scholarly journals The Value of the Effect of the Level of Specific Antibodeis on Elimination Different Tick-Borne Encephalitis Virus Strains

2017 ◽  
Vol 16 (2) ◽  
pp. 50-54 ◽  
Author(s):  
G. N. Leonova ◽  
V. A. Lubova ◽  
A. V. Kalinin
Keyword(s):  
Virulent Strain ◽  
Highly Pathogenic ◽  
Tick Borne Encephalitis ◽  
Tbe Virus ◽  
Vaccine Prophylaxis ◽  
Tick Borne Encephalitis Virus ◽  
Different Strains ◽  
Virus Strains

We have shown the levels of specific antibodies that can neutralize different strains on the virulence of the virus of tick-borne encephalitis (TBE). Specific immunoglobulin with its titers of 1:100, 1:400 и 1:3200 and two TBEV strains with its doses 3 lg TCID50/ ml (Dal negorsk - highly pathogenic, Primorye-437 - not pathogenic for humans). Evidential basis of the activity of residual virus has been obtained in vitro and in vivo in 3, 24, 48 and 72 hours after infection cells of culture PK and mice neinbrednyh by the test samples. Immunoglobulin does not have a protective effect, if its titer is 1:100; inhibits low virulent strain (P-437), but not Dal negorsk one, if its titer is 1:400; and inhibits both strains, it its titer is 1:3200. Regarding the models of different TBE virus strains, this article suggests new approaches to studying the efficacy of specific vaccine prophylaxis and individual prescription of the amount and terms of revaccination for tick-borne encephalitis.

scholarly journals Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection In Vitro and in a Mouse Model

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
James Duehr ◽  
Silviana Lee ◽  
Gursewak Singh ◽  
Gregory A. Foster ◽  
David Krysztof ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dengue Virus ◽  
Human Plasma ◽  
Mouse Models ◽  
Zika Virus ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

ABSTRACT Recent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesis in vitro and in vivo in mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacity in vitro using K562 human myeloid cells expressing CD32 and in vivo using a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infection in vitro. A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromised Stat2−/− mice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement. IMPORTANCE The relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.

scholarly journals Phylogenetic analysis and distribution of far eastern tick-borne encephalitis virus subtype (Flaviridae, Flavirus, TBEV-FE) from Asia

2019 ◽  
Vol 64 (5) ◽  
pp. 250-256 ◽  
Author(s):  
G. N. Leonova ◽  
S. I. Belikov
Keyword(s):  
Molecular Genetic ◽  
Primorsky Krai ◽  
Khabarovsk Krai ◽  
Genetic Characteristics ◽  
Tick Borne Encephalitis ◽  
Tbe Virus ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern ◽  
Virus Strains ◽  
Virus Subtype

To date, a lot of data on molecular genetic characteristics of different tick-borne encephalitis virus strains has appeared. Only on the basis of the E protein genome, sequences of about 1,500 TBEV strains were registered in GenBank.The purpose of the work – revision and comparative analysis of data on complete genomes sequences of the Far Eastern subtype of TBE virus strains distributed in the Asian part of Eurasian continent.Material and methods. The data on the complete genomes of 84 strains of TBEV isolated in Asia were used; phylogenetic analysis was performed.Results and discussion: it was shown that variants of the TBEV of the Far Eastern subtype are circulating here and form three separate clusters (Sofjin, Senzhang- и Shkotovo-like strains). Sofjin strain (Sofjin-1953, Sofjin-Chumakov, Sofjin-KSY) was considered to be the reference for Far Eastern TBE virus subtype strains and a cluster of Sofjin-like strains. Sofjin-like strains were not found in China and Japan, but widely distributed throughout the area of Primorsky and Khabarovsk krai. The group of Senzhang-like strains was distributed in China, Eastern Siberia, Khabarovsk krai and northern Primorsky krai, but was not found in Japan (Hokkaido). According to molecular genetic characteristics the youngest and more genetically homogeneous group was the Shkotovo-like strains, isolated in the southern part of Primorsky krai, however not found on Hokkaido Island (Japan).Conclusion: revision of the complete genome characteristics of TBEV strains revealed the features of micro-evolutionary process of viral populations in the Asian part of Eurasia, show the individual affection of strains to certain territories, as well as detect random finds of such strains in the territories of other natural foci.

scholarly journals Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

2019 ◽  
Vol 9 (3-4) ◽  
pp. 559-567
Author(s):  
G. N. Leonova ◽  
O. S. Majstrovskaya ◽  
V. A. Lubova ◽  
N. B. Sanina
Keyword(s):  
Ex Vivo ◽  
Experimental Studies ◽  
Encephalitis Virus ◽  
Virus Elimination ◽  
Specific Antibodies ◽  
Tick Borne Encephalitis ◽  
Antibody Titers ◽  
Tick Borne Encephalitis Virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.

TBE in Bulgaria

2021 ◽  
Author(s):  
Iva Christova
Keyword(s):  
Virulent Strain ◽  
Goat Milk ◽  
Tick Borne Encephalitis ◽  
Antigenic Properties ◽  
Haemaphysalis Punctata ◽  
Tick Borne Encephalitis Virus ◽  
The 1960S ◽  
Virus Strains ◽  
European Subtype ◽  
Highly Virulent

First cases of probable tick-borne encephalitis (TBE) were reported in 1961 by Andonov et al. in eastern regions of Bulgaria.1 Possible TBE cases with the typical two-wave fever, originating from consumption of raw goat milk, were described back in 1953 by Vaptzarov et al. in southern Bulgaria.2 Investigations in the 1960s were able to isolate 3 tick-borne encephalitis virus (TBEV) strains from Haemaphysalis punctata and 1 from Dermacentor marginatus ticks from goats and sheep in the district of Plovdiv.3 The antigenic properties of these 4 virus strains were identical to the highly virulent strain “Hypr” of the European subtype of TBEV (TBEV-EU).

Effect of immature tick-borne encephalitis virus particles on antiviral activity of 5-aminoisoxazole-3-carboxylic acid adamantylmethyl esters

2021 ◽  
Vol 102 (9) ◽  
Author(s):  
Ksenia K. Tuchynskaya ◽  
Anastasiia D. Fomina ◽  
Nikolai A. Nikitin ◽  
Viktoria V. Illarionova ◽  
Viktor P. Volok ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Antiviral Activity ◽  
Severe Disease ◽  
Experimental Studies ◽  
Encephalitis Virus ◽  
Viral Population ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is common in Europe and Asia and causes a severe disease of the central nervous system. A promising approach in the development of therapy for TBEV infection is the search for small molecule antivirals targeting the flavivirus envelope protein E, particularly its β-n-octyl-d-glucoside binding pocket (β-OG pocket). However, experimental studies of candidate antivirals may be complicated by varying amounts and different forms of the protein E in the virus samples. Viral particles with different conformations and arrangements of the protein E are produced during the replication cycle of flaviviruses, including mature, partially mature, and immature forms, as well as subviral particles lacking genomic RNA. The immature forms are known to be abundant in the viral population. We obtained immature virion preparations of TBEV, characterized them by RT-qPCR, and assessed in vivo and in vitro infectivity of the residual mature virions in the immature virus samples. Analysis of the β-OG pocket structure on the immature virions confirmed the possibility of binding of adamantylmethyl esters of 5-aminoisoxazole-3-carboxylic acid in the pocket. We demonstrated that the antiviral activity of these compounds in plaque reduction assay is significantly reduced in the presence of immature TBEV particles.

TBE in Bulgaria

2020 ◽  
Keyword(s):  
Virulent Strain ◽  
Goat Milk ◽  
Tick Borne Encephalitis ◽  
Antigenic Properties ◽  
Haemaphysalis Punctata ◽  
Tick Borne Encephalitis Virus ◽  
The 1960S ◽  
Virus Strains ◽  
European Subtype ◽  
Highly Virulent

First cases of probable tick-borne encephalitis (TBE) were reported in 1961 by Andonov et al. in eastern regions of Bulgaria.1 Possible TBE cases with the typical biphasic course, originating from consumption of raw goat milk, were described back in 1953 by Vaptzarov et al. in southern Bulgaria.2 Investigations in the 1960s were able to isolate 3 tick-borne encephalitis virus (TBEV) strains from Haemaphysalis punctata and 1 from Dermatocentor marginatus ticks from goats and sheep in the district of Plovdiv.3 The antigenic properties of these 4 virus strains were identical to the highly virulent strain “Hypr” of the European subtype of TBEV (TBEV-EU).3

Inhibition of Tick-Borne Encephalitis Virus Replication with Eprosartan and Ribavirin In Vitro and In Vivo

2020 ◽  
Vol 65 (9-10) ◽  
pp. 8-12
Author(s):  
G. N. Leonova ◽  
O. S. Maistrovskaya ◽  
V. A. Lubova
Keyword(s):  
Life Expectancy ◽  
Treatment Regimen ◽  
Active Agent ◽  
Encephalitis Virus ◽  
In Vivo Model ◽  
Control Group ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Active search for new antiviral substances is currently underway. The purpose of this work is to identify the inhibitory activity of eprosartan medication in comparison with ribavirin in vitro and in vivo in relation to tick-borne encephalitis virus. The value of the half the maximum cytotoxic concentration (CC50) for eprosartan (8.8±1.2 mg/ml) and ribavirin (1.074±0.16 mg/ml) was established. To obtain a medium effective virus-inhibiting concentration (IC50) of the medications, EIA data were used. Using nonlinear regression analysis of the percentage of antigen positive samples, IC50 values of the studied substances were obtained, which for eprosartan was 0.64±0.23 mg/ml in the treatment regimen. The selective index (SI) or chemotherapeutic index (CTI) was 13.7. The IC50 of ribavirin was 0.0067±0.0015 mg/ml, SI or CTI was 160. The suppression of viral reproduction 2.0 log TCID50 occurred in PEK cell culture under the influence of eprosartan at concentrations of 1.2–3.0 mg/ml (treatment regimen), under the influence of ribavirin — 0.2 mg/ml (prophylactic regimen) and 0.2–0.0125 mg/ml (treatment regimen). Samples with eprosartan (1.5 and 0.6 mg/ml) showed an increase in survival of mice by 50% and 20% compared with the virus control group in the in vivo model and, accordingly, an increase in average life expectancy of 5.2 and 2.1 days. Samples with ribavirin (0.05 and 0.025 mg/ml) increased the survival of mice by 60% and 40% and, accordingly, increased the life expectancy by 7.3 and 4.8 days. The data obtained allow recommending eprosartan as an active agent against tick-borne encephalitis virus along with ribavirin.

scholarly journals Tick populations from endemic and non-endemic areas in Germany show differential susceptibility to TBEV

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katrin Liebig ◽  
Mathias Boelke ◽  
Domenic Grund ◽  
Sabine Schicht ◽  
Andrea Springer ◽  
...  
Keyword(s):  
Differential Susceptibility ◽  
Feeding Rates ◽  
Infection Rates ◽  
Lower Saxony ◽  
Tick Borne Encephalitis ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
In Vitro Feeding ◽  
Tbev Infection

Abstract Tick-borne encephalitis virus (TBEV) is endemic in twenty-seven European countries, transmitted via the bite of an infected tick. TBEV is the causative agent of one of the most important viral diseases of the central nervous system (CNS). In Germany, 890 human cases were registered between the years 2018–2019. The castor bean tick, Ixodes ricinus, is the TBEV vector with the highest importance in Central Europe, including Germany. Despite the nationwide distribution of this tick species, risk areas of TBEV are largely located in Southern Germany. To increase our understanding of TBEV-tick interactions, we collected ticks from different areas within Germany (Haselmühl/Bavaria, Hanover/Lower Saxony) and infected them via an in vitro feeding system. A TBEV isolate was obtained from an endemic focus in Haselmühl. In two experimental series conducted in 2018 and 2019, ticks sampled in Haselmühl (TBEV focus) showed higher artificial feeding rates, as well as higher TBEV infections rates than ticks from the non-endemic area (Hanover). Other than the tick origin, year and month of the infection experiment as well as co-infection with Borrelia spp., had a significant impact on TBEV Haselmühl infection rates. Taken together, these findings suggest that a specific adaptation of the tick populations to their respective TBEV virus isolates or vice versa, leads to higher TBEV infection rates in those ticks. Furthermore, co-infection with other tick-borne pathogens such as Borrelia spp. can lower TBEV infection rates in specific populations.

scholarly journals Probing the Flavivirus Membrane Fusion Mechanism by Using Monoclonal Antibodies

2007 ◽  
Vol 81 (20) ◽  
pp. 11526-11531 ◽  
Author(s):  
Karin Stiasny ◽  
Samantha Brandler ◽  
Christian Kössl ◽  
Franz X. Heinz
Keyword(s):  
Monoclonal Antibodies ◽  
Fusion Protein ◽  
Binding Sites ◽  
Fusion Inhibition ◽  
Tick Borne Encephalitis ◽  
Target Membrane ◽  
Initial Interaction ◽  
Tick Borne Encephalitis Virus ◽  
Late Stages

ABSTRACT In this study, we investigated in a flavivirus model (tick-borne encephalitis virus) the mechanisms of fusion inhibition by monoclonal antibodies directed to the different domains of the fusion protein (E) and to different sites within each of the domains by using in vitro fusion assays. Our data indicate that, depending on the location of their binding sites, the monoclonal antibodies impaired early or late stages of the fusion process, by blocking the initial interaction with the target membrane or by interfering with the proper formation of the postfusion structure of E, respectively. These data provide new insights into the mechanisms of flavivirus fusion inhibition by antibodies and their possible contribution to virus neutralization.

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