Local and Systemic Functional Responses of Mouse Macrophages to Intravaginal Infection with Type 2 Herpes Simplex Virus and Vaccination.

Activity of cathepsin D and phagocytosis of macrophages from vaginal lavage fluid, peritoneal exudation, and spleen were studied in mice of sensitive (DBA/2) and resistant (BALB/c) lines after intravaginal infection with type 2 herpes simplex virus and vaccination. Activity of cathepsin D and intensity of phagocytosis (irrespective of the macrophage source) and their ratio in BALB/c mice in early terms after infection were close to the control levels taken as a unit. In DBA/2 mice, these parameters and their balance were shifted and changes in cathepsin D activity depended on the time after challenge.

[Vaccines as an approach to the immunocorrection in herpetic infections].

Development of vaccines for immunologic correction in herpetic infections is an important problem that raises a growing concern worldwide. The data on the experimental studies of the efficacy of an inactivated whole-virion vaccine against herpes simplex viruses types 1 and 2 (HSV-1 and -2) using an animal model are discussed. The results of the multiyear application of the vaccine to ophthalmology and dermatology practice are also presented.

[Immunomodulators and specific inactivated vaccines in urgent prophylaxis under experimental arboviral infection].

A reliable protective activity of the home-manufactured immunomodulators (ridostin, polyribonate glucosemuramyl-dipeptide, Mylife, and peptidoglycane-160) was detected in mice. The mice were infected with the equine eastern encephalomyelitis virus (EEEV, an alphavirus), or with the tick-borne encephalitis virus (TBEV), or the yellow fever (YF) virus (both flaviviruses). The effect of the urgent vaccination reliably increases when the vaccination is combined with the immunomodulators listed above.

[Efficiency of coadministration of immunomodulators and vaccine in an experiment on tick-borne encephalitis].

Experiments on a tick-borne encephalitis (TBE) model in CBA and BALB/c mice demonstrated that immunomodulators (ridostin, polyribonate, and peptidoglycan-160) and a specific vaccine against TBE were significantly effective in increasing the level of a protective effect and life expectancy in the experimental group as compared to the control group. The findings allow one to recommend the immunomodulator ridostin in combination with the inactivated vaccine for the emergency prophylaxis of TBE in its virus-infected subjects in the foci of infection.

[Combined effects of immunomodulators and specific inactivated vaccines against alpha- and flavivirus infections].

The combined effects of immunomodulators, such as ridostin, polyribonate, glucose muramyl dipeptide, and peptidoglycan-160, and specific vaccines on survival of mice with alpha- (eastern equine encephalitis) and flavivirus (tick-borne encephalitis (TBE) infections were found to be significant. In alphavirus infection, the combined effects of the specific vaccine and ridostin were accompanied by increases in specific humoral immunity (specific antibodies) and cellular immunity (adoptive transfer of immune lymphocytes). The concurrent use of the specific vaccine and the immunomodulator ridostin is recommended in clinical trials of TBE in the foci of infection.

[Inactivated herpes simplex virus types 1 and 2 divaccine as an agent for effective immunoprophylaxis of recurrent genital herpes].

Prevention of recurrent genital herpes with the inactivated herpetic divaccine Vitaherpavac against herpes simplex virus types 1 and 2 has a number of advantages over the most commonly used symptomatic therapy: it ceases or significantly reduces the number of recurrences and accordingly prolongs a relapse-free interval, abolishes viremia and the manifestations of clinical symptoms of recurrences, induces no dependence to the vaccine. Coadministration of the Vitaherpavac vaccine and the immunomodulator Giaferon has been shown to have some advantage over vaccination only. The new formulation of the agent as suppositories (per rectum) not only enhances the immunogenicity and protective properties of the vaccine, but also reduces the frequency of its application and makes more convenient for patients to use.

[Vitaherpavac is the first Russian herpes simplex virus vaccine obtained on the Vero B continuous cell line].

Vitaherpavac, a dry inactivated herpes simplex virus (HSV) culture vaccine, has been obtained, by using the Vero B continuous cell line as a substrate for accumulation of herpes simplex virus types 1 (US strain) and 2 (VN strain). Vitaherpavac and the similar vaccine Herpovax made by the Research Institute of Vaccines and Sera, Saint Petersburg (for which preparation a primary trypsinized chick embryo cell culture used as a substrate for accumulation of HSV types 1 and 2), underwent comparative clinical trials. The tolerability and therapeutic effectiveness of the vaccine were tested in patients diagnosed as having chronic frequently recurring herpes.

Functional activity of peritoneal macrophages from sensitive and resistant mouse strains during intravaginal infection with herpes simplex virus type 2 and mucosal vaccination.

In the early period after intravaginal infection with herpes simplex virus type 2 (2 h), macrophages from sensitive DBA/2 mice were characterized by higher capacity to engulf the antigen, decreased function of the lysosomal apparatus, lower activity of cathepsin D, and reduced oxygen metabolism compared to cells from resistant BALB/c mice. Mucosal vaccination with herpes vaccine and hyaluronic acid promoted the increase in functional activity of macrophages and improved survival of sensitive mice (by 60%).

[Antiviral activity of Bacillus intermedius RNAase in guinea-pigs and rabbits infected with outdoor rabies virus].

Single injection of Bacillus intermedius RNAase in a dose of 5 mg/kg could protect 40 and 50-70% of the outdoor rabies virus-preinfected guinea-pigs and rabbits, respectively. In the control group there were 100 and 75-100% deaths of the RNAase-untreated guinea-pigs and rabbits, respectively. Animal protection was observed only when RNAase was injected into the site of viral administration.

3D molecular modeling, free radical modulating and immune cells signaling activities of the novel peptidomimetic L-glutamyl-histamine: possible immunostimulating role.

An original representative of the patented by author family of histamine-containing peptidomimetics L-glutamyl-histamine (L-Glu-Hist) was synthesized and characterized as a biologically active compound with a role of cytokine mimic leading to cellular responses of improved specificity. The study assesses the ability of L-Glu-Hist to affect molecular modeling, modulate free radical activity and influence immune cell signaling. The energy-minimized 3D conformations of L-Glu-Hist derived from its chemical structure resulted in stabilization for Fe2+ chelating complexes.

[Herpesvirus infection in patients with chronic glomerulonephritis].

Virological examinations of blood, urine and saliva in 75 patients with chronic glomerulonephritis (CG) revealed, in 95% of them, herpes-virus infections caused by herpes simplex virus, type 1 (34.4%), herpes simplex virus, type 2 (2.6%) and cytomegalovirus (12%) or mixed infections (46%).

Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine.

An original representative of histamine-containing peptidomimetics L-glutamyl-histamine (L-Glu-Hist) was synthesized and characterized as a cytokine mimic leading to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure resulted in stabilization for Fe(2+) chelating complexes. L-Glu-Hist accelerated the decrease of ferrous iron in the ferrous sulphate solution in a concentration-dependent mode and showed the ferroxidase-like activity at concentrations less than 3 mm in the phenanthroline assay, whereas in the concentration range 3-20 mm L-Glu-Hist restricted the availability of Fe(2+) to phenanthroline due to binding of ferrous ions in chelating complexes.

[The antiviral activity of RNAse Bacillus intermedius in experiments with mice preinfected with street rabies virus].

RNAse Bacillus intermedius, when administered once and according to 11 repeated experiments, protected the preliminarily infected CBA mice with street rabies virus (protection of 40-67%; p < 0.01-0.001).

[Antiviral activity of human recombinant gamma-interferon and recombinant hybrid protein of tumor necrosis factor-alpha-thymosin-alpha1 on models of herpes-virus and cytomegalovirus infection in vitro].

The conducted studies showed a certain efficiency of gene-engineering preparation of IFN-gamma and TNF-T in virus infections caused by herpes simplex virus 2 (HSV-2) and cytomegalovirus (CMV) in cell cultures of human embryo fibroblast (HEF). The drugs have no viricidal action. IFN-gamma, when used according to the treatment scheme in vitro, proved to be more effective versus TMF-T both in HSV-2 and in CMV.

[Polymorphism of herpes simplex virus type 1 and 2 DNA from laboratory strains and clinical material from patient with genital herpes].

Polymerase chain reaction (PCR), that can amplify a fragment of the DNA-polymerase gene of 4 herpes viruses, i.e. herpes simplex viruses, type 1 (HSV-1), herpes simplex viruses, type 2 (HSV-2), Epstein-Barr virus and cytomegalovirus, was made use of to study the genetic polymorphism of HSV-1 and HSV-2 strains.

[The antiviral activity of peptide immunomodulator "Gepon" in experimental infections caused by herpes simplex viruses types 1 and 2].

Experimental data are reported on the antiviral activity of peptide immune-modulator "Gepon" in infections caused by herpes simplex virus (HSV), types 1 and 2, in vitro and in vivo. The drug proved to be non-toxic and did not possess any viricidal action. Its antiviral effect was registered in experiments with a multiple-infection cells' culture.

[The antiviral activity of the peptide immunomodulator "Gepon" in experimental models of street rabies virus].

Intracerebral injections of the Gepon drug were shown to be non-toxic when administered to outbred white mice, 0.01-0.1 micrograms.

[Virus isolated in the human blood leukocyte culture and its interaction with hepatitis C and G viruses].

Electrone-microscopic investigations are indicative of that the cultures of healthy donors, stimulated by phytohemagglutinin (PHA), can be successfully used to study the etiology of parenterally transmitted hepatitis. An electronic-microscopic study of a virus, isolated from the blood serum of a patient with hepatitis on the basis of the PHA-stimulated human leukocyte cultures and named a hepatitis leukocytic virus (HLV), enabled, by using the negative contrasting method, to detect viral particles of the hexagonal shape, sized 50-65 nm, with a coating divided by a 4-5 nm light space. Therefore, the HLV was described as belonging to the Flaviviridae family.

[Combined use of killed vaccines and immunomodulator ridostin for urgent prevention of epidemic stomatitis, Aujeszky disease and carnivore plague in experiment].

Results of experimental studies of mice and pigs infected with foot-and-mouth disease virus, minks infected with Aujeszky's disease virus, and dogs infected with canine distemper virus are described. In animals with foot-and-mouth disease and Aujeszky's disease, combined treatment with killed vaccine and immunomodulator Ridostin by the scheme of urgent prophylaxis (3 days before infection) caused 75% (foot-and-mouth disease) and 100% (Aujeszky's disease) prevention of animal death and development of generalized infection. The use of Ridostin by the scheme of urgent prophylaxis in a canine distemper infection focus arrested clinical symptoms of the disease in 50% of animals received immunomodulator.

[Therapeutic effect of gefin, a new antiviral drug, in experimental genital herpes ].

Antiviral activity of Gefin was studied in guinea pigs infected with herpes simplex virus (HSV-2). Up to 54.9% animals challenged with HSV survived after 7-day treatment with Gefin (3 local applications a day).

[The development and testing of test systems for the determination of herpes simplex virus and cytomegalovirus antigens by lanthanide immunofluorescence analysis].

On the basis of the lanthanide immunofluorescent assay (LIFA) test systems for the determination of herpes simplex virus (HSV-LIFA) and cytomegalovirus (CMV-LIFA) antigens have been developed. The test system HSV-LIFA includes the sandwich of monoclonal antibodies (McAb) HSV A.3.

[Mechanisms for the therapeutic effect of herpes polyvaccines in chronic ophthalmic herpes and genital herpes].

Commercial inactivated culture polyvaccine against herpes simplex viruses (types 1 and 2) developed at D. I. Ivanovsky Institute of Virology promoted cessation of viremia.

[Development of a suppository form of the interferon inducer poludan and potentiation of its action by hyaluronic acid].

A promising dosage form of interferon inductor poludan has been developed for the treatment of patients with genital herpes and ophthalmic herpes: suppositoria. High interferon-producing and antiviral activity of poludan in suppositoria is potentiated by hyaluronic acid and antioxidants.

Cellular signalling and free-radical modulating activities of the novel peptidomimetic L-glutamyl-histamine.

A novel histamine-containing peptidomimetic, L-glutamyl-histamine (L-Glu-Hist), has been synthesized and characterized as a possible cytokine mimic which might lead to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure stabilize Fe2+-chelating complexes. L-Glu-Hist concentration-dependently accelerates a decrease in ferrous iron in ferrous sulfate solution and shows ferroxidase-like activity at concentrations less than 3 mM in the phenanthroline assay, whereas in the concentration range 3-20 mM it restricts the availability of Fe2+ to phenanthroline by chelation of iron ions.