Safety of the Dengue Vaccine TAK-003 and Factors Associated with Adverse Events in Travellers from Non-Endemic Areas: A Real-World Prospective Multicentre Pharmacovigilance Cohort Study in Spain

IF 15.7 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Europe Pub Date : 2026-08-01 Epub Date: 2026-06-03 DOI:10.1016/j.lanepe.2026.101727

Daniel Camprubí–Ferrer, Cesc Bertran–Cobo, Lluís Valerio, Meritxell Saloni, Isabel González Nieto, Victoria López López, David Garcia, Elisabet Jurado, Maria Luisa Machado, Daniela Pérez–León, Sarai Cuevas Marín, Carme Subirà, Judit Villar–García, Dolores Herena García, Susana Nuria Ayala Cortés, Maria Sànchez Casado, Aina Gomila–Grange, Claudia Flores, Natalia Morales Llorente, Ester Górriz Hidalgo, José Muñoz

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引用次数: 0

Abstract

Background

TAK-003 is the first dengue vaccine licensed for endemic and non-endemic regions, but real-world safety data in non-endemic travel settings are scarce, particularly for older adults, people with comorbidities, and concomitant vaccinations.

Methods

We conducted a prospective multicentre pharmacovigilance study in eight Spanish travel clinics, enrolling travellers aged ≥4 years who received TAK-003 (January–December 2024). Participants were followed for adverse events (AEs) after each dose. Logistic regression models assessed associations of age, sex, comorbidities, prior flaviviral infection or vaccination history, and concomitant vaccination with risks of any, systemic, or local AEs.

Findings

Among 1028 participants (1851 TAK-003 doses), 998 (97.1%) completed ≥1 follow-up assessments; 587/998 (58.8%, 95% CI 55.7–61.8) reported AEs. After the first dose, 470/998 (47.1%, 44.0–50.2) reported AEs, most often injection site pain and swelling, headache, or malaise, declining to 235/679 (34.6%, 31.1–38.3) after the second dose. No serious AEs, anaphylaxis, or deaths occurred. Female sex was associated with any AEs (adjusted OR 1.83, 95% CI 1.42–2.37) and local AEs (1.89, 1.44–2.48). Prior dengue was associated with any (1.51, 1.07–2.14) and systemic AEs (1.73, 1.22–2.43). Concomitant flaviviral vaccination was associated with higher odds of systemic AEs (1.64, 1.18–2.28). Age ≥60 years and comorbidities were not associated with increased reactogenicity.

Interpretation

TAK-003 was well tolerated in travellers from non-endemic regions, with no serious AEs reported. Female sex, prior DENV infection, and flaviviral vaccine co-administration were associated with increased reactogenicity; older age, comorbidities, and non-flaviviral vaccine co-administration were not. These findings provide real-world evidence on tolerability of TAK-003 in travellers from non-endemic regions. Larger studies with extended follow-up are needed to better characterise uncommon and longer-term AEs.

Funding

No dedicated funding.

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来自非流行地区旅行者的登革热疫苗TAK-003的安全性和与不良事件相关的因素：西班牙一项真实世界前瞻性多中心药物警戒队列研究

背景：TAK-003是首个获得许可用于登革热流行和非流行地区的登革热疫苗，但在非流行旅行环境中的实际安全性数据很少，特别是对于老年人、合并症患者和伴随接种疫苗的安全性数据。方法：我们在8个西班牙旅行诊所进行了一项前瞻性多中心药物警戒研究，招募了年龄≥4岁并接受TAK-003治疗的旅行者（2024年1月至12月）。每次给药后随访参与者的不良事件（ae）。Logistic回归模型评估了年龄、性别、合并症、既往黄病毒感染或疫苗接种史以及伴随疫苗接种与任何系统性或局部ae风险的关系。结果：在1028名参与者（1851剂TAK-003）中，998名（97.1%）完成了≥1次随访评估；587/998 （58.8%, 95% CI 55.7-61.8）报告ae。第一次给药后，470/998例（47.1%,44.0-50.2）报告不良反应，最常见的是注射部位疼痛和肿胀、头痛或不适，第二次给药后下降到235/679（34.6%,31.1-38.3）。未发生严重不良反应、过敏反应或死亡。女性与任何ae（调整后OR 1.83, 95% CI 1.42-2.37）和局部ae（1.89, 1.44-2.48）相关。既往登革热与任何ae（1.51, 1.07-2.14）和全身ae（1.73, 1.22-2.43）相关。同时接种黄病毒疫苗与发生全身性不良反应的几率较高相关（1.64,1.18-2.28）。年龄≥60岁和合并症与反应原性增加无关。解释：TAK-003在来自非流行地区的旅行者中耐受性良好，未报告严重不良反应。女性、既往DENV感染和同时接种黄病毒疫苗与反应原性增加有关；年龄、合并症和非黄病毒疫苗的联合使用没有影响。这些发现为来自非流行地区的旅行者对TAK-003的耐受性提供了真实证据。需要更大规模的随访研究来更好地描述不常见的和长期的ae。资金：没有专门的资金。

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.