The aim of the investigation was to study in experiment total toxicity and immunological safety of a novel domestic therapeutic vaccine against recurrent respiratory papillomatosis and anogenital condylomatosis, the vaccine injected intramuscularly.Materials and Methods. we studied acute toxicity of the vaccine by the following parameters: clinical presentation of intoxication, median lethal dose size, the change of body weight of the surviving animals; chronic toxicity -by dynamics of general condition of the animals, body weight, hematological and biochemical indices of peripheral blood, functional status of central nervous system, cardiovascular system, kidneys, as well as pathomorphological changes of viscera.Allergenicity was studied by systemic and active cutaneous anaphylactic tests. we assessed immunotoxicity by direct a hemagglutination assay and a delayed-type hypersensitivity test, as well as by neutrophilic activity using luminal-dependent chemiluminescence. Proliferative activity of В-and Т-lymphocytes to lipopolysaccharides and concanavalin А (ConА) was estimated in a direct immunofluorescence test using immunocytochemical assay with anti-Ki-67 monoclonal antibodies.Results. Mean lethal doses (lD 50 ) were not reached in white outbread rats injected intramuscularly by the tested vaccine at a maximum possible single dose (25 ml/kg). Multi-dose administration to white outbread rats and chinchilla rabbits at doses of 0.043; 0.43; 0.86 ml/kg and 0.023; 0.23; 0.4 ml/kg respectively, did not cause significant damage of functional status of basal organs and systems of experimental animals.The findings of systemic anaphylaxis and active cutaneous anaphylactic response to the vaccine in albino guinea pigs at the doses of 0.033 and 0.33 ml/kg intramuscularly indicated the vaccine to exhibit no allergenic properties.Intramuscular vaccine injected to first filial hybrid mice (СВА×С57Bl/6)f 1 at the doses of 0.084; 2.5 and 25 ml/kg showed neither significant increase or decrease of inflammatory response intensity relating to reference values. The vaccine at the doses of 0.084 and 2.5 ml/kg did not cause any changes of vaccination titer (IgG), phagocytic activity, spontaneous or induced blastic transformation of lymphocytes compared to the control group. The vaccine administered at the dose of 25 ml/kg significantly reduced the antibody formation level relating to the controls, as well as produced a suppressive effect on spontaneous and induced phagocytic activity resulting in the significant reduction of ConА-induced proliferative activity of Т-lymphocytes by the number of Ki-67 positive cells compared to the control group.Conclusion. The animal study of different types of general toxicity of the vaccine against recurrent respiratory papillomatosis and anogenital condylomatosis, the vaccine injected intramuscularly, showed the vaccine to be low toxic and immunologically safe in the dose range from 0.033 to 2.5 ml/kg.

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Bacterial lysates may produce immunoregulatory effects in the inflammatory diseases that are not directly caused by infectious agents; they may also stimulate the immune response against pathogens which are not a part of the lysate composition. Imudon® is a polyvalent bacterial lysate that is available in orodispersible tablets. However, the influence of this drug product on aseptic inflammation and immune defense against the infectious agents, the antigens of which are not contained in this preparation have not been studied so far. The aim of this study, therefore, was to determine the anti-inflammatory and immunomodulating effects of Imudon® using the models of aseptic lymphadenitis (in Wistar rats) and pneumococcal pneumonia (in Balb/c mice), i.e., the conditions not related to the specific components of the bacterial lysate. Lymphadenitis was induced in rats by administration of λ-carrageenan into a cervical lymph node via an open operative approach. Whereas pneumonia was induced in mice by administering Streptococcus pneumoniae suspension intranasally. The choice of pneumococcus was determined by the absence of pneumococcal antigens in Imudon®, i.e., it cannot be a direct inducer of adaptive immune response against pneumococcal infection. Imudon® was administered intragastrically as a crushed tablet suspension following a therapeutic-preventive regimen (for 14 days daily until the induction of inflammation and for 3 [in the lymphadenitis model] or 5 days [in the model of pneumonia] in three doses thereafter). In the lymphadenitis model, Imudon® demonstrated both local and systemic anti-inflammatory responses manifested in the reduced number of circulating leucocytes and lower TNFα levels and by ameliorated histological features of inflammation in the operated lymph node. In rats, the anti-inflammatory effect was most pronounced when the product was administered at a dose of 2.2 mg/kg (equivalent to a human therapeutic dose) and 6.6 mg/kg. In the model of pneumonia, administration of Imudon® at 4.44 mg/kg (equivalent to a human therapeutic dose) and 13.32 mg/kg demonstrated a trend towards increased survival rate as compared to the control group. On Day 5 after infection Imudon® (4.44 and 13.32 mg/kg) decreased significantly the severity of inflammation and bacterial titer in the lungs. The titer of anti-pneumococcal immunoglobulins A in the bronchoalveolar lavage fluid were found to be higher in the Imudon® treated group (13.32 mg/kg) compared to control group. The results of this study showed high antiinflammatory and immunomodulatory activities of Imudon® and provided an insight into the mechanisms that underlie the clinical effects of this drug in various inflammatory diseases.