[Studying the possibility of respiratory immunization against tick-borne encephalitis]. / Izuchenie vozmozhnosti respiratornoi immunizatsii protiv kleshchevogo éntsefalita.

There are known 3 likely mechanisms of virus conveyance into the central nervous system (CNS). These include hematogenic penetration, spread along the peripheral nerves, and the olfactory pathway which begins from the infected olfactory neuroepithelial cells. The possibility of viral spread into CNS via the olfactory pathway was shown for the representatives of togaviruses, herpesviruses, coronaviruses, rhabdoviruses, and for some others. This study suggests that the olfactory pathway of viral conveyance into CNS may be blocked by specific mucosal antibodies in the nasal mucosa. The recombinant TK- variant of WR vaccinia strain with inserted genes coding structural and nonstructural proteins of TBE virus is accumulated in the branches of the respiratory tract only while the parenteral vaccinia strain is detected in the brain regions, spleen, respiratory tract, and in blood. The protective activity of recombinant strain and inactivated TBE vaccine after mice immunization by escarification or intranasally, or subcutaneously was comparatively studied. The findings indicate that intranasal immunization by recombinant strain is the most protective against intraperitoneal challenge by TBE virus. The mucosal and humoral immune response that was induced by intranasal immunization seems to provide the highest levels of protection, which was experimentally observed.

[Certain pathogenetic characteristics of a disease in monkeys in infected with the Marburg virus by an airborne route]. / Nekotorye patogeneticheskie kharakteristiki zabolevaniia obez'ian, aérogenno infitsirovannykh virusom Marburg.

Time course of Marburg virus (strain Popp) accumulation and changes in hematological parameters were studied in aerosol infected M.rhesus monkeys. The lungs were the first organ in which the virus was detected after respiratory infection of monkeys. Four days after inoculation the virus was detected in the liver, spleen, blood, and thymus. Six days after inoculation the virus was present in virtually all organs and secretions. The period of fever was associated with manifest leukopenia in primates. Blood clotting time drastically increased by the moment of animal death.

[Clinical-virusological characteristics of disease in guinea pigs, infected by the Marburg virus aerogenically]. / Kliniko-virusologicheskie kharakteristiki zabolevaniia morskikh svinok, aerogenno infitsirovannykh virusom Marburg.

Marburg virus (strain Popp) was found to accumulate in various organs of guinea pigs after aerogenic infection. At the initial stage of the infection primary multiplication of the virus took place in the lungs. The presence of the virus in bronchopulmonary washings 2-3 days after infection, leukopenia and hyperthermia 4 days after infection are the earliest virological and clinical signs of disease in aerogenically infected guinea pigs.

[Study of the treatment-prophylactic effect of immunomodulators in experimental infections, caused by Marburg, Ebola, and Venezuelan equine encephalitis viruses]. / Izuchenie lechebno-profilakticheskogo deistviia immunomoduliatorov pri éksperimental'nykh infektsiiakh, vyzvannykh virusami Marburg, Ebola i Venesuél'skogo éntsefalomielita loshadei]

Therapeutic and prophylactic effects of immunomodifiers ridostin, reaferon, and polyribonate used alone and in various combinations were assessed in experiments on guinea pigs infected with Venezuelan equine encephalomyelitis (VEE) (strain Trinidad), Marburg (strain Popp), and Ebola (M/C-8 variant of Zaire strain) viruses at doses 5 to 20 respiratory LD50 through the respiratory airways. Urgent prophylactic simultaneous intramuscular and intranasal administration of ridostin protected the animals infected with Marburg virus (p = 0.1) and prolonged their life span by 2.4 days (p = 0.15). In Ebola infection a combination of ridostin and reaferon appreciably prolonged the mean life span: by 2.9 days (p = 0.04). In VEE ridostin alone or in combination with reaferone appreciably increased the share of survivors; ridostin with reaferon and polyribonate notably prolonged the mean life span of infected animals. None of these drugs or combinations produced an appreciable therapeutic effect in any of the studied infections.

[Sensitivity of white mice to influenza virus (A/Aichi/2/68) in aerogenic infection]. / Chuvstvitel;nost' belykh myshei k virusu grippa (A/Aichi/2/68) pri aérogennom zarazhenii.

Polydispersed aerosols from allantoic fluid of chick embryos induced with influenza virus with different median weight aerodynamic diameters of corpuscles (0.5, 0.8, 1.1, 2.2, and 6.0 mu are effectively deposited in respiratory organs of mice weighing 18-19 g. The sensitivity of mice of different weight to aerogenic infection with influenza virus (strain A/Aichi/2/68) was virtually the same. The efficacies of aerogenic 50% infective and lethal doses (1.8-2.5 lg) for mice of the same weight were different. The sensitivity of mice to aerogenic infection and of developing chicken embryos to the virus (ID50 = EID50) is the same. Mice weighing 10-19 g can be infected via airways with adapted influenza virus in studies of therapeutic and prophylactic effects of drugs.

[The efficacy of the emergency prophylactic and therapeutic actions of immunomodulators in experimental filovirus infections]. / Effektivnost' ékstrenno-profilakticheskogo i lechebnogo deistviia immunomoduliatorov pri éksperimental'nykh filovirusnykh infektsiiakh.

The study of the preventive and therapeutic action of some immunomodulators (ridostin, reaferon and polyribonate) used alone and in combinations was conducted on laboratory animals infected aerogenically by Marburg or Ebola virus. It was found that special preventive intranasal and intramuscular administration of ridostin provided protection of the animals infected by Marburg virus (p = 0.1) and an increase in their mean lifespan by 2.4 days (p = 0.15). In the Ebola infection combined administration of ridostin and reaferon caused an essential increase in the mean lifespan of the animals by 2.9 days (p = 0.04). None of the tested drugs had any significant positive effect when used in various combinations according to the treatment schemes in Marburg and Ebola infections in guinea pigs.

[The efficacy of the therapeutic and prophylactic actions of immunomodulators in experimental infection due to the causative agent of Venezuelan equine encephalomyelitis]. / Effektivnost' lechebno-profilakticheskogo deistviia immunomoduliatorov pri éksperimental'noi infektsii, vyzvannoi vozbuditeliami venesuél'skogo éntsefalomielita loshadei.

The investigation of the prevention and treatment action of some immunomodulators (ridostin, reaferon and polyribonate) used alone and in combinations was conducted on laboratory animals infected aerogenically by Venezuelan equine encephalitis (VEE) virus. A lower death rate of the aerogenically infected mice (10-30 respiratory LD50) was observed after intramuscular injection of ridostin. The preventive affect of ridostin and ridostin + reaferon administered intranasally and intramuscularly was achieved in the aerogenically infected guinea pigs (10 respiratory LD50). The results of the study on the early virus reproduction in the animals were used for the choice of the treatment scheme. The immunomodulators had no effect when the treatment was started 1 day after the VEE virus infection.

[Dynamics of interferon induction in albino mice by interferon inducer ridostin administered by various routes]. / Izuchenie dinamiki interferonoobrazovaniia v organizme belykh myshei pri razlichnykh putiakh vvedeniia induktora interferona ridostina.

The time dependence of interferon production in blood, tissues of the respiratory tract, brain and olfactory tract of mice BALB/c was investigated after administration of the interferon inductor ridostin by various routes. Intraperitoneal injection of ridostin in a dose of 5 mg/kg induced intensive accumulation of interferon in the blood serum with the peak in 8 hours (2560 U/0.2 ml) while no interferon was detected in the tissues of the respiratory tract and brain of the animals. Intracerebral injection of ridostin in the same dose induced accumulation of interferon in both the tissues of the brain (maximum 160 U/0.2 ml in 24 hours) and the blood serum (maximum 1280 U/0.2 ml in 8 hours). After respiratory administration of ridostin interferon was detected only in the site of the administration in the tissues of the upper respiratory tract and lungs of the mice.