Tick-borne Encephalitis Antibodies Research Articles

TBE in Denmark

Since the 1950s, tick-borne encephalitis (TBE) has been known to be endemic in Denmark but only on the island of Bornholm. Bornholm is situated east of mainland Denmark, south of Sweden (Figure 3) and has a different fauna and flora from the rest of Denmark. Bornholm has about 45,000 inhabitants, but about 500,000 tourists visit the island every year. Freundt carried out a serosurvey during 1958–1962 and found TBE antibodies in 1.4% of blood donors and 30% of woodworkers on Bornholm but no antibodies in subjects living in mainland Denmark. In 1963, Freundt found that 8 of 12 patients admitted to the hospital with acute meningoencephalitis of unknown etiology during 1951–1960 had antibodies to tick-borne encephalitis (TBEV). In 2000, TBE was rediscovered on Bornholm, where a retrospective study covering the period 1994–2002 (7 years) identified 14 TBE cases; 2 cases were tourists and 12 were inhabitants of Bornholm, giving an incidence of 3.81 per 100,000 inhabitants. At least 5 patients (37.7%) got permanent sequelae. In addition, 32 forest workers on Bornholm were tested in 2000, and 20% had IgG antibodies but never symptoms. This is similar to the finding of Freundt in 1960. It was concluded that the data did not provide evidence of an increase in incidence of TBE. Ticks (Ixodes ricinus) from Bornholm were investigated for TBEV in 2000 and 2% were found to be infected. Since 2001 an average of 2.5 (range 1–8) TBE cases per year have been reported in Bornholm (Figure 1).

Anti-TBE Intrathecal Synthesis as a Prediction Marker in TBE Patients.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe caused by tick-borne encephalitis virus (TBEV), which belongs to Flaviviridae. Although most of the patients quickly recover from TBE, some require further neurological and psychiatric treatment due to persistent symptoms. The aim of the study was to evaluate the usefulness of an antibodies index for predicting the course of the disease and potential persistent sequalae. Sixty-six patients (49 males and 17 females, mean age 45.97 ± 13.69 years) with TBE hospitalized in the Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Poland, in years 2016–2019 were included to the study. TBE antibodies titer in serum and CSF samples were measured with an Anti-TBEV ELISA (IgM, IgG) EUROIMMUN test. Patients who developed persistent sequelae after TBE had significantly lower IgG intrathecal index at admission. Additionally, IgG2/IgG1was significantly higher in patients who developed sequelae. IgG intrathecal index might be a useful tool for the prediction of TBE sequelae development.

Severe tick-borne encephalitis in a patient recovered from COVID 19

North-eastern Poland is an endemic region for tick-borne encephalitis (TBE). The COVID-19 pandemic overlapped with the activity period of ticks that are the main vectors for TBE. As we know from short observation worldwide, SARS-CoV-2 virus affects significantly the immune system and can lead to serious complications of other infections even in previously healthy patients.A 24-year-old female patient, who lived close to the forest, was admitted to the Department of Neurology at Medical University of Bialystok with fever, dizziness, and progressive left-sided hemiparesis for three days. She had no medical history of chronic disease and was not vaccinated against TBE. The patient had SARS-CoV-2 infection three weeks prior to admission to the hospital (positive IgG against SARS-CoV-2). During COVID-19 infection she had fever, myalgia, a mild dyspnoea without indications for oxygen therapy and recovered after one week. During hospitalisation in the Department of Neurology the patient presented neck stiffness, progressing tetraparesis, dysarthria and weakness of the neck muscles. The magnetic resonance of the head revealed numerous lesions, mainly in both thalamus, longitudinal lesion was found in the cervical spinal cord. The cerebrospinal fluid analysis indicated lymphocytic inflammation. A high level of TBE antibodies in both serum and CSF was found. After immunoglobulin and symptomatic treatment her condition gradually improved. The recovery after SARS-CoV-2 infection overlapping with TBE might have influenced the course of tick-borne disease in a bad manner. The correct diagnosis can be a challenge as COVID-19 can lead to further complications, also neurological. The co-incidence we observed is very rare, however during the pandemic it is pivotal to remember about possible occurrence of other infections and their atypical course.

TBE in Denmark

Since the 1950s tick-borne encephalitis (TBE) has been known to be endemic in Denmark but only on the island of Bornholm. Bornholm is situated east of mainland Denmark, south of Sweden (Figure 3) and has a different fauna and flora from the rest of Denmark. Bornholm has about 45,000 inhabitants, but about 500,000 tourists visit the island every year. Freundt carried out a serosurvey during 1958–19621 and found TBE antibodies in 1.4% of blood donors and 30% of woodworkers on Bornholm but no antibodies in subjects living in mainland Denmark. In 1963, Freundt found that 8 of 12 patients admitted to the hospital with acute meningoencephalitis of unknown etiology during 1951–1960 had antibodies to tick-borne encephalitis (TBEV).2 In 2000, TBE was rediscovered on Bornholm, where a retrospective study covering the period 1994–2002 (7 years) identified 14 TBE cases; 2 cases were tourists and 12 were inhabitants of Bornholm, giving an incidence of 3.81 per 100,000 inhabitants.3 At least 5 patients (37.7%) got permanent sequelae. In addition, 32 forest workers on Bornholm were tested in 2000, and 20% had IgG antibodies but never symptoms. This is similar to the finding of Freundt in 1960. It was concluded that the data did not provide evidence of an increase in incidence of TBE. Ticks (Ixodes ricinus) from Bornholm were investigated for TBEV in 2000 and 2% were found to be infected.4 Since 2001 an average of 2.5 (range 1–8) TBE cases per year have been reported in Bornholm (Figure 1).

Epidemiology, diagnosis, and prevention of tick-borne encephalitis in Poland and selected European countries - a position statement of the Polish group of experts

Tick-borne encephalitis (TBE) is one of the most common viral neuroinfections in Poland. Detection of specific IgM and IgG anti- TBE antibodies in the serum or cerebrospinal fluid with enzyme-linked immunosorbent assay (ELISA) is a method of choice in TBE diagnostics. No effective antiviral treatment is available for TBE. Increased intracranial pressure, epileptic seizures, and other neurological symptoms in the course of TBE are managed with standard procedures. A routine use of corticosteroids is not recommended. Adults with TBE-related neurological sequelae should undergo physical mobilization and periodic neurological assessments. All patients ought to control their psychological condition and visit a physician in case of worrisome symptoms. Additionally, children need to undergo regular psychological and otolaryngologic consultations. Notably, TBE cases are reported across Poland; therefore, the entire country must be considered as a TBE risk region. The degree of endemicity can be variable in particular parts of the country. Immunization against TBE containing a European subtype of the virus is the most effective prophylactic method. In areas where the disease is highly endemic (according to the WHO definition of ≥5 cases/100 000 population/year), immunization needs to be offered to all ages. Vaccination is recommended in the communities living in areas of moderate TBE endemicity (1-5 cases/100 000/ year), in particular for individuals at high risk of a TBE infection as well as children and the elderly. Vaccination should also be offered to subjects living in areas where TBE occurrence is rare (<1 case/100 000/year) but who are at high risk of infection. A TBE vaccine is recommended to the following populations at high risk of TBE: a) individuals undertaking outdoor leisure activities, b) all professionals working outdoors, particularly in green areas, and c) individuals traveling to endemic areas, if activities during their visit may pose a risk of a tick bite. Post-exposure immunization is not recommended. Med Pr. 2021;72(2):193-210.

Tick-Borne Encephalitis Electrochemical Detection by Multilayer Perceptron on Liquid-Metal Interface.

This work depicts an electrochemical hydrogel-eutectic gallium indium alloy interface for the detection of tick-borne encephalitis (TBE) virus. This interface allows recording of nonlinear current-voltage responses, depending on the composition of the hydrogel. The current-voltage data for the machine learning model are trained by a multilayer perceptron. This model accurately recognizes the TBE antibody, antigen, and an antibody-antigen complex in mixture with interfering bovine serum albumin with 93% accuracy. Thus, this interface can be used as a convenient method for expressed viruses and pathogens detection.

Tick-Borne Encephalitis: A Differential Pattern of Intrathecal Humoral Immune Response and Inflammatory Cell Composition Compared with Other Viral CNS Infections.

To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present.

Tick-borne encephalitis vaccination in multiple sclerosis: A prospective, multicenter study.

ObjectiveTo assess the changes in disease activity after tick-borne encephalitis (TBE) vaccination in patients with multiple sclerosis (MS) on a variety of disease-modifying drugs and to assess the immunogenicity, safety, and clinical tolerability of the vaccine in this patient group.MethodsWe conducted a prospective, multicenter, nonrandomized observational study. We enrolled 20 patients with MS receiving TBE vaccination who had been on disease-modifying treatment (DMT) for at least 6 months. Serum samples were obtained before and after 4 weeks of vaccination to determine the specific TBE antibody response. MS disease activity (Expanded Disability Status Scale and relapse rates) was evaluated for 1 year after immunization. Local and systemic adverse events were registered.ResultsIn 20 subjects with TBE vaccination, the annualized relapse rate decreased from 0.65 in the year before vaccination to 0.21 in the following year. Expanded Disability Status Scale remained stable during the 2-year period before vaccination and 1 year after vaccination (range: 1.50–1.97). The geometric mean titer (GMT) increased from 169 Vienna units per milliliter (VIEU/mL) to 719 VIEU/mL 4 weeks after vaccination (p = 0.001), and 77.8% had protective antibody titers after vaccination. In 9 patients treated with beta interferons, GMT increased from 181 VIEU/mL to 690 VIEU/mL (p = 0.018). Three subjects treated with glatiramer acetate developed a 2- to 9.6-fold increase. Patients treated with fingolimod developed the lowest increase in antibody titer.ConclusionTBE vaccination showed good tolerability and was safe in patients with MS. MS disease activity was not increased, and annualized relapse rates decreased after vaccination. Vaccine response differs according to the underlying DMT.Trial registrationClinicalTrials.gov, clinicaltrials.gov, Identifier: NCT02275741.

Cervids as sentinel-species for tick-borne encephalitis virus in Norway - A serological study.

Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE). TBEV is one of the most important neurological pathogens transmitted by tick bites in Europe. The objectives of this study were to investigate the seroprevalence of TBE antibodies in cervids in Norway and the possible emergence of new foci, and furthermore to evaluate if cervids can function as sentinel animals for the distribution of TBEV in the country. Serum samples from 286 moose, 148 roe deer, 140 red deer and 83 reindeer from all over Norway were collected and screened for TBE immunoglobulin G (IgG) antibodies with a modified commercial enzyme-linked immunosorbent assay (ELISA) and confirmed by TBEV serum neutralisation test (SNT). The overall seroprevalence against the TBEV complex in the cervid specimens from Norway was 4.6%. The highest number of seropositive cervids was found in south-eastern Norway, but seropositive cervids were also detected in southern- and central Norway. Antibodies against TBEV detected by SNT were present in 9.4% of the moose samples, 1.4% in red deer, 0.7% in roe deer, and nil in reindeer. The majority of the positive samples in our study originated from areas where human cases of TBE have been reported in Norway. The study is the first comprehensive screening of cervid species in Norway for antibodies to TBEV, and shows that cervids are useful sentinel animals to indicate TBEV occurrence, as supplement to studies in ticks. Furthermore, the results indicate that TBEV might be spreading northwards in Norway. This information may be of relevance for public health considerations and supports previous findings of TBEV in ticks in Norway.

Effectiveness of primary vaccination against tick-borne encephalitis in employees of the armed forces.

The aim of our study is to evaluate immune response after receiving the primary vaccination against tick-borne encephalitis (TBE), and to establish a link between seropositivity and selected factors in soldiers. Blood samples, questionnaires and vaccination records were obtained. TBE antibodies were detected using both ELISA and a neutralization test (NT). We used logistic regression for statistical analysis. Overall, seropositivity (presence of IgG) was detected in 88% of participants. The proportion of seropositive subjects in relation to the number of doses of vaccine was 69% (2 doses) and 91% (3 doses). A statistically significant relationship was found between seropositivity and the number of vaccine doses. No statistical significance was identified in relation to age and sex. There was no statistical significance of seropositivity, depending on the time of the last dose of the vaccine. TBE immunisation should be targeted at individuals in the most affected locations and those at highest risk of exposure according to lifestyle and occupation.

Seropersistence of TBE virus antibodies 10 years after first booster vaccination and response to a second booster vaccination with FSME-IMMUN 0.5 mL in adults

Tick-borne encephalitis (TBE) is a viral disease that can have a severe acute clinical course and considerable long-term morbidity. As there is no causal treatment currently available for TBE, vaccination is the only way to combat the disease in endemic areas. The studies presented here were conducted to obtain prospective long-term TBE serum antibody persistence data of subjects up to 10years after the first booster with FSME-IMMUN.This report presents the results of 2 follow-up studies in the same study population of 315 healthy adults. Blood was drawn to assess the seropersistence of TBE virus antibodies yearly, from 2–5 and 7–10years after the first booster vaccination with FSME-IMMUN administered during a previous study. The timing of the second booster vaccination was dependent on the level of serum TBE antibodies observed during yearly follow-up serology observations.The current follow up showed that adult recipients were 84.9% seropositive 10years after a 3 dose primary series and the first booster vaccination of FSME-IMMUN. Seropositivity rates were even higher (88.6%) in subjects below 50years of age.ClinicalTrials.gov Identifier: NCT00503529.ClinicalTrials.gov Identifier: NCT01582698.

Five year follow-up after primary vaccination against tick-borne encephalitis in children

BackgroundA first tick-borne encephalitis (TBE) vaccine booster in children is currently suggested 3 years after completing either a conventional (doses on Days 0, 28 and 300) or accelerated conventional (doses on Days 0, 14 and 300) TBE immunization schedule. This recommendation, however, may not be appropriate in cases where different TBE vaccines have been used interchangeably during the primary immunization series. MethodsTo provide robust data to better inform such recommendations, TBE antibody persistence was evaluated after 3–5 years in four groups of children (aged 5–15 years): two groups previously primed with three doses of Encepur® Children (conventional/accelerated conventional schedule); and two groups previously primed with two doses of FSME-IMMUN® followed by a third dose of Encepur® Children (conventional/accelerated conventional schedule). Immunogenicity was evaluated using neutralization (NT) assays based on both vaccine antigens as well as on the Enzyme Linked Immunosorbent Assay (ELISA). ResultsIn the two Encepur® Children groups (full series), protective NT titers of ≥10 were detected in 98–100% of children up to 5 years after their last primary vaccination, irrespective of schedule. In contrast, only 65–70% subjects in the FSME-IMMUN® Junior groups (mixed series) displayed NT titers ≥10 after 3 years. Thus, due to lower probability of achieving/maintaining long-term protective antibody levels (recently defined by the World Health Organization as an NT titer ≥10) after this time point, both FSME-IMMUN Junior groups were discontinued. ConclusionA strong antibody response persists for at least 5 years after full primary vaccination with Encepur® Children. The study thus provides support for extending the time interval for a first booster dose after primary vaccination (conventional/accelerated conventional schedule) with Encepur® Children from 3 to 5 years.

Five year follow-up after a first booster vaccination against tick-borne encephalitis following different primary vaccination schedules demonstrates long-term antibody persistence and safety

Long-term vaccination programs are recommended for individuals living in regions endemic for tick-borne encephalitis (TBE). Current recommendations suggest a first booster vaccine be administered 3 years after a conventional regimen or 12–18 months after a rapid regimen. However, the research supporting subsequent booster intervals is limited. The aim of this study was thus to evaluate the long-term persistence of TBE antibodies in adults and adolescents after a first booster dose with Encepur®. A total of 323 subjects aged 15 years and over, who had received one of four different primary TBE vaccination series in a parent study, participated in this follow-up Phase IV trial. Immunogenicity and safety were assessed for up to five years after a first booster dose, which was administered three years after completion of the primary series. One subset of subjects was excluded from the booster vaccination since they had already received their booster prior to enrolment. For comparison, immune responses were still recorded for these subjects on Day 0 and on an annual basis until Year 5, but safety information was not collected. Following a booster vaccination, high antibody titers were recorded in all groups throughout the study. Neutralization test (NT) titers of ≥10 were noted in at least 94% of subjects at every time point post-booster (on Day 21 and through Years 1–5). These results demonstrated that a first booster vaccination following any primary immunization schedule results in high and long-lasting (>5 years) immune responses. These data lend support to the current belief that subsequent TBE booster intervals could be extended from the current recommendation. NCT00387634.

Persistence of immunity to tick‐borne encephalitis after vaccination and natural infection

Long-term persistence of immunity was assessed in 66 patients who had contracted tick-borne encephalitis (TBE) and in 126 subjects who had completed primary TBE immunization using a conventional three-dose schedule from 3 to 8 years earlier. Immunity was tested in the subjects stratified by age as follows: ≤40 years (N = 37); 41-60 years (N = 100); and over 60 years (N = 55). Antibody levels decreased significantly with increasing age in the vaccinated cohort by comparison with the individuals who had previously contracted TBE. Consistently higher geometric mean antibody levels were found in the patients infected naturally. When the vaccinated subjects were compared, subjects ≤40 years old had significantly higher antibody levels than either of the older groups. Analyzing immunity to TBE over time revealed a remarkable (50%) decline in seroprotection rates in the vaccinated group at 50 months of follow-up, while stable, high levels persisted in all subjects after natural TBE infection. In the vaccinees over 60 years old, the TBE antibody levels reached 60% at 60 months, and 20% at 70 months of follow-up; in contrast, in the 41-60-year-old group, the antibody levels remained high for 70 months, and then fell rapidly. For people aged <60 years old, booster doses are recommended every 5 years after the fourth dose of vaccine, which should be administered 3 years after primary immunization. In subjects aged 60 years or older, booster doses should be given every 3 years.

Seropersistence of tick-borne encephalitis antibodies, safety and booster response to FSME-IMMUN® 0.5 ml in adults aged 18-67 years

A clinical study was carried out to evaluate the persistence of tick-borne encephalitis (TBE) antibodies 2 and 3 years after a primary vaccination series (three-dose regimen), and to assess the antibody response to a booster vaccination with FSME-IMMUN®. Volunteers (N=347, 18–67 years) who had received 2 doses of either FSME-IMMUN® or Encepur® adults and a third vaccination with FSME-IMMUN® were enrolled. Seropositivity rates were assessed by ELISA and neutralization test (NT). After the primary series, seropositivity rates were 99.1% as determined by ELISA and 100% by NT, decreasing to 85% and 96.8% in the first 2 years and to 88.7% and 95.4% after 3 years. Following booster vaccination, 100% of subjects were seropositive. Age was the only variable with a significant influence on the probability of remaining TBE seropositive 2 or 3 years after the third vaccination. In subjects aged 18–50 years, the pre-booster seropositivity rate was higher (88.7% and 92.3% after 2 and 3 years, respectively) than in those aged 51–67 years (65.5% and 70.9% after 2 and 3 years, respectively). Adverse events after booster vaccination occurred with a low frequency and were predominantly mild. An annual TBE antibody decline rate of 0.58 (based on NT) was estimated to lead to antibody titer decrease from e.g. 260 to 45.6 after 3 years. To conclude, a booster vaccination with FSME-IMMUN®, administered 3 years after primary vaccination, is well tolerated and induces a substantial immune response regardless of vaccine used in the primary series.

Long-term persistence of tick-borne encephalitis antibodies in children 5 years after first booster vaccination with Encepur ® Children

Tick-borne encephalitis (TBE) is a serious viral infection, which can lead to permanent neurological sequelae in children. The incidence of TBE disease is increasing in many European countries and is particularly pronounced in some regional populations. Vaccination is the most effective method for preventing TBE disease and is recommended for all those living and working in TBE-endemic areas. Encepur ® Children is licensed for TBE vaccination in children 1–11 years of age. Following primary vaccination, booster vaccinations are recommended; however, the optimal timing for booster vaccination of children is not known. The aim of this study was to assess the persistence of TBE antibodies in children at 3 and 5 years after their first booster vaccination with Encepur ® Children and to re-evaluate booster vaccination recommendations. Children 1–11 years of age ( n = 335) who received primary TBE vaccination according to the rapid schedule (Days 0, 7, and 21) in a previous study received a booster vaccination 12–18 months later, and were invited for follow-up at 3 and 5 years post-booster. TBE antibodies were measured using a virus neutralization test (NT; in-house, Novartis Vaccines) and also using anti-TBE IgG ELISA (Enzygnost ®, Siemens, Germany). In this analysis, 275 of 278 (99%) subjects and all 190 (100%) subjects who completed the follow-up at 3 and 5 years, respectively, had NT titres ≥10. Likewise, all 275 of 278 (99%) and 188 of 190 (99%) subjects tested positive by ELISA at 3 and 5 years after the booster vaccination, respectively. Based on serological data, the interval for subsequent booster vaccinations with Encepur ® Children can be extended from 3 to 5 years after receiving primary vaccination and a first booster vaccination 12–18 months later.

Long-term persistence of tick-borne encephalitis antibodies in adults 5 years after booster vaccination with Encepur® Adults

Tick-borne encephalitis (TBE) is a potentially serious disease, especially in adults. There is no treatment available for TBE; supportive therapy may help to ease symptoms of the disease. Vaccination is the most effective method of preventing TBE disease and is recommended for those who live, work, or travel in TBE-endemic areas. Regular booster vaccinations are recommended every 3–5 years to maintain protection. Evidence from recent clinical studies suggests that TBE antibodies persist at high levels for longer than the current recommended intervals for TBE booster vaccination.The aim of this study was to evaluate the long-term persistence of TBE antibodies in adults after primary vaccination using a rapid schedule and a first booster dose of Encepur® Adults, an inactivated TBE vaccine. A total of 222 adults 19–51 years of age were invited for serological follow-up investigations 3 and 5 years following their first booster dose. High antibody titres were recorded throughout the follow-up period. Neutralization test (NT) titres ≥10 were noted in 99% of subjects 3 and 5 years after the first booster vaccination and 97% tested positive by enzyme-linked immunosorbent assay (ELISA). These results indicate that initially high levels of TBE antibodies following the first booster dose of the vaccine may lead to long-term persistence of TBE antibodies, confirming previous findings and suggesting it may be appropriate to extend the interval between booster doses from 3 to 5 years.

Advances in vaccination against tick-borne encephalitis

Tick-borne encephalitis (TBE) poses a growing health problem in many European countries and parts of Northern Asia. Thus, vaccination has been employed successfully for many years in endemic countries. Long-term experience gained from widespread use, however, prompted the development of improved vaccine formulations of the two licensed European TBE vaccines. Moreover, recent clinical trials also suggested the maintenance of high values of postvaccination neutralizing TBE antibodies for a longer period than expected; thus, also resulting in modifications with regards to immunization regimens. Recent advances in recombinant DNA technology have opened up future opportunities for developing novel live-attenuated vaccines against TBE virus and other flaviviruses. Animal experiments demonstrated safety and high immunogenicity profiles for these mutants; thus, making them promising vaccine candidates that will need to demonstrate a clear advantage if they are going to be alternatives to the traditional vaccines. Systematic TBE case monitoring by raising problem awareness, both inside and outside endemic regions, appears essential to provide evidence for a widely accepted TBE travel-vaccination recommendation in the future.

Antibody persistence following booster vaccination against tick-borne encephalitis: 3-Year post-booster follow-up

In order to evaluate the long-term immunity 2 and 3 years after booster vaccination against tick-borne encephalitis (TBE) following time intervals 3 years and longer since last TBE immunization, 195 (mean age 50.5+/-15.1 years) and 240 subjects (mean age 47.0+/-15.4 years), respectively, who had received a single booster dose in a preceding study, returned for a serological follow-up. Antibody concentrations were measured by neutralization test (NT) and ELISA. Protective TBE antibody levels (NT>or=10) were noted in 96% (187/195) of the subjects at year 2 and 97% (232/240) at year 3 post-booster. At both years, GMTs (NT) of all age groups were above detection limit (>or=2), showing GMT-NT of 54.5 (95% CI: 47.7-62.4) and 69.1 (95% CI: 60.7-78.6), respectively. GMTs were significantly lower in vaccinees>or=50 years of age (p<0.001 for both years). Comparison of GMTs at years 2 and 3 post-booster vaccination with pre-booster values revealed similar antibody titers at all three reading points. Besides an expected rapid decline of TBE antibodies shortly after booster administration, the kinetic curve also suggested maintenance of high values of neutralizing TBE antibodies for a period longer than expected, thus confirming the recent recommendations regarding the extension of TBE booster intervals.

Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN ®: Results of two large phase 3 clinical studies

A prospective, randomised, multicentre, single-blind phase 3 study was performed to assess the safety of a vaccination schedule consisting of two vaccinations (21–35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN ® “adults” (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur ®, with polygeline) (two lots) in healthy volunteers ( n = 3966) aged 16–65 years. The safety of the third vaccination with FSME-IMMUN ® “adults” (6 months after the first vaccination) was investigated in a follow-up study on the same population ( n = 3705) and TBE antibody titres were analysed pre- and post-vaccination in a subgroup of volunteers ( n = 564). Following the first vaccination, the overall incidence of fever (≥38.0 °C) was 0.8% in the FSME-IMMUN ® “adults” study group and 5.6% in the comparator study group; fever was mainly mild. The fever rate after the second vaccination was 0.6% and 0.5% in the two study groups, respectively. Local and systemic reactions after the first vaccination occurred with a lower frequency in the FSME-IMMUN ® “adults” study group than in the comparator group. Upon analysing the tolerability of the third vaccination with FSME-IMMUN ® “adults”, similar results were determined in both study groups of volunteers previously vaccinated with FSME-IMMUN ® “adults” or with the comparator vaccine. The immunogenicity results demonstrated similar seroconversion rates (as determined by ELISA or neutralization test) before and after the third vaccination in the FSME-IMMUN ® “adults” group and in the comparator group respectively. The results of both studies demonstrate that: (1) FSME-IMMUN ® “adults” is safe and highly immunogenic, (2) all five production lots of FSME-IMMUN ® “adults” were consistent with respect to a low rate of adverse events, (3) FSME-IMMUN ® “adults” induces considerably lower adverse reaction rates than the comparator vaccine after the first vaccination, and (4) two vaccinations with the comparator vaccine can be successfully followed by a third vaccination with FSME-IMMUN ® “adults”.