Abstract：
BACKGROUND: Tick-borne encephalitis (TBE) virus infects the central nervous system and may lead to severe neurological complications or death. This study assessed immunogenicity, safety, and tolerability of TBE vaccine in Japanese participants 1 year of age and older.
METHODS: This phase 3, multicenter, single-arm, open-label study was conducted in Japanese adult (≥ 16 years) and pediatric (1-< 16 years) populations. Participants received a single 0.5-mL (adult) or 0.25-mL (pediatric) dose of TBE vaccine at each of 3 visits. The primary endpoint was the proportion of participants who were seropositive (neutralization test [NT] titer ≥ 1:10) 4 weeks after Dose 3. Secondary and exploratory endpoints included NT seropositivity rates 4 weeks after Dose 2, immunoglobulin G (IgG) seropositivity 4 weeks after Doses 2 and 3, NT geometric mean titers (GMTs), IgG geometric mean concentrations (GMCs), and geometric mean fold rises. Primary safety endpoints were frequencies of local reactions, systemic events, adverse events (AEs), and serious AEs.
RESULTS: Among 100 adult and 65 pediatric participants, 99.0 % and 100.0 % completed the study, respectively. NT seropositivity was achieved in 98.0 % adult and 100.0 % pediatric participants after Dose 3; seropositivity after Dose 2 was 93.0 % and 92.3 %, respectively. In both age groups, IgG seropositivity was ≥ 90.0 % and ≥ 96.0 % after Doses 2 and 3, respectively; GMTs and GMCs were highest 4 weeks after Dose 3. Reactogenicity events were generally mild to moderate in severity and short-lived. AEs were reported by 15.0 % (adult) and 43.1 % (pediatric) of participants. No life-threatening AEs, AEs leading to discontinuation, immediate AEs, related AEs, or deaths were reported. No serious AEs were considered related to TBE vaccine.
CONCLUSIONS: TBE vaccine elicited robust immune responses in Japanese participants 1 year of age and older. The 3-dose regimen was safe and well tolerated, and findings were consistent with the known safety profile of this TBE vaccine.
RESULTS: gov: NCT04648241.
METHODS: This phase 3, multicenter, single-arm, open-label study was conducted in Japanese adult (≥ 16 years) and pediatric (1-< 16 years) populations. Participants received a single 0.5-mL (adult) or 0.25-mL (pediatric) dose of TBE vaccine at each of 3 visits. The primary endpoint was the proportion of participants who were seropositive (neutralization test [NT] titer ≥ 1:10) 4 weeks after Dose 3. Secondary and exploratory endpoints included NT seropositivity rates 4 weeks after Dose 2, immunoglobulin G (IgG) seropositivity 4 weeks after Doses 2 and 3, NT geometric mean titers (GMTs), IgG geometric mean concentrations (GMCs), and geometric mean fold rises. Primary safety endpoints were frequencies of local reactions, systemic events, adverse events (AEs), and serious AEs.
RESULTS: Among 100 adult and 65 pediatric participants, 99.0 % and 100.0 % completed the study, respectively. NT seropositivity was achieved in 98.0 % adult and 100.0 % pediatric participants after Dose 3; seropositivity after Dose 2 was 93.0 % and 92.3 %, respectively. In both age groups, IgG seropositivity was ≥ 90.0 % and ≥ 96.0 % after Doses 2 and 3, respectively; GMTs and GMCs were highest 4 weeks after Dose 3. Reactogenicity events were generally mild to moderate in severity and short-lived. AEs were reported by 15.0 % (adult) and 43.1 % (pediatric) of participants. No life-threatening AEs, AEs leading to discontinuation, immediate AEs, related AEs, or deaths were reported. No serious AEs were considered related to TBE vaccine.
CONCLUSIONS: TBE vaccine elicited robust immune responses in Japanese participants 1 year of age and older. The 3-dose regimen was safe and well tolerated, and findings were consistent with the known safety profile of this TBE vaccine.
RESULTS: gov: NCT04648241.
摘要：
背景：蜱传脑炎（TBE）病毒感染中枢神经系统，并可能导致严重的神经系统并发症或死亡。这项研究评估了免疫原性，安全,1岁及以上日本参与者的TBE疫苗耐受性。
方法：此阶段3，多中心，单臂,在日本成人(≥16岁)和儿童(1-<16岁)人群中进行了开放标签研究.参与者在3次访问中每次接受单次0.5mL（成人）或0.25mL（儿科）剂量的TBE疫苗。主要终点是剂量3后4周血清阳性（中和试验[NT]滴度≥1:10）的参与者比例。次要和探索性终点包括剂量2后4周的NT血清阳性率，剂量2和3后4周的免疫球蛋白G（IgG）血清阳性率，NT几何平均滴度（GMT），IgG几何平均浓度（GMC），几何平均倍数上升。主要的安全终点是局部反应的频率，系统性事件,不良事件（AE），严重的AE。
结果：在100名成人和65名儿科参与者中，99.0%和100.0%完成了研究，分别。剂量3后，98.0%的成人和100.0%的儿科参与者达到NT血清阳性；剂量2后的血清阳性为93.0%和92.3%，分别。在这两个年龄组中，剂量2和3后IgG血清阳性率分别≥90.0％和≥96.0％；剂量3后4周GMT和GMC最高。反应性事件的严重程度通常为轻度至中度，持续时间短。15.0%（成人）和43.1%（儿童）的参与者报告了不良事件。没有危及生命的AE,导致停药的不良事件，即时AE，相关AE，或报告死亡。没有严重的AE被认为与TBE疫苗有关。
结论：TBE疫苗在1岁及以上的日本参与者中引发了强烈的免疫反应。3-剂量方案是安全和良好的耐受性，研究结果与该TBE疫苗的已知安全性一致.
结果：gov：NCT04648241。
方法：此阶段3，多中心，单臂,在日本成人(≥16岁)和儿童(1-<16岁)人群中进行了开放标签研究.参与者在3次访问中每次接受单次0.5mL（成人）或0.25mL（儿科）剂量的TBE疫苗。主要终点是剂量3后4周血清阳性（中和试验[NT]滴度≥1:10）的参与者比例。次要和探索性终点包括剂量2后4周的NT血清阳性率，剂量2和3后4周的免疫球蛋白G（IgG）血清阳性率，NT几何平均滴度（GMT），IgG几何平均浓度（GMC），几何平均倍数上升。主要的安全终点是局部反应的频率，系统性事件,不良事件（AE），严重的AE。
结果：在100名成人和65名儿科参与者中，99.0%和100.0%完成了研究，分别。剂量3后，98.0%的成人和100.0%的儿科参与者达到NT血清阳性；剂量2后的血清阳性为93.0%和92.3%，分别。在这两个年龄组中，剂量2和3后IgG血清阳性率分别≥90.0％和≥96.0％；剂量3后4周GMT和GMC最高。反应性事件的严重程度通常为轻度至中度，持续时间短。15.0%（成人）和43.1%（儿童）的参与者报告了不良事件。没有危及生命的AE,导致停药的不良事件，即时AE，相关AE，或报告死亡。没有严重的AE被认为与TBE疫苗有关。
结论：TBE疫苗在1岁及以上的日本参与者中引发了强烈的免疫反应。3-剂量方案是安全和良好的耐受性，研究结果与该TBE疫苗的已知安全性一致.
结果：gov：NCT04648241。
