apudocytes of gnotobiotic minipigs]. / Vliianie kholerogennoi intoksikatsii na apudotsity kishechnika gnotobioticheskikh mini-porosiat.

Intragastric administration of the cholera toxin to gnotobiotic mini-pigs results in cyclic morphofunctional alterations of intestinal apudocytes followed by their degranulation, a decrease in their number from 1 to 3 hrs and after 18 hrs, while a slight increase in their number occurred from 3 to 12 hrs. The response of APUD-system cells is similar in large and small intestine. Products of apudocyte secretion may be involved in the diarrheogenic effect of the cholera toxin.