Tick-borne encephalitis virus (TBEV) is a major cause of neurological infections in many regions of central, eastern and northern Europe and northern Asia. In approximately 15% of cases, TBEV infections lead to the development of severe encephalitis or meningitis. The main route of TBEV transmission is tick bites; however, ingestion of dairy products from infected animals (goats, cattle and sheep) is also a frequent cause of the disease. Therefore, vaccination of livestock in virus endemic regions could also contribute to the decrease in TBEV infection among humans. Although few vaccines against TBEV based on inactivated viruses are available for humans, due to high costs, vaccination is not mandatory in most of the affected countries. Moreover, there is still no vaccine for veterinary use. Here, we present a characterization and immunogenicity study of a new potential TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells. VLPs, which mimic native viral particles but do not contain genetic material, show good immunogenic potential. For the first time, we showed that the protozoan L. tarentolae expression system can be successfully used for the production of TBEV virus-like particles with highly efficient production. We confirmed that TBEV recombinant structural proteins (prM/M and E) from VLPs are highly recognized by neutralizing antibodies in in vitro analyses. Therefore, VLPs in combination with AddaVax adjuvant were used in immunization studies in a mouse model. VLPs proved to be highly immunogenic and induced the production of high levels of neutralizing antibodies. In a challenge experiment, immunization with VLPs provided full protection from lethal TBE in mice. Thus, we suggest that Leishmania-derived VLPs may be a good candidate for a safe alternative human vaccine with high efficiency of production. Moreover, this potential vaccine candidate may constitute a low-cost candidate for veterinary use.
- MeSH
- klíšťová encefalitida * prevence a kontrola MeSH
- Leishmania * MeSH
- lidé MeSH
- myši MeSH
- neutralizující protilátky MeSH
- ovce MeSH
- protilátky virové MeSH
- skot MeSH
- virové vakcíny * MeSH
- viry klíšťové encefalitidy * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Vaccine-induced protection against tick-borne encephalitis virus (TBEV) is mediated by antibodies to the viral particle/envelope protein. The detection of non-structural protein 1 (NS1) specific antibodies has been suggested as a marker indicative of natural infections. However, recent work has shown that TBEV vaccines contain traces of NS1, and immunization of mice induced low amounts of NS1-specific antibodies. In this study, we investigated if vaccination induces TBEV NS1-specific antibodies in humans. Healthy army members (n = 898) were asked to fill in a questionnaire relating to flavivirus vaccination or infection, and blood samples were collected. In addition, samples of 71 suspected acute TBE cases were included. All samples were screened for the presence of TBEV NS1-specific IgG antibodies using an in-house developed ELISA. Antibodies were quantified as percent positivity in reference to a positive control. For qualitative evaluation, cut-off for positivity was defined based on the mean OD of the lower 95% of the vaccinated individuals + 3 SD. We found significantly higher NS1-specific IgG antibody titers (i.e., quantitative evaluation) in individuals having received 2, 3, or 4 or more vaccine doses than in non-vaccinated individuals. Similarly, the percentage of individuals with a positive test result (i.e., qualitative evaluation) was higher in individuals vaccinated against tick-borne encephalitis than in unvaccinated study participants. Although NS1-specific IgG titers remained at a relatively low level when compared to TBE patients, a clear distinction was not always possible. Establishing a clear cut-off point in detection systems is critical for NS1-specific antibodies to serve as a marker for distinguishing the immune response after vaccination and infection.
Tick-borne encephalitis (TBE) is a severe neuroinfection of humans. Dogs are also commonly infected with tick-borne encephalitis virus (TBEV). These infections are usually asymptomatic, but sometimes show clinical signs similar to those seen in humans and can be fatal. To date, there is no TBEV vaccine available for use in dogs. To address this need, a TBEV vaccine candidate for dogs based on inactivated whole virus antigen was developed. The safety, immunogenicity, and efficacy of the vaccine candidate were tested in mice as the preclinical model and in dogs as the target organism. The vaccine was well tolerated in both species and elicited the production of specific anti-TBEV antibodies with virus neutralising activity. Vaccination of mice provided complete protection against the development of fatal TBE. Immunisation of dogs prevented the development of viremia after challenge infection. Therefore, the developed vaccine candidate is promising to protect dogs from severe TBEV infections.
- MeSH
- imunizace MeSH
- klíšťová encefalitida * prevence a kontrola veterinární MeSH
- lidé MeSH
- myši MeSH
- protilátky virové MeSH
- psi MeSH
- vakcinace MeSH
- virové vakcíny * MeSH
- viry klíšťové encefalitidy * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tick-borne encephalitis virus (TBEV) is a flavivirus commonly found in at least 27 European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick-borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive-sense single-stranded RNA molecule of ∼11 kilobases. The open reading frame is > 10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co- and post-transcriptionally processed into three structural and seven non-structural proteins. Tick-borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non-specific influenza-like symptoms. After an asymptomatic period of 2-7 days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low-around 1% of confirmed cases, depending on the viral subtype. After acute tick-borne encephalitis (TBE), a minority of patients experience long-term neurological deficits. Additionally, 40%-50% of patients develop a post-encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long-lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.
BACKGROUND: Vaccination is the best mode of protection against tick-borne encephalitis (TBE) and its sequelae. The duration of protection and the optimal interval of repeat booster doses are still debated. The current study evaluated the persistence of the antibody response 11-15 years after a first booster vaccination following different primary vaccination schedules with a TBE vaccine (Encepur Adults, manufactured by Bavarian Nordic, previously by GSK). METHODS: This phase IV, open-label, mono-centric extension study enrolled adults who had received (at ≥ 12 years of age) primary vaccination with one of three randomly assigned TBE vaccine schedules (rapid [group R], conventional [group C], or accelerated conventional schedule [group A]) followed by a booster dose 3 years later. The antibody response was measured annually from 11 to 15 years post-booster using a TBE virus neutralization test (NT). An NT titer of ≥ 10 was considered as a clinically meaningful threshold and surrogate for protection. RESULTS: In total, 194 participants were enrolled and included in the per-protocol set; 188 completed the study. The percentage of participants with an NT titer ≥ 10 was 100% in group R and 99.0% in group A at all visits and ranged from 100% (year 11) to 95.8% (year 15) in group C. NT geometric mean titers were similar in the three study groups (181-267 in group R, 142-227 in group C, 141-209 in group A). NT geometric mean titers also remained high among participants ≥ 50 years old (98-206) and ≥ 60 years old (91-191) across study groups and time points. CONCLUSIONS: This study showed neutralizing antibody persistence for at least 15 years after a first booster dose of the Encepur Adults TBE vaccine in all age groups evaluated, regardless of which primary vaccination schedule was given to adolescents or adults. Trialregistry: ClinicalTrials.gov: NCT03294135.
- MeSH
- dospělí MeSH
- klíšťová encefalitida * prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- očkovací schéma MeSH
- předškolní dítě MeSH
- protilátky virové MeSH
- sekundární imunizace MeSH
- vakcinace MeSH
- virové vakcíny * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BackgroundTick-borne encephalitis (TBE) is a vaccine-preventable disease involving the central nervous system. TBE became a notifiable disease on the EU/EEA level in 2012.AimWe aimed to provide an updated epidemiological assessment of TBE in the EU/EEA, focusing on spatiotemporal changes.MethodsWe performed a descriptive analysis of case characteristics, time and location using data of human TBE cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease onset in 2012-2020. We analysed data at EU/EEA, national, and subnational levels and calculated notification rates using Eurostat population data. Regression models were used for temporal analysis.ResultsFrom 2012 to 2020, 19 countries reported 29,974 TBE cases, of which 24,629 (98.6%) were autochthonous. Czechia, Germany and Lithuania reported 52.9% of all cases. The highest notification rates were recorded in Lithuania, Latvia, and Estonia (16.2, 9.5 and 7.5 cases/100,000 population, respectively). Fifty regions from 10 countries, had a notification rate ≥ 5/100,000. There was an increasing trend in number of cases during the study period with an estimated 0.053 additional TBE cases every week. In 2020, 11.5% more TBE cases were reported than predicted based on data from 2016 to 2019. A geographical spread of cases was observed, particularly in regions situated north-west of known endemic regions.ConclusionA close monitoring of ongoing changes to the TBE epidemiological situation in Europe can support the timely adaption of vaccination recommendations. Further analyses to identify populations and geographical areas where vaccination programmes can be of benefit are needed.
- MeSH
- klíšťová encefalitida * epidemiologie prevence a kontrola MeSH
- lidé MeSH
- vakcinace MeSH
- virové vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Německo MeSH
- MeSH
- antivirové látky * MeSH
- klíšťová encefalitida prevence a kontrola MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- SARS-CoV-2 MeSH
- virové vakcíny MeSH
- vyvíjení léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- rozhovory MeSH
x
x
- MeSH
- hlášení nemocí MeSH
- incidence MeSH
- klíšťová encefalitida * epidemiologie přenos prevence a kontrola MeSH
- lidé MeSH
- surveillance populace MeSH
- vakcinace MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- klíšťová encefalitida * epidemiologie prevence a kontrola MeSH
- lidé MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
Česká republika patří k zemím s nejvyšším výskytem klíšťové encefalitidy v Evropě. K nákaze dochází prakticky ve všech okresech České republiky ve venkovských i městských částech včetně Prahy. Onemocnění postihuje děti i dospělé, dlouhodobě nejvyšší incidence je pozorována ve věkové skupině mezi 50 a 75 lety. Trend výskytu klíšťové encefalitidy je rostoucí také u osob nad 35 let a výrazně vzestupný je trend výskytu nemoci i u dětí školního a předškolního věku. Časté následky klíšťové encefalitidy ovlivňují kvalitu života. Vzhledem k závažnosti této neuroinfekce se stále nedostatečně využívá možnosti preventivní vakcinace a proočkovanost v ČR nadále zůstává nízká ve srovnání s jinými endemickými zeměmi. Úhrada očkování proti klíšťové encefalitidě u pojištěnců nad 50 let věku od 1. 1. 2022 by mohla přispět ke zlepšení nepříznivé epidemiologické situace ve výskytu této nemoci.
The Czech Republic belongs to the countries with the highest incidence of tick-borne encephalitis in Europe. The infection occurs in practically all districts of the Czech Republic in rural and urban areas, including Prague. The disease affects both children and adults with the highest incidence observed in the age group between 50 and 75 years. The trend in tick-borne encephalitis incidence is increasing in age groups over 35 years and the trend in the disease incidence is also significantly rising in school-age and pre-school children. Frequently occurring sequelae of tick-borne encephalitis can affect quality of life. Given the severity of this neuroinfection, the preventive vaccination is still utilised insufficiently in the Czech Republic. Vaccination coverage in the Czech Republic remains low compared to other endemic countries. Reimbursement of vaccination against tick-borne encephalitis from health insurance for persons over 50 years of age from 1 January 2022 could contribute to improving the unfavourable epidemiological situation in this disease.
- MeSH
- klíšťová encefalitida * diagnóza epidemiologie prevence a kontrola MeSH
- lidé MeSH
- vakcinace MeSH
- vakcíny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
