1-Year follow-up evaluation of TAK-003 dengue vaccine effectiveness against symptomatic disease and hospitalisation in adolescents during the 2024-2025 outbreak in São Paulo, Brazil: a test-negative case-control study.
Lisany Krug Mareto, Thiago Sanches Brumatti, Roberto Dias de Oliveira, Patricia Vieira da Silva, Edinéia Ribeiro Dos Santos, Tatiana Lang D'Agostini, Regiane A Cardoso De Paula, Natalie E Dean, Albert I Ko, Derek A T Cummings, Jason R Andrews, Matt D T Hitchings, Otavio Ranzani, Julio Croda
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引用次数: 0
Abstract
Background: Dengue is a growing global health threat. Our initial evaluation of the TAK-003 dengue vaccine in adolescents during the 2024 outbreak in São Paulo State, Brazil, showed short-term protection but suggested possible effectiveness waning after 90-days of the first dose, and had limited power to estimate second-dose effectiveness against hospitalisation. We evaluated 1-year vaccine effectiveness against symptomatic, virologically confirmed dengue and dengue hospitalisation in adolescents during 2024-2025, when DENV-1 and DENV-2 predominated in 2024 followed by increasing DENV-3 transmission in 2025.
Methods: We did a test-negative case-control study among adolescents aged 10-15 years in São Paulo State between Feb 20, 2024, and Dec 31, 2025. We extracted individual-level information on demographic characteristics, comorbidities, dengue testing, dengue vaccination, hospitalisation, and death during the study period from the national surveillance databases for dengue (SINAN-Dengue; compulsory notification) and the São Paulo State Secretary of Health vaccination registry (Rede Nacional de Dados em Saúde) on Feb 4, 2026. Cases were defined as acute febrile illness episodes with virologically confirmed dengue, as detected by NS1 antigen or RT-PCR testing within 5 days of symptom onset. Controls were test-negative acute febrile illness episodes. Surveillance data were linked to the state vaccination registry. Vaccine effectiveness after one or two TAK-003 doses was estimated with mixed-effects logistic regression.
Findings: We analysed 166,390 tests: 65,365 from cases and 101,025 from controls. Vaccine effectiveness against symptomatic dengue was 59.2% (95% CI 56.1-62.0) after one dose and 73.1% (69.1-76.6) after two doses. Against dengue hospitalisation, effectiveness was 74.6% (62.7-82.7) after one dose and 87.9% (73.0-94.6) after two doses. One-dose protection against symptomatic disease showed no evidence of waning over 1-year follow-up: effectiveness was 73.8% (64.7-80.6) at 270-364 days and 76.8% (59.3-86.8) at 365 days or more. Two-dose protection remained stable to 1 year (74.6%, 95% CI 59.0-84.2, at 270-365 days). Findings were robust in sensitivity analyses and comparable during increased DENV-3 circulation.
Interpretation: Our findings show that TAK-003 demonstrated sustained 1-year protection against symptomatic dengue and dengue hospitalisation in adolescents during a large outbreak. Notably, a single dose showed sustained effectiveness without evidence of waning over 1 year, generating an important hypothesis regarding dose reduction that warrants continued long-term observational evaluation. A second dose provided optimal protection, particularly against hospitalisation. These findings reinforce the importance of dengue vaccination as a public health measure.
Funding: National Council for Scientific and Technological Development.
背景：登革热是一种日益严重的全球健康威胁。我们在2024年巴西圣保罗州暴发期间对青少年接种TAK-003登革热疫苗的初步评估显示出短期保护作用，但表明首次接种90天后有效性可能减弱，并且估计第二次接种对住院治疗的有效性的能力有限。我们评估了2024-2025年期间青少年对有症状的、病毒学确诊的登革热和登革热住院治疗的1年疫苗有效性，当时DENV-1和DENV-2在2024年占主导地位，随后DENV-3在2025年传播增加。方法：我们在2024年2月20日至2025年12月31日期间对圣保罗州10-15岁的青少年进行了一项检测阴性的病例对照研究。我们于2026年2月4日从国家登革热监测数据库（SINAN-Dengue；强制通报）和圣保罗州卫生接种登记秘书（Rede Nacional de Dados em Saúde）中提取了研究期间人口统计学特征、合并症、登革热检测、登革热疫苗接种、住院和死亡的个人层面信息。病例定义为在症状出现后5天内通过NS1抗原或RT-PCR检测检测到的病毒学确诊登革热的急性发热性疾病发作。对照组为检测阴性的急性发热性疾病发作。监测数据与州疫苗接种登记处相关联。用混合效应logistic回归估计一次或两次TAK-003剂量后的疫苗有效性。研究结果：我们分析了166,390项测试：65,365项来自病例，101,025项来自对照组。一次剂量后疫苗对有症状登革热的有效性为59.2% (95% CI 56.1-62.0)，两次剂量后为73.1%（69.1-76.6）。在登革热住院治疗中，一次剂量后有效率为74.6%(62.7-82.7)，两次剂量后有效率为87.9%（73.0-94.6）。在1年的随访中，单剂量预防症状性疾病的效果没有减弱的迹象：270-364天的有效性为73.8%(64.7-80.6)，365天或更长时间的有效性为76.8%（59.3-86.8）。两剂保护保持稳定至1年（74.6%,95% CI 59.0-84.2, 270-365天）。结果在敏感性分析中是稳健的，并且在DENV-3循环增加时具有可比性。解释：我们的研究结果表明，TAK-003在大规模疫情期间对有症状的登革热和登革热住院治疗的青少年表现出持续1年的保护作用。值得注意的是，单次剂量显示出持续的有效性，没有证据表明在一年内会减弱，这产生了一个关于剂量减少的重要假设，值得继续进行长期观察评估。第二剂疫苗提供了最佳保护，特别是防止住院。这些发现加强了登革热疫苗接种作为一项公共卫生措施的重要性。资助：国家科学技术发展委员会。
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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