BACKGROUND Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019. METHODS We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype. RESULTS Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively). CONCLUSIONS TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).

中文翻译：

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四价登革热疫苗对健康儿童和青少年的疗效。

背景 登革热是一种蚊子传播的病毒性疾病，在 2019 年被世界卫生组织指定为全球健康的十大威胁。方法 我们提供了正在进行的四价登革热候选疫苗（TAK- 003）在该病流行的亚洲和拉丁美洲地区。4 至 16 岁的健康儿童和青少年以 2:1 的比例（根据年龄类别和地区分层）随机分配接受两剂疫苗或安慰剂，间隔 3 个月。通过血清型特异性逆转录酶聚合酶链反应对出现发热性疾病的参与者进行病毒学确诊的登革热检测。主要终点是疫苗在预防由任何登革热病毒血清型引起的经病毒学证实的登革热方面的总体效力。结果 在接受了至少一剂疫苗或安慰剂的 20,071 名参与者（安全人群）中，19,021 名 (94.8%) 接受了两种注射，并被纳入符合方案分析。疫苗在安全人群中的总体效力为 80.9%（95% 置信区间 [CI]，75.2 至 85.3；疫苗组每 13,380 人中有 78 例 [每 100 人年 0.5 例]，而疫苗组每 6687 人中有 199 例 [每 100 人中有 2.5 例]人年]在安慰剂组）。在符合方案分析中，疫苗功效为 80.2%（95% CI，73.3 至 85.3；疫苗组有 61 例经病毒学确诊的登革热病例，而安慰剂组有 149 例病例），对导致住院的登革热的疗效为 95.4% （95% CI，88.4 至 98.2；疫苗组 5 次住院，安慰剂组 53 次住院）。计划的探索性分析涉及 27。基线时血清反应阴性的符合方案人群中有 7% 的疫苗效力为 74.9%（95% CI，57.0 至 85.4；疫苗组有 20 例经病毒学证实的登革热病例，安慰剂组有 39 例）。疗效趋势因血清型而异。疫苗组和安慰剂组的严重不良事件发生率相似（分别为 3.1% 和 3.8%）。结论 TAK-003 在疾病流行的国家对有症状的登革热有效。（由 Takeda Vaccines 资助；TIDES ClinicalTrials.gov 编号，NCT02747927。）疫苗组和安慰剂组的严重不良事件发生率相似（分别为 3.1% 和 3.8%）。结论 TAK-003 在疾病流行的国家对有症状的登革热有效。（由 Takeda Vaccines 资助；TIDES ClinicalTrials.gov 编号，NCT02747927。）疫苗组和安慰剂组的严重不良事件发生率相似（分别为 3.1% 和 3.8%）。结论 TAK-003 在疾病流行的国家对有症状的登革热有效。（由 Takeda Vaccines 资助；TIDES ClinicalTrials.gov 编号，NCT02747927。）