Tick-borne Encephalitis Vaccination Research Articles

A combined cross-sectional analysis and case-control study evaluating tick-borne encephalitis vaccination coverage, disease and vaccine effectiveness in children and adolescents, Switzerland, 2005 to 2022.

BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17 years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10 years since last vaccination.ConclusionsEven children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.

Identification of New Microfoci and Genetic Characterization of Tick-Borne Encephalitis Virus Isolates from Eastern Germany and Western Poland.

(1) Background: Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia, although effective vaccines are available. Caused by the tick-borne encephalitis virus (TBEV, syn. Orthoflavivirus encephalitidis), in Europe, it is transmitted by ticks like Ixodes ricinus and Dermacentor reticulatus. TBEV circulates in natural foci, making it endemic to specific regions, such as southern Germany and northeastern Poland. Our study aimed to identify new TBEV natural foci and genetically characterize strains in ticks in previously nonendemic areas in Eastern Germany and Western Poland. (2) Methods: Ticks were collected from vegetation in areas reported by TBE patients. After identification, ticks were tested for TBEV in pools of a maximum of 10 specimens using real-time RT-PCR. From the positive TBEV samples, E genes were sequenced. (3) Results: Among 8400 ticks from 19 sites, I. ricinus (n = 4784; 56.9%) was predominant, followed by D. reticulatus (n = 3506; 41.7%), Haemaphysalis concinna (n = 108; 1.3%), and I. frontalis (n = 2; <0.1%). TBEV was detected in 19 pools originating in six sites. The phylogenetic analyses revealed that TBEV strains from Germany and Poland clustered with other German strains, as well as those from Finland and Estonia. (4) Conclusions: Although there are still only a few cases are reported from these areas, people spending much time outdoors should consider TBE vaccination.

Structural diversity of tick-borne encephalitis virus particles in the inactivated vaccine based on strain Sofjin

ABSTRACT The main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype. A 3.8 Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows a high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for the design of novel vaccines against diseases caused by flaviviruses.

Defining the "Correlate(s) of Protection" to tick-borne encephalitis vaccination and infection - key points and outstanding questions.

Tick-borne Encephalitis (TBE) is a severe disease of the Central Nervous System (CNS) caused by the tick-borne encephalitis virus (TBEV). The generation of protective immunity after TBEV infection or TBE vaccination relies on the integrated responses of many distinct cell types at distinct physical locations. While long-lasting memory immune responses, in particular, form the basis for the correlates of protection against many diseases, these correlates of protection have not yet been clearly defined for TBE. This review addresses the immune control of TBEV infection and responses to TBE vaccination. Potential correlates of protection and the durability of protection against disease are discussed, along with outstanding questions in the field and possible areas for future research.

Seroprevalence of tick-borne encephalitis virus and vaccination coverage of tick-borne encephalitis, Sweden, 2018 to 2019.

BackgroundIn Sweden, information on seroprevalence of tick-borne encephalitis virus (TBEV) in the population, including vaccination coverage and infection, is scattered. This is largely due to the absence of a national tick-borne encephalitis (TBE) vaccination registry, scarcity of previous serological studies and use of serological methods not distinguishing between antibodies induced by vaccination and infection. Furthermore, the number of notified TBE cases in Sweden has continued to increase in recent years despite increased vaccination.AimThe aim was to estimate the TBEV seroprevalence in Sweden.MethodsIn 2018 and 2019, 2,700 serum samples from blood donors in nine Swedish regions were analysed using a serological method that can distinguish antibodies induced by vaccination from antibodies elicited by infection. The regions were chosen to reflect differences in notified TBE incidence.ResultsThe overall seroprevalence varied from 9.7% (95% confidence interval (CI): 6.6-13.6%) to 64.0% (95% CI: 58.3-69.4%) between regions. The proportion of vaccinated individuals ranged from 8.7% (95% CI: 5.8-12.6) to 57.0% (95% CI: 51.2-62.6) and of infected from 1.0% (95% CI: 0.2-3.0) to 7.0% (95% CI: 4.5-10.7). Thus, more than 160,000 and 1,600,000 individuals could have been infected by TBEV and vaccinated against TBE, respectively. The mean manifestation index was 3.1%.ConclusionA difference was observed between low- and high-incidence TBE regions, on the overall TBEV seroprevalence and when separated into vaccinated and infected individuals. The estimated incidence and manifestation index argue that a large proportion of TBEV infections are not diagnosed.

Inapparent Tick-Borne Orthoflavivirus Infection in Macaca fascicularis: A Model for Antiviral Drug and Vaccine Research.

Tick-borne encephalitis virus (TBEV) and Powassan virus (POWV) are neurotropic tick-borne orthoflaviviruses. They cause mostly asymptomatic infections in hosts, but severe forms with CNS involvement can occur. Studying the early stages of viral infections in humans is challenging, and appropriate animal models are essential for understanding the factors determining the disease severity and for developing emergency prophylaxis and treatment options. In this work, we assessed the model of the early stages of TBEV and POWV mono- and co-infections in Macaca fascicularis. Serological, biochemical, and virological parameters were investigated to describe the infection, including its impact on animal behavior. Viremia, neutralizing antibody dynamics, and viral load in organs were chosen as the main parameters distinguishing early-stage orthoflavivirus infection. Levels of IFNα, monocyte count, and cognitive test scores were proposed as additional informative indicators. An assessment of a tick-borne encephalitis vaccine using this model showed that it provided partial protection against POWV infection in Macaca fascicularis without signs of antibody-dependent enhancement of infection.

Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.

Ixodes species ticks but can also be acquired less frequently by alimentary transmission. Other rare modes of transmission include through breastfeeding, blood transfusion, solid organ transplantation, and slaughtering of viremic animals. TBE virus can cause acute neurologic disease, which usually results in hospitalization, often permanent neurologic or cognitive sequelae, and sometimes death. TBE virus infection is a risk for certain travelers and for laboratory workers who work with the virus. In August 2021, the Food and Drug Administration approved Ticovac TBE vaccine for use among persons aged ≥1 year. This report summarizes the epidemiology of and risks for infection with TBE virus, provides information on the immunogenicity and safety of TBE vaccine, and summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of TBE vaccine among U.S. travelers and laboratory workers.

Tick-Borne Encephalitis Virus Vaccination among Tourists in a High-Prevalence Area (Italy, 2023): A Cross-Sectional Study.

Tick-borne encephalitis (TBE) represents a potential health threat for tourists in high-risk areas, including the Dolomite Mountains in northeastern Italy. The present questionnaire-based survey was, therefore, designed in order to assess knowledge, attitudes, and preventive practices (KAP) in a convenience sample of Italian tourists visiting the Dolomite Mountains, who were recruited through online discussion groups. A total of 942 participants (39.2% males, with 60.2% aged under 50) filled in the anonymous survey from 28 March 2023 to 20 June 2023. Overall, 24.1% of participants were vaccinated against TBE; 13.8% claimed to have previously had tick bites, but no cases of TBE were reported. The general understanding of TBE was relatively low; while 79.9% of participants acknowledged TBE as a potentially severe disease, its occurrence was acknowledged as high/rather high or very high in the Dolomites area by only 51.6% of respondents. Factors associated with the TBE vaccine were assessed by the calculation of adjusted odds ratios (aOR) and 95% confidence intervals through a logistic regression analysis model. Living in areas considered at high risk for TBE (aOR 3.010, 95%CI 2.062-4.394), better knowledge on tick-borne disorders (aOR 1.515, 95%CI 1.071-2.142), high risk perception regarding tick-borne infections (aOR 2.566, 95%CI 1.806-3.646), a favorable attitude toward vaccinations (aOR 3.824, 95%CI 1.774-8.224), and a tick bite(s) in a previous season (aOR 5.479, 95%CI 3.582-8.382) were characterized as being positively associated with TBE vaccination uptake. Conversely, being <50 years old (aOR 0.646, 95%CI, 0.458-0.913) and with a higher risk perception regarding the TBE vaccine (aOR 0.541, 95%CI 0.379-0.772) were identified as the main barriers to vaccination. In summary, tourists to the high-risk area of the Dolomites largely underestimate the potential occurrence of TBE. Even though the uptake of the TBE vaccine in this research was in line with European data, public health communication on TBE is required in order to improve acceptance of this effective preventive option.

Effect of previous heterologous flavivirus vaccinations on human antibody responses in tick-borne encephalitis and dengue virus infections.

Arthropod-borne flaviviruses include a number of medically relevant human pathogens such as the mosquito-borne dengue (DEN), Zika, and yellow fever (YF) viruses as well as tick-borne encephalitis virus (TBEV). All flaviviruses are antigenically related and anamnestic responses due to prior immunity can modulate antibody specificities in subsequent infections or vaccinations. In our study, we analyzed the induction of broadly flavivirus cross-reactive antibodies in tick-borne encephalitis (TBE) and DEN patients without or with prior flavivirus exposure through TBE and/or YF vaccination, and determined the contribution of these antibodies to TBE and dengue virus (DENV) neutralization. In addition, we investigated the formation of cross-reactive antibodies in TBE-vaccination breakthroughs (VBTs). A TBEV infection without prior YF or TBE vaccination induced predominantly type-specific antibodies. In contrast, high levels of broadly cross-reactive antibodies were found in samples from TBE patients prevaccinated against YF as well as in DEN patients prevaccinated against TBE and/or YF. While these cross-reactive antibodies did not neutralize TBEV, they were effective in neutralizing DENV. This discrepancy points to structural differences between the two viruses and indicates that broadly cross-reactive epitopes are less accessible in TBEV than in DENV. In TBE VBT infections, type-specific antibodies dominated the antibody response, thus revealing no difference from that of unvaccinated TBE patients. Our results emphasize significant differences in the structural properties of different flaviviruses that have an impact on the induction of broadly cross-reactive antibodies and their functional activities in virus neutralization.

The long-term efficacy of tick-borne encephalitis vaccines available in Europe - a systematic review

BackgroundDespite the availability of vaccination, TBE (tick-borne encephalitis) remains a global public health problem. Therefore, the aim of our study was to assess the long-term efficacy of vaccinations against tick-borne encephalitis using vaccines available on the European market.MethodsThe analysis was conducted on the results of a systematic review conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed in three databases, namely Medline (via PubMed), EMBASE (via Ovid), and the Cochrane Library database. The authors followed the PRISMA method and the selection of the articles was performed with two independent researchers.ResultsFrom a total of 199 citations, 9 studies were included in this review. According to the primary studies identified in the search, the efficacy of available anti-TBE vaccines ranges from 90.1% to 98.9%; however, in individuals above the age of 60, the protection wanes as early as one year after vaccination. Administration of a booster dose 3 years after completion of the basic vaccination schedule significantly extended the period of protection against TBE.ConclusionsAnti-TBE vaccines available in Europe have a high level of efficacy. However, the level of protection against TBE is decreasing after vaccination. Therefore, in addition to the conventional schedule, booster vaccines should be administered every 5 years in individuals before the age of 60 and more frequently, e.g. every 3 years, in individuals aged 60 and beyond.

Study of a tick-borne encephalitis vaccine

Scientific relevance. Tick-borne encephalitis is one of the most significant anthropozoonoses for public health in the Russian Federation. Wide vaccination coverage is required to control this zoonotic infection. However, large-scale immunisation is not feasible without developing novel vaccines with improved safety and efficacy profiles, such as vaccines based on the continuous Vero cell line.Aim. This extended study aimed to investigate the key quality attributes of VeroKSEN, a new tick-borne encephalitis vaccine that was obtained using Vero cells.Materials and methods. The authors implemented current approaches to vaccine development, including propagation of tick-borne encephalitis strain 205 (Far Eastern subtype) in Vero cells, fine purification of the viral antigen by size-exclusion chromatography on polymeric resins, and introduction of additional quality control methods. For VeroKSEN production, the authors used the method protected by utility patent No. 2678431. Quality control of the finished product was performed according to the State Pharmacopoeia of the Russian Federation. The laboratory study of the vaccine and its intermediates in Balb/с mice used novel control methods developed by the authors. Additional methods included polyacrylamide gel electrophoresis, enzyme immunoassay, immunoblotting with total antibodies to tick-borne encephalitis virus and monoclonal antibodies to glycoprotein E, reverse transcription–polymerase chain reaction, and high-performance liquid chromatography. The extended potency study used test strains of different subtypes, including Absettarov (Western), Sofjin (Far Eastern), and Korzukhin (Siberian). The authors studied the infectious activity of tick-borne encephalitis virus in outbred mice using the pharmacopoeial titration method. Statistical analysis of the study results involved calculating the arithmetic mean and the root-mean-square deviation.Results. The authors studied the key quality attributes of VeroKSEN and its intermediates. Selected inactivation conditions reduced the infectious activity of the viral harvest to an undetectable level within 24 h, while its antigenic activity remained approximately 100% of the baseline. The fine purification stages and the methods and techniques developed by the authors provided a whole-virion fraction with a purity of up to 98.2% and removed process-related impurities (residual host-cell DNA, bovine serum albumin, formaldehyde, and bacterial endotoxins) to the levels required by national legislation. The stability study demonstrated that the vaccine met the requirements for up to 36 months.Conclusions. The study showed the high potency of the new vaccine in terms of protection against the Western, Siberian, and Far Eastern subtypes of tick-borne encephalitis, with minimum immunising doses (MID50) of 0.007, 0.00125, and 0.00093 mL, respectively.

Arbovirology and Cold War Collaborations: A Transnational History of the Tick-borne Encephalitis Vaccine, 1930-1980.

This article analyzes the history of immunization against tick-borne encephalitis (TBE) and specifically the processes that led to the creation and application of TBE vaccines in the Soviet Union and Austria. Rather than presenting the development of TBE vaccines from the perspective of national scientific schools, the article investigates their history as a transnational project, focusing on the connections among the Soviet Union, Czechoslovakia, Austria, the United States, and the United Kingdom. It argues that biomedical research on TBE was profoundly intertwined with political and military agendas and depended on civil international cooperation as well as Soviet, American, and British military concerns, infrastructures and funding. The article consists of four parts that discuss (1) the identification of the TBE virus and the creation of the first TBE vaccine in the Soviet Union in the 1930s; (2) the internationalization of TBE research and vaccine development in the 1940s-1960s; (3) the history of TBE research and virology in Austria in the 1930s-1960s and the role of the US military funding; and (4) the cooperation of Austrian virologist Christian Kunz with the Microbiological Research Establishment Porton Down in the UK leading to the development of the Austrian/British vaccine against TBE in the 1970s.

Arboviral vaccines for use in pregnant travelers

Pregnant women traveling abroad can be exposed to a variety of arboviruses, primarily spread by mosquitoes or ticks. Some arboviral infections can be of particular concern for pregnant women or their fetuses. Vaccination is one preventive measure that can reduce the risk for infection. Several arboviral vaccines have been licensed for many years and can be used to prevent infection in travelers, namely Japanese encephalitis, yellow fever, and tick-borne encephalitis vaccines. Recommendations on use of these vaccines in pregnancy vary. Other arboviral vaccines have been licensed but are not indicated for use in pregnant travelers (e.g., dengue vaccines) or are in development (e.g., chikungunya, Zika vaccines). This review describes arboviral vaccines for travelers, focusing on women who are pregnant and those planning travel during pregnancy.

Effectiveness of tick-borne encephalitis vaccination in Latvia, 2018–2020: an observational study

ObjectivesTick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) that results in symptoms of central nervous system inflammation. TBE is endemic in Latvia and other European countries. TBE vaccines are commonly used in Latvia, but vaccine effectiveness estimates are limited. MethodsStudy staff at Rīga Stradinš University conducted nationwide active surveillance for TBEV infections. Serum and cerebrospinal fluid were ELISA-tested for TBEV-specific IgG and IgM antibodies. Vaccination history was collected by interview and medical record review. Utilizing data from surveillance and population surveys, vaccine effectiveness (with 95% CIs) and cases averted were estimated using the screening method. ResultsThere were 587 laboratory-identified TBE cases from 2018 to 2020; 98.1% (576/587) were unvaccinated, 1.5% (9/587) were unknown or partially vaccinated, and 0.3% (2/587) were fully vaccinated (three-dose primary series and appropriately timed boosters). TBE resulted in the death of 1.7% (10/587) of TBE cases. TBE vaccine history was ascertained from 92.0% (13 247/14 399) people from the general population: 38.6% (5113/13 247) were unvaccinated, 26.3% (3484/13 247) were fully vaccinated, and 35.1% (4650/13 247) were partially vaccinated. TBE vaccine effectiveness was 99.5% (98.0–99.9) against TBE, 99.5% (97.9–99.9) against TBE hospitalization, 99.3% (94.8–99.9) against moderate/severe TBE, and 99.2% (94.4–99.9) against TBE hospitalization >12 days. From 2018 to 2020, vaccination averted 906 TBE cases, including 20 deaths. DiscussionTBE vaccine was highly effective in preventing TBE, moderate and severe disease, and prolonged hospitalization. To prevent life-threatening TBE, TBE vaccine uptake and compliance should be increased in Latvia and other European regions where TBE is endemic.

Development of ahighly purified tick-borne encephalitis vaccine : Apersonal historical account.

Before the advent of avaccine, infections with tick-borne encephalitis (TBE) virus in Austria led to the hospitalization of several hundred and, due to underreporting, possibly more than thousand patients with severe neurological disease every year. In the late 1960s and early 1970s, this country had the highest recorded morbidity of TBE in Europe, but similar endemic risk areas exist in many other European countries as well as Central and Eastern Asia. In this article, Idescribe my personal recollections of the development of ahighly purified TBE vaccine in the late 1970s, to which Icontributed as ayoung post-doctoral scientist mentored by Christian Kunz (then director of the Institute of Virology at the Medical Faculty, University of Vienna) in acollaboration with the Austrian biopharmaceutical company Immuno. Low reactogenicity of the newly developed vaccine was aprerequisite for mass vaccination campaigns in Austria that started in the early 1980s. Because of its excellent immunogenicity, broad application of the highly purified vaccine paved the way for adramatic reduction of the incidence of TBE in Austria, which is outstanding in Europe and referred to as an Austrian success story of immunoprophylaxis.

Effectiveness of Tick-borne Encephalitis Vaccines in Children, Latvia, 2018-2020.

Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1-15 years-of-age. Rīga Stradinš University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1-15 years-of-age was estimated using the screening method: VE = 1 - [PCV/(1 - PCV)/PPV/(1 - PPV)]. From 2018 to 2020, surveillance identified 36 TBE cases in children 1-15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1-15 years-of-age was 94.9% (95% confidence interval 63.1-99.3). In 2018-2020, vaccination in children 1-15 years-of-age averted 39 hospitalized TBE cases. Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (&gt;3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

Chapter 6: TBE in children

Most cases of TBE in childhood will present similarly as in adults. However, a more diffuse clinical picture is seen especially in preschool children. Laboratory evaluation may show elevated blood inflammatory indices, but cerebrospinal fluid analysis and anti-TBEV serology are needed for establishing the diagnosis. There is no specific treatment for TBE; supportive care needs to be provided based on the individual clinical course. The mortality in pediatric TBE is very low but severe courses have been reported in a fraction of the children. Long-term somatic residua exist, but are uncommon (2%) in childhood TBE. Yet, long-term symptoms and neurodevelopmental/cognitive deficits are seen in 10–40% of infected children. Protective immunity can be elicited in children by TBE vaccines as of 1 year of age.

Sustained antibody persistence for at least 15years after a booster vaccination against tick-borne encephalitis following different primary vaccination schedules: Third 5-year follow-up.

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 11-15years after a first booster vaccination following different primary vaccination schedules with a TBE vaccine (Encepur Adults, manufactured by Bavarian Nordic, previously by GSK). This phase IV, open-label, mono-centric extension study enrolled adults who had received (at≥12years 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 3years later. The antibody response was measured annually from 11 to 15years 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. 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≥50years old (98-206) and≥60years old (91-191) across study groups and time points. This study showed neutralizing antibody persistence for at least 15years 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.

The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland.

The AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.