Antigen dependent adverse reactions and seroconversion of a tick-borne encephalitis vaccine in children. A new vaccine against tick-borne encephalitis: initial trial in man including a dose-response study. Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN: results of two large phase 3 clinical studies. Tick-born encephalitis (TBE) vaccination in children: advantage of the rapid immunization schedule (i.e., days 0, 7, 21). [A cultured concentrated inactivated vaccine against tick-borne encephalitis studied during the immunization of children and adolescents]. Tick-borne encephalitis: development of a paediatric vaccine. A controlled, randomized, double-blind and multicentre study. A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens. Randomized, phase II dose-finding studies of a modified tick-borne encephalitis vaccine: evaluation of safety and immunogenicity. Tick-borne encephalitis (TBE) vaccination: applying the most suitable vaccination schedule.
Two randomized, double blind dose comparison studies were conducted in 595 children in Austria and Germany with an albumin-free and thiomersal-free tick-borne encephalitis (TBE) vaccine. Vaccinated subjects of an age between 6 months and 12 years randomly assigned received either the full adult dose or half the adult dose. Results from vaccinated children under 1 year of age at the time of the first vaccination (159 subjects) showed an age dependent immune response. There were significantly fewer adverse systemic events (e.g. fever reactions). In children who received only half the adult dose, while seroconversion was not significantly different (93% versus 98%) after the second vaccination, and 100% for both groups after the third vaccination. Based on these results, it is recommended to vaccinate children between the ages of 1 and 12 years with half the adult dose. A new vaccine against tick-borne encephalitis was investigated in 56 healthy volunteers randomized for five different doses of antigen in a comparative group trial. Good tolerability and high immunogenicity were found using three different antibody test systems. The dose response study revealed that there was a strong relationship between the amount of antigen administered and the antibody response over the range of 0.03-3.0 micrograms antigen per dose. 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 (> or =38.0 degrees 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". Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N = 73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N = 139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N = 82, vaccination on Days 0, 7 and 21). Antibody titers as measured by neutralization-test (NT) and ELISA were determined on Days 0, 42, 180, 300, and 321. The demographic data of the study groups were similar. Most subjects (97%-100%) reached an NT titer of at least 1:10 on Day 42. On Day 42, the highest NT geometric mean titers (GMTs) were reached in Group C. In Group C and Group M, titers declined up to Day 300. Until Day 300, the highest NT-GMTs were maintained in Group R, notably without a decline compared to Day 42. Group M reached titers similar to Group R on Day 42, but these titers declined by 50% up to Day 180. Similar to the NT, on Day 42 highest geometric mean concentrations (GMCs) as measured by ELISA across all groups were reached in Group C. In all groups, titers declined until Day 300. On Day 300, GMC ELISA of Group R was higher compared to Group C and Group M. To conclude, the rapid immunization schedule in children not only provides fast protection but also leads to stable titers as measured by NT for at least 300 days after vaccination. The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents. A total of 522 children between 18 months and 14 years and 191 adults between 18 and 60 years were vaccinated with TBE-vaccine according to an abbreviated schedule (0, 7, 21). The aim of the study was to investigate whether reducing the amount of antigen in the vaccination for children would preserve an adequate immune response and decrease the rate of side-effects. Efficacy was determined on the extent to which children, vaccinated with the low doses (0.4 microgram or 0.75 microgram), reacted by developing antibodies in the same way as adults treated with the approved dose of 1.5 micrograms (equivalence of titres). The titres obtained in the children with the two lower doses were equivalent to those in the adults obtained with the standard dose. Titres decreased in the children with increasing age. Children older than 12 years in the approved dosage group had the same median titres as adults. The frequency of side-effects in the two lower dose groups, especially raised temperature, was markedly reduced. Whereas 30.1% of the children vaccinated with the approved dose had raised temperature higher than 38 degrees C only 18.8% and 18.4%, respectively, of the children vaccinated with the lower doses developed such temperatures. This improved tolerance in terms of raised temperature was also reflected in the other general reactions such as tiredness, joint pain or headache. A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS) Two clinical studies were conducted to identify the optimal dose of a modified tick-borne encephalitis (TBE) vaccine (FSME-IMMUN "new") in adults. A prospective, randomised, phase II, double-blind dose-finding study with the FSME-IMMUN "new" vaccine was performed in volunteers aged 16-65 years (n=405) to evaluate the immunogenicity and safety of two vaccinations with three vaccine doses (0.6, 1.2 and 2.4microg antigen). The safety and immunogenicity of the third vaccination were investigated in a follow-up study on the same study population. Antibody response to vaccination was assessed by enzyme-linked immunosorbent assay (ELISA) and, after the third vaccination, by neutralisation test (NT). Seroconversion rates (ELISA) in the different dose groups (0.6, 1.2 and 2.4 microg) were 85.1, 96.2 and 97.0%, respectively, after the second vaccination, which 73% of the volunteers received only 21 days after the first vaccination. Seroconversion rates after the third vaccination were 96, 99.2 and 100% (ELISA) as well as 77, 93 and 96.6% (NT) with the 0.6, 1.2 and 2.4 microg doses, respectively. No unexpected AEs or vaccine-related serious adverse events (SAE) were observed during either study. Local and systemic reactions were mainly mild and not dose-dependent, with an overall fever rate of <1% after the first vaccination. The 2.4 microg dose is the optimal dose for the FSME-IMMUN "new" preparation in adults, as it was found to: (1) be non-inferior to the 1.2 microg dose with respect to fever rate after the first vaccination; (2) induce the highest seroconversion rate; and (3) be well-tolerated with respect to local and systemic reactions. The results of both studies demonstrate that the FSME-IMMUN "new" vaccine is safe and highly immunogenic in adults. Tick-borne encephalitis (TBE) is caused by an arthropod-borne virus, belonging to the family of Flaviviridae. In case of disease, which can lead to neurological sequelae or even fatal outcomes, only symptomatic treatment is available. TBE can be prevented by vaccination. Various primary immunization schedules have been developed. To identify the most suitable schedule, the present randomised, controlled study was designed to provide data on the immune response elicited by four different immunization schedules obtained by ELISA and by neutralization test (NT). A total of 398 healthy subjects aged > or =12 years were randomised to vaccination according to either the rapid schedule (Group R, vaccination on days 0, 7 and 21), the conventional schedule (Group C, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M, vaccination on days 0, 21 and 300) or the accelerated conventional schedule (Group A, vaccination on days 0, 14 and 300). Within 3 weeks (i.e. by day 21) antibody levels were higher in Group R and Group A than in Group M and Group C. Group R and Group C both had higher titres on days 42, 180 and 300, than Group A and Group M. The rapid schedule thus combines the advantages of fast protection and of high titres over the observation period of 300 days.
Tick-borne encephalitis vaccines appear to be highly immunogenic, but the relationship between seroconversion and clinical protection has not been established. Although adverse effects were commonly reported, none were serious or life threatening.