Vaccination remains the only way to prevent tick-borne encephalitis (TBE). All TBE vaccines are based on strains of the Far Eastern and European subtypes of TBE virus. Currently, the Siberian subtype of the virus, which differs from the vaccine strains, accounts for 80–100% of the genetic population of TBE virus in most of Russia. The proportion of TBE vaccinated patients among those infected was different from year to year in Russia, e.g. 3.9% in 2012 and 1.5% in 2018, there were also some fatal cases registered among vaccinated patients. In this regard, evaluation of the effectiveness of vaccination against various genetic subtypes of TBE is a promising area of research. The purpose of this study was to summarise the results of studies investigating effectiveness of specific prevention of TBE as regards various genetic subtypes of the virus. The paper analyses data on the effectiveness of TBE vaccination in experimental settings and in real life. It was demonstrated that the use of vaccines for prevention of TBE is effective, provided the vaccination coverage is not less than 80%. The paper cites the data from a long-term study of the stability and protective activity of vaccine immunity against TBE virus strains isolated in highly endemic territories. It was established that TBE vaccines have high immunogenic activity and contribute to the production of stable protective antibodies against the strains of the three genetic subtypes of the virus. Protective efficacy of vaccination depends on the number of vaccinations received, the vaccination scheme, gender and age of those vaccinated. The paper concludes by saying that further studies are needed to assess TBE vaccine efficacy in order to improve vaccination tactics, to better understand causes of morbidity and mortality among vaccinated individuals.

Relevance. Vaccination against the tick-borne encephalitis (TBE), during the mass immunization, by using modern vaccines provides high epidemiological effect (98–99%); however, there are known cases of incidents among vaccinated population. The problem of incidents among vaccinated population is insufficiently studied, likewise a reliability of the diagnostic, vaccination conditions and causes of vaccinated people’s morbidity. Purpose of the article generalization of the information about morbidity among the vaccinated population. Conclusions. The review for the first time provides information about the main issues of this problem: the frequency of illness of vaccinated people in Russia (by federal districts and individual regions), disease development conditions, tied up with vaccination regimens and types of vaccines, clinical features and diagnosis of the disease of vaccinated people. Particular attention is paid to the state of post-vaccination immunity. The significance of two phenomena is being studied: incomplete neutralization of the virus, which leads to the formation of a fraction of a free infectious virus; and the phenomenon of the hyperimmunization with the development of immunological tolerance.

Currently available vaccines against tick-borne encephalitis (TBE) are highly effective; however, they do not ensure 100% protection. Laboratory diagnostics of TBE in vaccinated patients remains poorly developed. Objective. To compare the dynamics of humoral immunity in unvaccinated and vaccinated patients and to develop an algorithm of specific laboratory diagnostics of TBE. Patients and methods. We have tested 276 unvaccinated and 59 vaccinated patients using enzyme-linked immunosorbent assay for the detection of IgG and IgM against antigens of tick-borne encephalitis virus (TBEV). In hemagglutination inhibition assay, we used dry TBEV reagent. TBEV RNA was detected using reverse transcription polymerase chain reaction (RT-PCR). Results. We have identified three types of humoral immunity dynamics in vaccinated and unvaccinated patients: seroconversion, stable antibody titers, and negative (reverse) antibody dynamics with an at least 4-fold decrease in antibody levels. Among 39 vaccinated individuals, 18 patients demonstrated seroconversion, while 16 patients had stable antibody titers and 4 patients had negative dynamics. Patients with chronic TBE demonstrated different variants of humoral immunity dynamics. Discussion. We discuss the variants of antibody dynamics described above and diagnostic methods on the example of vaccinated patients. In individuals with stable antibody titers, we used an original method for detecting the dynamics of antibodies against Siberian strain of TBEV. Conclusion. In case of seroconversion, the level of specific immunity in vaccinated patients was higher than that in unvaccinated patients and healthy individuals vaccinated against TBE. Negative antibody dynamics is the rarest variant of humoral immunity development. The diagnosis of TBE in patients with stable antibody titers is confirmed by the detection of TBEV antigen, increasing serum levels of IgM, detection of TBEV RNA in the cerebrospinal fluid, and isolation of the virus. Keywords: vaccinated patients, humoral immunity, diagnosis, tick-borne encephalitis

A number of antibacterial drugs used for the treatment of combined viral and bacterial infections can cause immunosuppression, weighting of the acute course and activation of the persistent infection. Previously, it was found that among the antibacterial drugs, strong activators of persistent infection are streptomycin (group of aminoglycosides), cefamezin (group of cephalosporins), ristomycin (polypeptide antibiotic), the group of drugs that do not cause depression of humoral immunity includes gentamicin (aminoglycoside), kanamycin (aminoglycoside), levomycetin (synthetic antibacterial drug), florimycin (aminoglycoside). In this paper an experiment on Syrian hamsters shows the effect of using a new generation antibiotic — Ceftriaxone (beta-lactam antibiotic) on the course of acute tick-borne encephalitis.

Relevance.Modern inactivated culture vaccines against tick-borne encephalitis (TBE) with at least 70% of the population living in the natural foci of the FE give a high epidemiological effect. Unresolved issues are the simplification of the cumbersome vaccination scheme, the optimal number of revaccinations, the protective titer of antibodies against the Siberian subtype of the TBE virus dominant in Russia.Goalof this work is to study the state of postvaccinal immunity in the population of the highly endemic area of the Trans-Urals.Materials and methods. 1381 blood serum of the population vaccinated from 3 to 13 times with vaccines was studied: unconcentrated culture inactivated from strain No. 205 of the TBE virus produced by «Virion», Tomsk, «EnceVir» produced by «Microgen», Tomsk, produced by Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products of Russian.To identify specific antibodies – IgG, IgM, antigen of TBE virus, sets of reagents of ELISA from «Vector-Best» were used. Neutralizing activity of sera was determined by the index of neutralization index with 4 strains of the Siberian subtype of TBE virus.Results.The immune layer among the vaccinated population in 10 districts of the Kurgan region, which differ in epidemiological tension, ranges from 69.9% to 94.6%. The intensity of humoral immunity varied according to IgG titers in ELISA from 1: 100 – 1: 200 to 1: 3200 (rarely 1: 6400). The duration and intensity of immunity depends on the number of vaccinations and the number of missed remote revaccinations. Preservation and intensity of immunity with reliability P = 95%, higher in persons vaccinated 6–10 times compared with the group of vaccinated 3 times. In persons who had 4–8 booster dose of vaccine, the immunity persisted for 15–19–36 years with an IgG titer of not more than 1: 100. The neutralizing activity of the sera of vaccinated individuals with antibody titers from 1:100 to 1: 6400 was studied for the Siberian subtype of BCE. The degree of protection of the vaccinated population against the doses of the virus found in individual mites is determined. From the doses of the virus, 57% of the vaccinated population are most often found in mites, and from the dose of 105– 8%. Recommendations are proposed on the tactics of revaccination of the population, depending on the level of immunity.

The aim of this work is to study the rare clinical case of chronic tick-borne encephalitis (CHTBE), characterized by atypical course of infectious process, developing on intensive humoral immunity background. Materials and methods. The patient B., 50 years old, living in Kemerovo region, TBE endemic area. Was bitten by tick. The patient was twice vaccinated by: vaccine-TBE «EnceVir». The scheme of vaccination: between the first and second vaccinations – the interval is 16 days. Was hospitalized in the Kemerovo Regional Clinical Hospital with a diagnosis of Chronical form of TBE, mixed form (TBE and Ixodes tick-borne borreliosis). The immunological analysis was performed on TBE and ixodes tick-borne borreliosis was performed on ELISA assay. Results. The patient B, 50 years old serum was identified IgG antibodies, titer 1 : 1700 with a gradual decrease and stabilization from 1 : 800 to 1 : 600. IgM TBE antibodies were detected from the first days of the disease. TBE IgM were determined in titer from 1 : 600 to 1 : 3200 (5-fold increase of antibodies) in long-term observations. Throughout the infectious process, ixodes tick-borne borreliosis were not identified in the serum. In the neurological status was detected: a slight hypotrophy of the muscles of the first interdigital spaces, hypotrophy of shoulder girdle muscles, pain hypoesthesia at polyneuritis’s type. According to the results of the EMG study, the patient showed deceleration of excitation spread and neuropathy of the ulnar, median, peroneal and tibial nerves from both sides. According to MRI was detected the lack of accumulating contrast, presence of pathogenie pockets. The patient had no somatic symptoms of ixodes tick-borne borreliosis infection. Conclusion. The Diagnosis «Chronical TBE, polyneuritis form» based on the results of the EMG and ELISA studies in dynamic observations on the patient from 2016-2017.

Relevance.Тhe Ural Federal district (Ural Federal district) is a highly endemic tick-borne viral encephalitis (TBEV) territories in the Russian Federation. The epidemiological situation on the TBEV is studied in Sverdlovsk and Chelyabinsk regions and slightly shown in the Kurgan region. There is no information about the evolution TBEV, the structure of immunity population, vaccine prevention in the Kurgan region. The article presents the dynamics epidemiological situation on TBEV in the Kurgan region over a 30-year period.Materials and methods: Used expedition reports, viral encephalitis named after the Academy of medical Sciences of the USSR for 1983–2007, as well as materials of medical institutions of the Kurgan region 2007–2017. For population immunity used: hemagglutination test (HAI-test), neutralization test (NT). To identify specific antibodies – IgG, IgM, antigen of TBEV, sets of reagents of ELISA from «Vector-Best» were used. To immunotypicalli and genotypically Strains and isolates RNA of TBEV isolated in 1983–2007, used precipitation in agar (RDPA) and by RT-PCR technique in real time with genotypespecific probes.Results and discussions: Kurgan region is a highly TBEV endemic area. the morbidity rate – 18,3 per 100 thousand people 1983. Maximum elevation – 44.1 in 1996 to and decrease to 13.5 in 2000–2012. The immune part of the population according hemagglutination tests, on epidemiologically significant territories is 15–20%, (66% NT), in the regions with sporadic incidence is 8%, (21–50% NT), in non-endemic territories – 3%. At the present stage, the region marked the expansion of nosoareal TBEV due to the previously less significant Eastern regions. In Kurgan region vaccination coverage against TBE 39.3%. The clinical efficacy of vaccination was manifested in an increase in fever forms of TBE disease and a decrease in meningeal and focal forms of the disease. In the period 2004–2012 the number of vaccinated patients was 20.3% of the total number of patients.Сonclusions. Evolution of tick-borne encephalitis manifested the expansion of nosoareal TBEV, increase seasonal activity of ticks, the TBEV Siberian subtype is absolutely dominating.

Relevance. Modern inactivated culture vaccines against tick-borne encephalitis (TBE) with at least 70% of the population living in the  natural foci of the FE give a high epidemiological effect. Unresolved  issues are the simplification of the cumbersome vaccination scheme,  the optimal number of revaccinations, the protective titer of  antibodies against the Siberian subtype of the TBE virus dominant in Russia. Goal of this work is to study the state of postvaccinal immunity in the population of the highly endemic area of the Trans-Urals. Materials and methods . 1381 blood serum of the population vaccinated from 3 to 13 times with vaccines was studied: unconcentrated culture inactivated from strain No. 205 of the TBE  virus produced by «Virion», Tomsk, «EnceVir» produced by  «Microgen», Tomsk, produced by Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products of  Russian.To identify specific antibodies – IgG, IgM, antigen of TBE  virus, sets of reagents of ELISA from «Vector-Best» were used.  Neutralizing activity of sera was determined by the index of  neutralization index with 4 strains of the Siberian subtype of TBE  virus. Results. The immune layer among the vaccinated population in 10 districts of the Kurgan region, which differ in epidemiological tension, ranges from 69.9% to 94.6%. The intensity of humoral immunity  varied according to IgG titers in ELISA from 1: 100 – 1: 200 to 1:  3200 (rarely 1: 6400). The duration and intensity of immunity  depends on the number of vaccinations and the number of missed  remote revaccinations. Preservation and intensity of immunity with  reliability P = 95%, higher in persons vaccinated 6–10 times  compared with the group of vaccinated 3 times. In persons who had 4–8 booster dose of vaccine, the immunity persisted for 15–19–36 years with an IgG titer of not more than 1: 100. The neutralizing  activity of the sera of vaccinated individuals with antibody titers from 1:100 to 1: 6400 was studied for the Siberian subtype of BCE. The  degree of protection of the vaccinated population against the doses  of the virus found in individual mites is determined. From the doses  of the virus, 57% of the vaccinated population are most often found  in mites, and from the dose of 105– 8%. Recommendations are  proposed on the tactics of revaccination of the population, depending on the level of immunity.

The analysis of the use of the method for the evaluation of specific (immunogenic) activity of vaccines for preventing tick-borne encephalitis (TBE vaccines) against protective dilution (PD50) and the minimum immunizing dose (MID50) has been performed. The method was standardized and submitted to the regulatory documents for TBE vaccines authorized in the Russian Federation. When analyzing the results of the study of specific (immunogenic) activity of TBE vaccines (107 TBE vaccine batches by different manufacturers have been studied) it was confirmed that the choice of real lethal dose (RLD50) indicator of TBE virus (test strain «Absettarov») in the range of 100-3000 LD50, the reasonability of using BALB /c cell-line mice, the effectiveness of the national method of determining immunogenicity in terms of MlD50 for TBE vaccines authorized in the Russian Federation. The reasonability of using immunogenicity reference standard for TBE-OSO 42-28-48 to assess the reproducibility of the experiments, and the homogeneity of laboratory animals in terms of quality. Methods for determining TBE vaccine immunogenicity («specific activity (immunogenicity)» in terms of PD50 and MID50 is applicable both for Russian commercial TBE vaccines and for FSME-Immun vaccine, manufactured by «Baxter Vaccine AG», Austria.

The article presents the results of a long-term study of biological and genetic stability of tick-borne encephalitis strain 205 which is used by the FSUE «SPA «Microgen» to produce tick-borne encephalitis vaccines EnceVir (for adults) and EnceVir Neo for children, both of which are tissue cultured, inactivated, purified, and sorbed. The biological stability of strain 205 was studied at the seed lot stage using passages on outbred white mice: initial production strain 205 and production «stock strain». Lyophilisates of production seed lots were studied at different storage intervals at -20 °С (up to 9 years of storage and more). Biological activity parameters (tick-borne encephalitis virus (TBEV) titre in log LD50/ml) were studied by using different ways of infecting outbred white mice, and strain 205 identification (specificity) was determined by comparing it to a reference strain in a biological neutralization assay (BNA) according to the manufacturer’s specifications for the vaccines concerned. The same materials and a batch of TBEV vaccine produced from the production «stock strain» (lyophilisate of 1986) were analyzed by polymerase chain reaction (PCR) and sequencing for genetic stability during passaging and long-term storage. The results of the study made it possible to demonstrate the biological and genetic stability of strain 205 during production of TBEV vaccines.

The article presents the results of a long-term study of biological and genetic stability of tick-borne encephalitis strain 205 which is used by the FSUE «SPA «Microgen» to produce tick-borne encephalitis vaccines EnceVir (for adults) and EnceVir Neo for children, both of which are tissue cultured, inactivated, purified, and sorbed. The biological stability of strain 205 was studied at the seed lot stage using passages on outbred white mice: initial production strain 205 and production «stock strain». Lyophilisates of production seed lots were studied at different storage intervals at -20 °С (up to 9 years of storage and more). Biological activity parameters (tick-borne encephalitis virus (TBEV) titre in log LD 50 /ml) were studied by using different ways of infecting outbred white mice, and strain 205 identification (specificity) was determined by comparing it to a reference strain in a biological neutralization assay (BNA) according to the manufacturer’s specifications for the vaccines concerned. The same materials and a batch of TBEV vaccine produced from the production «stock strain» (lyophilisate of 1986) were analyzed by polymerase chain reaction (PCR) and sequencing for genetic stability during passaging and long-term storage. The results of the study made it possible to demonstrate the biological and genetic stability of strain 205 during production of TBEV vaccines.

The Chelyabinsk Region (Southern Urals) is high endemic territory. The TBE incidence is 3.57 ± 1.7 per 100 000 of population. A level of vaccination against TBE increased from 0.3 to 34.8% in 1999 - 2013. Specific immunity of population in 35.9% is connected with vaccination, in 64.1% with natural immunity consequently latent contact with TBE virus. Dynamics of vaccinal prevention, increasing of population immunity in different landscapes, and in different age groups were studied. 77.7% of TBE patients did not vaccinated, 18.2% received of specific immunoglobulin at postexposition and 3.7% persons were vaccinated. Unusual lethal case in patient, who received 8 doses of vaccine is analysed in this article.

Siberian subtype of TBE virus dominates in the most part of Russia outside of the Far East. Peculiarity of immunity induced by Siberian subtype during disease or inapparent infection and change of immunity after vaccination are described in this article. Protective titre of antibodies and persistence of TBE virus (TBEV) in vaccinated organism are discussed.

Tick-borne encephalitis (TBE) is a disease mainly affecting the central nervous system, serious medical and social problem in Russia and many European countries. TBE virus (TBEV) genetically divided into three major subtypes: the Far Eastern, European and Siberian. Siberian subtype of TBEV dominates in most part of Russia outside of the Far East. Modern cultural inactivated vaccine of domestic and foreign production prepared from the strains of the Far Eastern and European subtypes. In a review of the literature and our own researches are shown: the dominance of Siberian subtype (TBE) and data of vaccine-prevention. The importance of genetic differences between the Siberian subtype strains and vaccines strains are analyzed as well new approaches of the test strain selection.

Tick-borne encephalitis (TBE) is a disease mainly affecting the central nervous system, serious medical and social problem in Russia and many European countries. TBE virus (TBEV) genetically divided into three major subtypes: the Far Eastern, European and Siberian. Siberian subtype of TBEV dominates in most part of Russia outside of the Far East. Modern cultural inactivated vaccine of domestic and foreign production prepared from the strains of the Far Eastern and European subtypes. In a review of the literature and our own researches are shown: the dominance of Siberian subtype (TBE) and data of vaccine-prevention. The importance of genetic differences between the Siberian subtype strains and vaccines strains are analyzed as well new approaches of the test strain selection.

Chronic tick-borne encephalitis (CTBE) is a severe form of the disease, leading to permanent disability and death. Most cases of CTBE caused Siberian subtype of a virus of tick-borne encephalitis virus (TBEV), dominant in the Russian Federation. The pathogenesis of CTBE associated with persistence of TBEV in the central nervous system and the organs of the immune system. Specific vaccine therapy with using of inactivated full-virion vaccines prevents immunosuppression, leading to activation of persisting tick-borne encephalitis. The article describes various schemes of CTBE vaccinotherapy. Dynamics of humoral immunity in CTBE caused by Siberian subtype of TBEV. In the early stages and during remission antibodies against this subtype are detected. Vaccine therapy increases the level of immunity to all subtypes of TBEV, slowing the progression of the disease. In seronegative status of the patient vaccine therapy is not effective: from the central nervous system of a deceased patient severe strain «Zausaev» was isolated. Mechanisms of high immunity after 30-32 years after vaccine therapy and advantages of vaccine therapy compared with treatment of CTBE using specific immunoglobulin are discussed.