Immunogenicity and safety of the third booster dose of the inactivated Japanese encephalitis vaccine in Korean children: A prospective multicenter study

The immunization schedule for the inactivated Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12–24 months of age and three booster doses at 12 months after primary schedule and at 6 and 12 years of age. The aim of this study was to investigate immunogenicity and safety of the third booster dose of the inactivated JE vaccine, as well as the long-term immunogenicity of the second booster dose in Korean children. Healthy children aged 11–13 years, primed and given four doses of inactivated JE vaccines were included. All subjects received the third booster dose of the JE vaccine. Neutralizing antibody (NTAb) titers were assessed before and 4–6 weeks after vaccination using plaque reduction neutralization test (PRNT), and were considered to be protective at ≥ 1:10. Local and systemic adverse events were monitored for 4 weeks after vaccination. Before and after booster vaccination, all seroprotection rates were 100%. Geometric mean titer (GMT) showed a 6.05–fold increase, from 139.11 (95% CI: 110.76, 174.71) to 841.53 (95% CI, 714.25, 991.50). The local tolerability and systemic safety profiles were favorable, with no serious adverse events. In conclusion, the third booster dose of the inactivated JE vaccine was demonstrated to be safe and immunogenic in Korean children when administered according to the current immunization schedule.     

Immunogenicity of an inactivated Japanese encephalitis vaccine (JE-VAX) in humans over 20 years at USAMRIID: Using PRNT50 as an endpoint for immunogenicity

Two hundred and ninety-three subjects received a three-dose primary JE-VAX series and had post-primary shot 3 titers within 56 days at USAMRIID from 1985 to 2005. Overall, the PRNT50 primary response rate (titer of 1:10 or greater) was 269/293 (92%). Eighteen out of 19 subjects (95%) responded with adequate PRNT50 titer within 56 days after first JE-VAX boost. Primary PRNT50 responses to JE-VAX varied significantly in response rates and in geometric means (GMT) by vaccine lot. We recommend that future vaccine studies using PRNT as an immunologic endpoint include a coefficient of variation result alongside the GMT to assist in evaluating GMT results. For subjects who responded within 56 days of primary shot 3, 50% experienced a PRNT50 decline in titer to <1:10 at 805 days and a PRNT80 decline in titer to <1:10 at 355 days. Consequently, for individuals traveling to JE endemic areas, we recommend JE-VAX boost every 2 years and for individuals working with high titers of JE virus in the lab setting, we would recommend JE-VAX boost annually.     

Primary and booster immune responses to SA14-14-2 Japanese encephalitis vaccine in Korean infants.

Attenuated SA14-14-2 Japanese encephalitis (JE) vaccine has been administered safely and effectively to more than 100 million children in China since 1988 and recently, licensure of the vaccine in Korea has been sought. In the first clinical evaluation of the vaccine outside of China, we monitored side effects in 84 children and evaluated antibody responses to a single dose given as primary JE vaccination in 68 children, 1-3 years old (mean age 27 months). No significant adverse events were noted. Neutralizing antibodies (geometric mean titer [GMT] of 188) were produced in 96% of the 68 subjects. In 10 other children who previously had been immunized with two or three doses of inactivated JE vaccine, the booster administration of SA14-14-2 vaccine produced an anamnestic response in all, with a GMT of 3378. In a comparison group of 25 children previously immunized with two doses of inactivated vaccine, neutralizing antibody titers were detected in 16 (64%). Viral specific IgM was detected in nine primary vaccinees (13%) but in others, IgM may have declined to undetectable levels in the four week postimmunization sample. Live attenuated SA14-14-2 JE vaccine is a promising alternative to the only commercially available JE vaccine for national childhood immunization programs in Asia.     

Long-term immunogenicity of an initial booster dose of an inactivated,Vero cell culture-derived Japanese encephalitis vaccine (JE-VC) and the safety and immunogenicity of a second JE-VC booster dose in children previously vaccinated with an inactivated,mouse brain-derived Japanese encephalitis vaccine

BackgroundThis study was performed with the aim of determining the long-term immunogenicity of an inactivated, Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) and an inactivated, mouse brain-derived JE vaccine (JE-MB) after the 1st booster dose at 2 years of age, as well as the safety and immunogenicity of the 2nd booster dose of JE-VC at 6 years of age, in children primed and given a 1st booster dose of either JE-VC or JE-MB.MethodIn this multicenter, open-label clinical trial, the study population consisted of healthy Korean children (aged 6 years) who participated in the previous JE vaccine trial. All subjects were subcutaneously vaccinated once for the booster immunization with Boryung Cell Culture Japanese Encephalitis Vaccine® (JE-VC).ResultApproximately 4 years after the 1st booster dose of JE-VC, the seroprotection rate (SPR) and geometric mean titer (GMT) of the neutralizing antibody were 100% and 1113.8, respectively. In children primed and given a 1st booster dose of JE-MB, the SPR and GMT were 88.5% and 56.3, respectively. After the 2nd booster dose of JE-VC, all participants primed and given a 1st booster dose of either JE-MB or JE-VC were seroprotective against JE virus. The GMT of the neutralizing antibody was higher in children primed and given a 1st booster dose of JE-VC (8144.1) than in those primed and given a 1st booster dose of JE-MB (942.5) after the vaccination (p < 0.001). In addition, the 2nd booster dose of JE-VC showed a good safety profile with no serious vaccine-related adverse events.ConclusionThe 1st booster dose of JE-VC and JE-MB showed long-term immunogenicity of at least 4 years, and the 2nd booster dose of JE-VC showed a good safety and immunogenicity profile in children primed and given a 1st booster dose of either JE-VC or JE-MB.ClinicalTtrials.gov Identifier: NCT02532569     

Immune response at 12–23 months following a single dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine

BackgroundJapanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12–23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series.MethodsWe obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12–23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5.ResultsThe GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63–90) and in previously JE vaccine-naïve persons was 12 (95% CI 11–14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0–7.7), satisfying the criterion for non-inferiority.ConclusionsOne JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1–2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs.     

Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: A single-blind,randomized, controlled Phase 3 study

In travellers often several pre-departure immunizations are indicated, thus data are needed about possible interactions between vaccines. This Phase 3 study investigated the immunogenicity and safety of IC51 (JE vaccine) and HAVRIX^®1440 (hepatitis A vaccine) when administered alone or concomitantly to healthy subjects. The immune response was compared between single and concomitant vaccination in terms of geometric mean titre (GMT) and seroconversion rate (SCR) on Days 28 and 56. Immunogenicity was comparable for the 2 vaccines whether given together or separately which suggests that travellers to such regions could receive the vaccinations concomitantly.     

Immune responses of anti-HAV in children vaccinated with live attenuated and inactivated hepatitis A vaccines

The immunogenicity of a live attenuated HAV vaccine and an inactivated HAV vaccine was compared.Altogether 117 children were vaccinated with either the inactivated or the live attenuated vaccine. Children were bled at months 1, 6, 7, 12 and 24, and the anti-HAV total IgG antibody and IgG subclass profile were assessed. In both vaccinated groups, the geometric mean titer (GMT) of anti-HAV peaked 7 months after the initial dose and declined during the following months. The IgG subclass profiles in both vaccinated groups were highly restricted to IgG1 and IgG3. Both vaccines have been shown highly effective in preventing viral hepatitis A in former studies.     

Immunogenicity and safety of the inactivated Japanese encephalitis vaccine IXIARO® in elderly subjects: Open-label,uncontrolled, multi-center,phase 4 study

BackgroundIXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available.ObjectivesTo evaluate safety and immunogenicity of IXIARO in elderly subjects.MethodsOpen-label, single arm, multi-centered study. Two-hundred subjects with good general health, including adequately controlled chronic conditions, received two doses of IXIARO®, 28 days apart. Protective levels of antibodies were tested 42 days after the second dose. Systemic and local adverse events (AEs) were solicited for 7 days after each dose, unsolicited AEs were collected up to day 70 and in a phone call at month 7.Summary of resultsSubjects were aged 64–83 years (median 69.0 years). Nineteen percent of subjects had serious or medically attended AEs up to Day 70 (primary endpoint), none of them causally linked to IXIARO. Solicited local AEs were reported by 33.5% (most common: local tenderness) and solicited systemic AEs by 27% (most common: headache) of subjects. The seroprotection rate was 65% with a geometric mean titre (GMT) of 37. Subjects with tick borne encephalitis (TBE) vaccinations in the past 5 years (N = 29) had a SCR of 90% and GMT of 65.ConclusionsIXIARO is generally well tolerated in the elderly, and the safety profile is largely comparable with younger adults. SCR and GMT are lower compared to younger adults, but SCR is in the range reported in elderly for other vaccines e.g. against TBE, hepatitis-A virus (HAV)/hepatitis-B virus (HBV), influenza. The differences in SCR and GMT from younger to elderly adults were in the range of other vaccines.Duration of protection is uncertain in older persons, therefore a booster dose (third dose) should be considered before any further exposure to JE virus.     

Recent immunization against measles does not interfere with the sero-response to yellow fever vaccine

In order to determine whether previous measles vaccination interferes with the sero-response to yellow fever vaccine, 294 children at nine months of age were randomly assigned to immunization with yellow fever vaccine at different time intervals after measles vaccination. The seroconversion rate (SCR) and the log10 geometric mean titer (GMT) for 17 DD yellow fever vaccine at different intervals after Schwarz measles vaccination were: 1-6 days: SCR = 44/57 = 77%; GMT = 4.57; 7-13 days: SCR = 36/53 = 68%; GMT = 4.46; 14-21 days: SCR = 55/65 = 85%; GMT = 4.46; 22-27 days: SCR = 41/54 = 76%; GMT = 4.41 and >28 days: SCR = 52/65 = 80%; GMT = 4.24 (p > 0.05). We conclude that recent immunization against measles does not interfere with the sero-response to yellow fever vaccine.     

Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine

Background

There are no data on the use of inactivated Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) as a booster among individuals who previously received inactivated mouse brain-derived JE vaccine (JE-MB).

Methods

Military personnel who received ≥3 doses of JE-MB or were JE vaccine-naïve were vaccinated with 2 doses of JE-VC on days 0 and 28. Serum neutralizing antibodies were measured pre-vaccination and 28 days after each dose. Non-inferiority was evaluated for seroprotection rate and geometric mean titer (GMT) between previously vaccinated participants post-dose 1 and vaccine-naïve participants post-dose 2.

Results

Fifty-three previously vaccinated and 70 JE vaccine-naïve participants were enrolled. Previously vaccinated participants had significantly higher GMTs pre-vaccination, post-dose 1, and post-dose 2. Seroprotection rates among previously vaccinated participants post-dose 1 (44/44, 100%) were noninferior to those achieved in previously naïve participants post-dose 2 (53/57, 93%). The GMT was significantly higher in previously vaccinated participants post-dose 1 (GMT 315; 95% CI 191–520) compared to previously naïve participants post-dose 2 (GMT 79; 95% CI 54–114).

Conclusions

Among military personnel previously vaccinated with ≥3 doses of JE-MB, a single dose of JE-VC adequately boosts neutralizing antibody levels and provides at least short-term protection. Additional studies are needed to confirm these findings in other populations and determine the duration of protection following a single dose of JE-VC in prior recipients of JE-MB.     

A 3-year follow-up of antibody response in HIV-infected children with immune recovery vaccinated with inactivated Japanese encephalitis vaccine

Among HIV-infected children who had immune recovery after received antiretroviral therapy (ART), good responses to revaccination with childhood vaccines have been observed. However, the rate of long-term persistence of antibody response remains unknown. The objective of this study is to determine whether HIV-infected children still have protective antibody against Japanese encephalitis virus (JE) 3 years after receiving revaccination with two doses of inactivated JE vaccine. Plasma JE neutralizing antibody titer was determined by a plaque reduction neutralization assay. An antibody titer of more than 1:10 was defined as being protective. Fifty HIV-infected children with a mean age of 10.3 years (SD 2.2) and mean CD4 percentage of 25 (SD 5) were revaccinated with two doses of inactivated JE vaccine. Forty-three children had been followed-up for 3 years. The JE neutralizing antibody at 1 month and 3 years after revaccination were detected among 38 (88%) and 35 (81%) children, respectively. The geometric means titer significantly dropped from of 306 (min 13–max 163,617) to 106 (min 11–max 4645). This data show that the majority of HIV-infected children had persistent antibody 3 years after revaccination. JE revaccination in HIV-infected children with immune recovery after ART should be carried out in endemic areas.     

Comparison of a single,high-dose vaccination regimen to the standard regimen for the investigational Japanese encephalitis vaccine,IC51: A randomized,observer-blind,controlled Phase 3 study

The standard administration of the investigational Japanese encephalitis vaccine IC51 is 2 doses of 6 μg with a 28-day interval. This study investigated the immunogenicity of a single-immunization, high-dose regimen (1 × 12 μg) compared to the 2-injection, standard regimen to determine the immune response that one, high-dose injection can confer. The single, high-dose regimen resulted in about 60% seroconversion rate (SCR) at 10 days after administration, but it did not reach the almost 100% SCR achieved by the 2-dose standard administration at Day 35. The standard regimen conferred essentially 100% seroconversion already 7 days after the second immunization.     

A purified inactivated Japanese encephalitis virus vaccine made in Vero cells

A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.     

Needle-free jet injection of small doses of Japanese encephalitis DNA and inactivated vaccine mixture induces neutralizing antibodies in miniature pigs and protects against fetal death and mummification in pregnant sows

Japanese encephalitis (JE) virus causes abortion and stillbirth in swine, and encephalitis in humans and horses. We have previously reported that immunogenicity of a DNA vaccine against JE was synergistically enhanced in mice by co-immunization with a commercial inactivated JE vaccine (JEVAX) under a needle-free injection system. Here, we found that this immunization strategy was also effective in miniature pigs. Because of the synergism, miniature pigs immunized twice with a mixture of 10 μg of DNA and a 1/100 dose of JEVAX developed a high neutralizing antibody titer (1:190 at 90% plaque reduction assay). Even using 1 μg of DNA, 3 of 4 pigs developed neutralizing antibodies. Following challenge, all miniature pigs with detectable neutralizing antibodies were protected against viremia. Pregnant sows inoculated with 10 or 1 μg of DNA mixed with JEVAX (1/100 dose) developed antibody titers of 1:40–1:320. Following challenge, fetal death and mummification were protected against in DNA/JEVAX-immunized sows.     

Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine

The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.     

Recommendations for use of a booster dose of inactivated vero cell culture-derived Japanese encephalitis vaccine: advisory committee on immunization practices, 2011

Japanese encephalitis (JE) virus, a mosquito-borne flavivirus, is an important cause of encephalitis in Asia with a case fatality rate of 20%--30% and neurologic or psychiatric sequelae in 30%--50% of survivors (1). Travelers to JE-endemic countries and laboratory personnel who work with infectious JE virus are at potential risk for JE virus infection. In 2010, CDC's Advisory Committee on Immunization Practices (ACIP) updated recommendations for prevention of JE. The updated recommendations included information on use of a new inactivated, Vero cell culture--derived JE vaccine (JE-VC [manufactured as Ixiaro]) that was licensed in the United States in 2009. Data on the need for and timing of booster doses with JE-VC were not available when the vaccine was licensed. This report summarizes new data on the persistence of neutralizing antibodies following primary vaccination with JE-VC and the safety and immunogenicity of a booster dose of JE-VC. The report also provides updated guidance to health-care personnel regarding use of a booster dose of JE-VC for U.S. travelers and laboratory personnel. ACIP recommends that if the primary series of JE-VC was administered >1 year previously, a booster dose may be given before potential JE virus exposure.     

Immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive): a double-blind, randomized and controlled trial

Immunization is considered as the most effective way for the prophylaxis of hepatitis A virus (HAV) infection. This study aimed to evaluate the immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive) in healthy children. A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers aged from 1 to 8 years. Total 400 subjects were enrolled and assigned into four groups, receiving one of the three lots of Healive or an established control vaccine. The vaccination was two-dose regimen with 6 months apart. Anti-HAV titers were determined at the 1st, 6th and 7th month. The results showed that Healive was highly immunogenic in children with 100% seroconversion rate (SR) and 3237-3814 mIU/ml geometry mean titer (GMT) 1 month after the second dose. The immunogenicity of Healive was statistically higher than that of the control vaccine with respect to GMT and SR (P=0.037 to P<0.001). Both Healive and control vaccine were well tolerated with 1-5% incidence of overall adverse reactions (P>0.298). Severe adverse reaction was not reported. Both SRs (1, 6 and 7 months) and GMTs (1 and 7 months) in subjects receiving one of the three consecutive lots of Healive had not statistical difference (P=0.114-0.710), suggesting that Healive was well consistent. The immune responses in younger children (1-3 years) and older children (4-8 years) were similar to each other (P=0.187-0.963). The present study indicated that Healive was greatly consistent between production lots, well tolerated and highly immunogenic in children, which made the preservative-free inactivated hepatitis A vaccine well suitable for inclusion in the routine programme of children vaccination.     

孩尔来福甲型肝炎灭活疫苗0,12个月免疫程序研究

目的　对孩尔来福 (HealiveR○)甲型肝炎 (甲肝 )灭活疫苗的安全性、免疫原性及适宜儿童的剂量进行研究。方法　在某山区两个农村筛选 4～ 10岁甲肝病毒抗体 (抗 HAV)阴性的 85名易感儿童。以自然村随机分为两组 ,按 0 ,12个月免疫程序分别接种北京科兴生物制品有限公司生产的每剂 2 50U 0 .5ml和 50 0U 1ml甲肝灭活疫苗 ,观察免疫后局部反应和全身反应 ,检测初次免疫 (初免 )后 2 1天、12个月及全程免疫后 1个月抗 HAV阳转率和抗体几何平均滴度 (GMT )。结果　两组均未见严重局部反应和全身反应 ;2 50U 0 .5ml组和 50 0U 1ml组初免后 2 1天 ,抗 HAV阳转率分别为94.4%和 10 0 .0 % ,GMT分别为 195mIU ml和 3 70mIU ml ;初免后 12个月抗 HAV全部阳转 ,GMT分别达 3 61mIU ml和 456mIU ml(P >0 .0 5) ;全程免疫后 1个月 ,GMT分别达 14 893mIU ml和2 1696mIU ml。结论　孩尔来福甲肝灭活疫苗的安全性和免疫原性好 ;每剂 2 50U 0 .5ml适宜儿童 ;0 ,12个月免疫程序更适宜中国儿童     

Persistence of antibodies six years after booster vaccination with inactivated vaccine against Japanese encephalitis

BackgroundJapanese Encephalitis (JE) virus occurs in wide regions of Asia with over 3 billion people living in areas at risk for JE. An estimated 68,000 clinical cases of JE occur every year, and vaccination is the most effective prophylactic measure. One internationally licensed vaccine containing the inactivated JE virus strain SA₁₄-14-2 is Ixiaro^® (Valneva, Austria). According to recommendations, basic immunization consists of vaccinations on day 0, day 28, and a booster dose 12–24 months later. Protection in terms of neutralizing antibody titers has been assessed up to 12 months after the third dose of the vaccine. The current investigation was designed to evaluate antibody decline over time and to predict long-term duration of seroprotection after a booster dose.MethodIn a preceding trial, volunteers received basic immunization (day 0, day 28) and one booster dose against JE 15 months later. A follow up blood draw 6 years following their booster dose was carried out in 67 subjects. For antibody testing, a 50% plaque reduction neutralization test (PRNT₅₀-test) was used. PRNT₅₀ values of 10 and above are surrogate levels of protection according to WHO standards.ResultSeventy-six months following the booster dose, 96% of the tested subjects had PRNT₅₀ titers of 10 or higher. Geometric mean titer (GMT) was 148 (95% CI confidence interval: 107–207). Antibody titers were lower in volunteers 50 years of age and older. Vaccination history against other flaviviruses (yellow fever or tick borne encephalitis) did not significantly influence PRNT₅₀ titers. A two-step log-linear decline model predicted protection against JE of approximately 14 years after the booster dose.ConclusionSix years after a booster dose against JE, long-term protection could be demonstrated. According to our results, further booster doses should be scheduled 10 years following the first booster dose.