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A study was undertaken to prove that a vaccine drug based on the fast-growing MB-7 (MB-7 VD) of hepatitis A virus (HAV) is safe. It was established that MB-7 VD, when once injected to white outbred mice and when 4 times injected to Hartley guineas pigs, did not cause any hematological and biochemical changes in the peripheral blood or in the condition of the central nervous system of experimental animals, which shows that MB-7 VD is free of any toxic properties.

The influence of a vaccine based on the MB-7 strain of hepatitis A virus (VP-MB-7) designed at the "Vector" Center of Virology and Biotechnology was studied. VP-MB-7 was found to provoke no allergic response and to have an activating effect on the specific and non-specific responses of cell and humoral immunity similar to those evoked by hepatitis A vaccine "Hep-A-in Vac".

This paper sums up the results of controlled field clinical trials of adult and childhood variants of Harvix, inactivated vaccine from hepatitis A. The vaccine is weakly reactogenic and safe. After a single injection of Harvix-1440 vaccine to adults the percentage of seroconversions in previously seronegative individuals was 80.6%, with the mean geometrical antibody titer 119 mIU/ml. In children aged 3-10 years the percentage of seroconversions after a single injection of Harvix-720 vaccine was 100%, the mean geometrical of antibody titer being 427 mIU/ml. Results of laboratory control and field clinical trials recommend both variants of Harvix vaccine for prevention of hepatitis A in the Russian Federation.

New monoclonal antibodies (MAbs) to adenovirus hexon, highly active in ELISA and immunofluorescent analysis, were prepared. According to competitive ELISA, new MAbs differed in their blocking activity and were directed to 2 different hexon epitopes. MAb 3H8 did not modify antigen binding of the rest MAbs labeled with peroxidase (PAb x Pox), and none of unlabeled MAbs suppressed the reaction of MAb x Pox 3H8. MAbs 1E8 7F1, 1E11, and 3B1 reacted with each other but differed by the spectrum and level of competitive inhibition, which indicated that they were directed to different epitopes of adenovirus hexon. Comparison of the specific activity of MAbs 7F1 and 1E8 in direct immunofluorescent detection of adenovirus antigens in infected cell cultures and clinical materials from patients showed a good coincidence (90-97%) of the results with the IMAGEN Adenovirus test (Dako) and with polyclonal FITC conjugates to adenovirus hexon.

Commercial inactivated culture polyvaccine against herpes simplex viruses (types 1 and 2) developed at D. I. Ivanovsky Institute of Virology promoted cessation of viremia. During the first vaccination viremia coincided with appearance of a focal allergic test on the retina, which is proposed for the diagnosis of herpetic involvement of the posterior compartment of the eye. T-cellular immunity normalized after a course of vaccination. Experimental immunization of rats and vaccination of patients with chronic ophthalmic and genital herpes demonstrated the therapeutic activity of inactivated herpetic polyvaccine in suppositoria.

Russian cultural concentrated inactivated vaccine protecting from hepatitis A--Hep-A-in-vac was used for immunization of children. The vaccine is slightly reactogenic and completely safe in children aged 3-17 years vaccinated twice in a dose of 0.25 ml. Double immunization of seronegative children with a 1-month interval led to conversion in 89.7% children. In 64.1% children titers of antibodies to hepatitis A virus reached 20 mIU/ml and higher, which indicates rather high antigenic activity of the vaccine.

Central retinal vein occlusion is one of the most frequently encountered vascular affections of the retina. In spite of this its management is still a matter of debate. Histopathological findings have prompted us to conduct a study in patients presenting with central retinal vein occlusion (n = 63). Exposure to plasmapheresis as treatment of the above condition (1 to 3 sessions) resulted in a significant retardation of erythrocyte aggregation, decrease in fibrinogen concentration, and in the hematocrit value, and a prolongation of activated thromboplastin time. The results obtained suggest that plasmapheresis can be recommended for use in the treatment of central retinal vein occlusion.

A universal mathematical approach (algorithm) to assessment of the efficacy of new preparations for the diagnosis of rotavirus infection, analysis and processing of the results involves assessment of the detection rate of infection, specificity of preparations, probability of positive and negative diagnoses, total index of coincidence of results of diagnosis with the reference method, and chi 2 and phi2 coefficients indicating the reliability of relation to the reference method and the strength of this relation. Diatest software is proposed for accelerating statistical processing of the results. Use of the algorithm and software permits assessing the efficacy of diagnostic agents for rotavirus and other infections.

The results of the study of the reactogenicity, safety and immunological activity of Russian cultural vaccine against hepatitis A are presented. The vaccine was found to have specific safety, moderate reactogenicity and pronounced immunological activity. In addition, the study of the prophylactic efficiency of the vaccine in the pre-epidemic period of the outbreak of hepatitis A morbidity in a group exceeding 14,000 adults was carried out. The study revealed high prophylactic efficiency of the vaccine (its efficiency rate was equal to 97.7%). On the basis of materials thus obtained vaccine "Hep-A-in-Vac" was recommended for use in medical practice for the prophylaxis of hepatitis A among adults.

In the past 5 years, the investigators of the "VECTOR" SRB VB and the L.A. Tarasevich State Institute of Standardization and Control of Medical Biological Preparations have jointly designed sera reference panels containing anti-HIV-1 IgG, anti-HCV IgG, and anti-HAV IgM which have been approved as national standard panels. The panels are intended for use in controlling the specificity and stability of the most widely used ELISA diagnostic kits and immunoblot test systems during production, control, and application stages. Some problems of development and production of these panels, including the representation of different sera in the panels and the selection of specific IgG concentrations in the different sera in the panel are described. The authors also attract attention to the stabilization of the specific characteristics of panel sera during storage and transportation.

Comparative analysis of the specific activities of various batches of Hep-A-in-Vac vaccine showed that the immunologic efficacy of the agent directly depended on the content of hepatitis A virus antigen in the vaccine dose. The results of studying the immunogenicity of the agent on volunteers are compatible with the results of experimental studies and indicate that the test of guinea pigs adequately assesses this characteristic. Assessment of the immunogenic properties of Hep-A-in-Vac prepared using improved technology indicates that Russian vaccine injected three times in a dose containing at least 40 U EIA ensures 87.5% seroconversion in adult seronegative volunteers with the mean geometrical titer of antibodies to hepatitis A virus equal to 683 mIU/ml.

Modernization of the protocol and optimization of the technology of preparation of inactivated hepatitis A vaccine helped prepare the experimental lots of inactivated vaccine meeting all the requirements to such preparations and the WHO recommendations.

Clinical trials of inactivated hepatitis A vaccine Hep-A-in-Vac demonstrated its specific safety and moderate reactogenicity, manifesting by short-term fibrillar twitching of musculus deltoideus at the site of injection. After a course of three immunizations 87.5% seronegative vaccines developed a high level of specific antibodies to hepatitis A virus with at least 100 reverse values of titers. In controls antibody titers remained seronegative in 90% cases. These data indicate evident immunologic activity of Hep-A-in-Vac vaccine.

The parameters of plasma-platelet component of hemostasis were studied by autocoagulation test in 90 patients with rheumatoid arthritis of varying activity. To specify the role of blood platelets, their counts were estimated, as was their functional activity. Plasma coagulating activity was found elevated and anticoagulating activity reduced in disease of the first and second degrees of activity, particularly so in the second degree. In patients with the third activity degree these parameters are within the normal range. The platelets augment hypercoagulation signs and reduce plasma anticoagulation potential in disease of the third degree of activity most of all. This leads to augmentation of thrombophilia signs, thus creating favorable conditions for intravascular coagulation and formation of microthrombi, which may eventually result in aggravation of rheumatoid synovitis and development of visceritis.

A fast-growing cytopathic isolate of human hepatitis A virus (strain MB-7) was derived from fecal samples of infected patients and adapted to growth in FRhK-4 cell culture. A positive serum standard against HAV and electron microscopy were used to demonstrate that MB-7 belonged to human hepatitis A virus. The strain MB-7 induced plaque formation in FRhK-4 under agar overlay after 10-12 days of incubation. The PCR products of gene VP1 were cloned in E. coli and its primary structure was determined. MB-7 was shown to have more homology with HAV strains isolated in the USA and China.

Lowered, as compared to the normal, coagulation activity of hemolyzed and intact red blood cells was recorded in rheumatic fever patients with minimal activity of the process in the presence of hypercoagulation syndrome detectable in the plasma. This activity is low-dependent on the degree of chronic circulatory insufficiency (CCI), and has a tendency to further lowering but not rising under the effect of the treatment conducted. Aggregation activity of red blood cells in patients with CCI of 0-I degree is lowered, in those with CCI of IIA and IIB-III degree--elevated, and it is highest in patients with CCI of IIB-III degree. Fibrinolytic activity of red blood cells recorded in normal subjects is lost in all the groups of patients, regardless of the observation period, with appearance or elevation of fibrinolysis inhibitors in them. Erythrocytic hemostasis alterations detected at varying stages of the course and treatment of rheumatic fever may be conducive to the reduction or growth of overall plasma-erythrocytic coagulation potential thrombophilia.

The results of the controlled field trial of lyophilized erythrocytic immunoglobulin diagnosticum for the detection of hepatitis A virus antigen in the urine and feces of patients are presented. This diagnosticum was used for the study of urine and fecal samples from 225 patients (of these, 176 had hepatitis A) and 54 healthy persons in the passive hemagglutination (PHA) test. Their blood sera were studied in the PHA test (to detect HBsAg) and the radioimmunoassay (to detect anti-HAV IgM). The immunoglobulin diagnosticum under study was found to be nonspecific and faintly sensitive and, therefore, unsuitable for use in medical practice.

The diagnostic value of the first experimental production batches of assay kit "DIAGN-A-HEP", produced at the Institute of Poliomyelitis and Viral Encephalitides (USSR Acad. Med. Sci.) and intended for the determination of IgM to hepatitis A virus (HAV) in the enzyme immunoassay (EIA), has been studied in comparison with that of the internationally known and widely approved commercial EIA system "HAVAB-MEIA" for the determination of antibodies to HAV (the product of Abbott, USA). The study has revealed that the EIA kit "DIAGN-A-HEP" is highly sensitive and specific, and the diagnostic value of this kit is not inferior to that of the commercial assay system "HAVAB-MEIA". On the basis of this study the use of the EIA kits "DIAGN-A-HEP" in medical practice has been allowed by the decree of the Ministry of Health of the USSR.

Complex treatment with direct and indirect anticoagulants and deaggregants carried out in 41 patients with dilated cardiomyopathy produces a significant positive effect on the condition of plasma hemostasis allowing to control the signs of hypercoagulation changes of the general coagulation, fibrinogen-like and antiheparin activity leading to normalization of fibrinolysis of the euglobulin plasma fraction. Prolonged intake of indirect anticoagulants furthers reduction of development of thromboembolism by 12.1%.

Immunological memory has been demonstrated in lymphocytes of persons vaccinated against tick-borne encephalitis (TBE). Stimulation indices (SI) of lymphocytes in response to TBE virus antigens in lymphocyte blast transformation test increased after complete vaccination course with the commercial vaccine; by this time, sera of vaccinees contained virus neutralizing antibodies. The concentrated purified vaccine had a higher immunogenic activity, as evidenced by increased SI and virus neutralizing antibodies (NA) in the vaccinated subjects already after the first and second vaccinations.

Most arbovirus infections are characterized by multiplication of the causative agent in tissues of the reticuloendothelial system. In this study, the effect of some viruses of the tick-borne encephalitis complex on the reaction of B-cells of mouse spleens was investigated by the hemolysin-producing activity (number of plaque-forming cells). To equal small doses of a highly virulent (Pan), naturally attenuated (Tp-21) and experimentally attenuated (Tp-21-237) strains the immunocompetent cells of mouse spleens responded by active reactions. The immunocompetence of these cells after primary introduction of the antigens persists and revaccination response occurs after a secondary infection with the same viruses. Under these experimental conditions the active response of spleen cells to the antigenic stimulation correlates with formation of the specific resistance and does not correlate with the level of antihemagglutinins in the blood.

Patients with dermal and genital forms of recurring herpes were found to have decreased levels of leukocytes and changed balance of the peripheral blood lymphocyte populations. Treatment with herpes inactivated cultural polyvaccine produced a therapeutic effect in a significant number of patients which was accompanied by a correcting effect of the vaccine on their immune status.

Heterogeneity of antibodies against influenza virus hemagglutinin has been confirmed. Various subpopulations of antibodies to the A/Khabarovsk/15/76 hemagglutinin were demonstrated some of which showed greater affinity to MRC-11 hemagglutinin than to the HA of the strain inducing this antibody synthesis. Apparently subpopulations of antibodies with low affinity to their "own" epitopes in the hemagglutinin-immunogen may develop which, however, may show a sufficiently high affinity to these epitopes in hemagglutinins of other strains.

Certain parameters of humoral and cellular immunity induced by attenuated tick-borne encephalitis (TBE) and Langat virus strains were studied in monkeys. The immunogenic activity of the strains inoculated subcutaneously and intracerebrally was manifested by two processes: synthesis of specific antibody and cellular immune response. The highest titers of humoral immunity in N, HI, and CF tests were observed to homologous viruses. The immune response to both homologous and heterologous viruses could be optimized by increasing the number of antigenic stimulations. The sequence of antibody synthesis of the macro- and microglobulin series was similar in monkeys infected with virulent and attenuated strains. Cellular immunity reactions were detected and changes in the quantity and functional activity of T- and B-lymphocytes were determined. Most marked immunological changes were observed with the virulent TBE virus strain as compared with naturally and experimentally attenuated Langat virus strains.

A long-term viremia (12 days postinoculation, the observation period) of both cellular and plasma type was detected in mice experimentally infected with tick-borne encephalitis virus, the Sophyin strain. Preliminary vaccination was found to prevent viremia in experimentally infected animals. Comparative studies of cellular and humoral immune responses in vaccinated mice showed the cellular immune responses to be most important in eliminating the virus upon subsequent experimental inoculation of mice with tick-borne encephalitis virus.

Live influenza vaccines prepared from influenza virus strains H/32/5 (H1N1) and H/1/2/17 (H3N2) induce the formation of humoral immunity only in a part of the vaccinees and cause the transitory quantitative deficiency of T-lymphocytes in their blood, resulting in the poorly pronounced booster effect of the subsequent revaccination.

Inactivated whole-virion and split-virion influenza vaccines adsorbed on aluminium hydroxide did not suppress the immune system of the vaccinees. Immunization with these vaccine preparations induced the formation of both cell-mediated and humoral immunity in over 60% of the vaccinees.

The results of the trials of dried erythrocyte immunoglobulin immunodiagnosticum for the detection of hepatitis A virus antigen, developed by a group of scientists at the Tashkent Research Institute for Vaccines and Sera, are presented. The immunodiagnosticum is specific to hepatitis A virus antigen and suitable for the detection of this antigen in fecal and urine samples from patients with viral hepatitis A in the acute stage of the disease.

Inactivated vaccines against tick-borne encephalitis, concentrated by ultracentrifugation and unconcentrated, stimulate both the T- (an increase in the proportion of the active subpopulation of T-lymphocytes) and B-cell (an increase in the percentage of EAC+-rosette-forming cells) immunity in the vaccines, the concentrated vaccine being more active.

The indices of cellular and humoral immunity (the number of leukocytes, lymphocytes, T- and B cells, E- and EAC-RFC, blastogenic reaction of lymphocytes in response to treatment with phytohemagglutinin and influenza virus antigen in vitro, antihemagglutinin and influenza virus antigen in vitro, antihemmagglutinin titres) in humans vaccinated with different types of inactivated influenza vaccines produced in the USSR and the GDR were investigated. The immunogenic potency, general and immunological innocuity of the inactivated influenza vaccines under study and more marked stimulation of the B-system of immunity by them were demonstrated.

Inactivated concentrated and unconcentrated vaccines against tick-borne encephalitis given to 80 normal subjects produced no suppressing effect on the quantitative values of the immune status. Immunogenesis was characterized by stimulation of both T- and B-links of the immune system of the vaccines. With the unconcentrated vaccine a greater response was demonstrated after 3 injections; the concentrated vaccine induced an intensive immune response after 2 injections.

The indices of blast transformation of lymphocytes to polyclonal mitogens of phytohemagglutinin (PHA) and Pokeweed mitogen (PWM) and to tick-borne encephalitis virus antigen (TBE) were studied in 80 individuals in the course of vaccination against tick-borne encephalitis. In the time course of vaccination reactions of blast transformation of lymphocytes was found to decrease to PHA and to increase to TBE and PWM antigens; spontaneous blast transformation also increased. Increased blast transformation reaction to TBE and PWM antigen correlated with the results of serological studies.

Quantitative characteristics of the process of solubilization of influenza H1N1 and H3N2 virus hemagglutinin treated with bromeline enzyme were studied. After a long-time contact of viruses with the enzyme the hemagglutinin was found to be destroyed significantly. Certain conditions should be observed in order to increase the amount of hemagglutinin separated by the enzyme and its final yield. First, the quality of the original virus concentrate should be evaluated by electron microscopy. Second, the process of hemagglutinin solubilization should be monitored by single radial immunodiffusion method and electron microscopy to determine the optimal period of incubation of the virus material with bromeline. Finally, several (usually 2-3) incubations of optimal duration ("fractionated" incubation) should be carried out.

The main indices of the coagulogram, fibrinolysis and adhesive-aggregational properties of thrombocytes were evaluated in 40 patients with dilated cardiomyopathy with the purpose of determining the pathogenetic factors of thrombogenesis. Hypo- and hypercoagulation changes were found as well a reduction of the number of thrombocytes while the adhesiveness index remained unchanged; the aggregation and deaggregation capacities of thrombocytes reduced, the general fibrinolytic plasma activity increased.

Antigenic relationships of the vaccine A/Victoria/35/72 strain and vaccine candidate A/Khabarovsk/15/76 and recombinant RK-5 strains with hemagglutinins of the epidemic A/Victoria/3/75, A/Leningrad/173/75, and A/Victoria/112/76 strains were studied by radioimmunoassay (RIA) in two test systems. Alongside with other tests RIA is useful and expedient for rapid and accurate quantitative evaluation of the antigenic conformity of influenza virus strains under comparison.

The level and dynamics of lymphocyte blastogenesis in response to phytohaemagglutinin (PHA) and to specific influenza virus antigen were studied in 3 groups of humans, vaccinated with live or inactivated whole virion influenza vaccines (H3N2 type) and placebo (control group). Both live and inactivated influenza vaccines did not change significantly the functional activity of T lymphocytes as determined by the mean values of stimulation index (SI). The analysis of individual values of PHA-dependent blastogenic response, however, revealed a decrease in SI as compared with its prevaccination level in 33.3 +/- 11.4% of the vaccinees given the live influenza vaccine.

The functional activity of lymphocytes of patients with severe forms of recurrent cutaneous-genital herpes was studied in the course of treatment with inactivated polyvalent herpes vaccine on the basis of lymphocyte blast-transformation response to polyclonal mitogens and herpes simplex virus antigen. In the group of patients who showed a marked therapeutic effect as a result of the treatment the initially high values of the antigen-dependent lymphocyte blast-transformation test declined and became normal. Thus, in some cases the herpes vaccine exerts an immunomodulating effect normalizing the functions of different lymphocyte subpopulations.