scholarly journals Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and May Elicit NS1-Specific Antibody Responses in Vaccinated Individuals

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 81 ◽  
Author(s):  
Jiri Salat ◽  
Kamil Mikulasek ◽  
Osmany Larralde ◽  
Petra Pokorna Formanova ◽  
Ales Chrdle ◽  
...  
Keyword(s):  
Viral Envelope ◽  
Structural Protein ◽  
Specific Antibodies ◽  
Virus Challenge ◽  
Ms Analysis ◽  
Tick Borne Encephalitis ◽  
Ns1 Antigen ◽  
The Mean ◽  
Tick Borne Encephalitis Virus ◽  
Viral Surface

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, namely FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific Western blot analysis also detected anti-NS1 antibodies in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

scholarly journals Tick-borne Encephalitis Virus Vaccines Contain Non-structural Protein 1 (NS1) Antigen and May Elicit NS1-Specific Antibody Responses in Vaccinated Individuals

2020 ◽  
Author(s):  
Jiri Salat ◽  
Kamil Mikulasek ◽  
Osmany Larralde ◽  
Petra Pokorna Formanova ◽  
Ales Chrdle ◽  
...  
Keyword(s):  
Viral Envelope ◽  
Structural Protein ◽  
Specific Antibodies ◽  
Virus Challenge ◽  
Ms Analysis ◽  
Tick Borne Encephalitis ◽  
Ns1 Antigen ◽  
The Mean ◽  
Tick Borne Encephalitis Virus ◽  
Viral Surface

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN&reg; (Pfizer) and Encepur&reg; (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received &le;3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p &lt; 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

scholarly journals CHARACTERISTICS OF THE FAR EASTERN POPULATION OF TICK-BORNE ENCEPHALITIS VIRUS AND SOLVING ISSUES OF SPECIFIC PREVENTION

2018 ◽  
Vol 3 (4) ◽  
pp. 42-46
Author(s):  
G. N. Leonova
Keyword(s):  
Virulent Strain ◽  
Biological Properties ◽  
Encephalitis Virus ◽  
Viral Population ◽  
Full Genome Sequencing ◽  
Genetic Characteristics ◽  
Specific Antibodies ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

The subdivision of the viral population into subtypes and clusters based on the molecular genetic characteristics of the tick-borne  encephalitis virus (TBEV) strains predetermines not only the  differences in the biological properties of these strains, but also their different responses to specific antibodies in persons vaccinated against TBE.The aim of the present study is to show the differences in biological properties on the model of two strains of Far Eastern TBEV subtype  belonging to different clusters and to substantiate the need for a  personalized approach to the vaccine prophylaxis of tick-borne encephalitis.Results. Two strains of TBEV were used in the studies. On the basis of full genome sequencing the Dal’negorsk strain (FJ402886,  GenBank) is referred to the typical representative of Sofjin-like, and  Primorye-437 (JQ825162, GenBank) – to Oshima-like TBEV strains  of the Far Eastern subtype.The experiment shows the levels of  specific antibodies capable of neutralizing virulence strains of tick- borne encephalitis virus. Low antibody titers (1:100 and 1:400) can  neutralize only a low dose of a non-virulent strain of tick-borne  encephalitis virus. Reliable protection against the disease of people infected with virulent strains of the TBEV can provide only a  high level of specific antibodies.Conclusion. If the level of specific antibodies of IgG is 1:400 or lower, the vaccination course should be continued, at a titer of  antibodies above 1:400, revaccination can be postponed subject to  annual monitoring of specific immunity parameters in the pre-epidemic TBE season.

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.

scholarly journals The Red Fox (Vulpes vulpes) as Sentinel for Tick-Borne Encephalitis Virus in Endemic and Non-Endemic Areas

2020 ◽  
Vol 8 (11) ◽  
pp. 1817
Author(s):  
Maja Haut ◽  
Philipp Girl ◽  
Beate Oswald ◽  
Thomas Romig ◽  
Anna Obiegala ◽  
...  
Keyword(s):  
Vulpes Vulpes ◽  
Red Fox ◽  
Surrogate Marker ◽  
Published Data ◽  
Notifiable Disease ◽  
Red Foxes ◽  
Specific Antibodies ◽  
Tick Borne Encephalitis ◽  
Risk Areas ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis caused by a neurotropic arbovirus (TBEV). In Germany, TBE is classified as a notifiable disease with an average of 350 autochthonous human cases annually. The incidence-based risk assessment in Germany came under criticism because every year, a number of autochthonous human TBE cases have been detected outside of the official risk areas. Therefore, it is necessary to find additional parameters to strengthen TBEV surveillance. The aim of this study was to examine red foxes as sentinels for TBE. Thus far, there are no published data about the sensitivity and specificity for serological methods testing fox samples. Hence, we aimed to define a system for the screening of TBEV-specific antibodies in red foxes. A total of 1233 fox sera were collected and examined by ELISA and IIFA and confirmed by micro-NT. The overall seroprevalence of antibodies against TBEV in red foxes from Germany confirmed by micro-NT was 21.1%. The seroprevalence differed significantly between risk (30.5%) and non-risk areas (13.1%), with good correlations to local TBE incidence in humans. In conclusion, serological monitoring of red foxes represents a promising surrogate marker system and may even determine unexpected TBEV foci in regions currently regarded as non-risk areas.

scholarly journals Glucagon-like peptide-2 receptor is a receptor for tick-borne encephalitis virus to infect nerve cells

2021 ◽  
Author(s):  
Xinwen Chen ◽  
Qi Yang ◽  
Jizheng Chen ◽  
Rongjuan Pei ◽  
Yun Wang ◽  
...  
Keyword(s):  
Nerve Cells ◽  
Encephalitis Virus ◽  
Viral Envelope ◽  
Infectious Dose ◽  
Tick Borne Encephalitis ◽  
A Genome ◽  
Glucagon Like Peptide ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection ◽  
Deficient Mice

Abstract Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that causes severe encephalitis disease1,2. Host proteins required for TBEV entry remain largely unknown3. Here we performed a genome-wide CRISPR-Cas9 knockout screen and identified G-protein-coupled receptor glucagon-like peptide-2 receptor (GLP2R) as a receptor for TBEV to infect nerve cells. Knockdown or knockout of GLP2R reduced TBEV infection of different nerve cells; trans supply of GLP2R restored viral infection. GLP2R directly binds to viral envelope domain III through its extracellular loop 1 (ECL1). TBEV infection can be blocked by the ECL1 peptide, a functional ligand to GLP2R, or GLP2R antibodies. GLP2R-deficient mice were generated to validate the role of GLP2R in TBEV infection and pathogenesis. Wild-type mice succumbed to TBEV infection and developed >107 TCID50 (median tissue culture infectious dose) virus per gram of brain tissue. In contrast, all GLP2R-deficient mice survived TBEV infection without detectable infectious virus in brain. Altogether, our results support GLP2R as a receptor for TBEV to infect nerve cells.

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