Effectiveness of the TAK-003 dengue vaccine in adolescents during the 2024 outbreak in São Paulo, Brazil: a test-negative, case-control study.

BACKGROUND

Dengue is a substantial public health challenge in tropical regions, and is considered a global health threat owing to its expanding geographical range and increasing incidence as a result of climate change. Despite the availability of tetravalent dengue vaccines, real-world evidence on their effectiveness is scarce. We aimed to evaluate the vaccine effectiveness of the dengue vaccine TAK-003 in adolescents during the 2024 dengue outbreak in the state of São Paulo, Brazil.

METHODS

This test-negative, case-control study was conducted among adolescents aged 10-14 years in São Paulo state, Brazil, from Feb 20 to Dec 31, 2024. Cases were defined as individuals with acute febrile illness and virologically confirmed dengue, and controls as individuals with acute febrile illness who tested negative for dengue; in both groups, confirmation was based on NS1 antigen or RT-PCR testing within 5 days of symptom onset. Data were obtained from the national surveillance databases for dengue and the São Paulo State Secretary of Health vaccination registry. We used mixed-effects logistic regression models to estimate vaccine effectiveness against symptomatic, virologically confirmed dengue and against hospitalisation with dengue after one or two doses of the vaccine.

FINDINGS: Of 128 358 potentially eligible tests, 92 621 were included in the analysis: 43 873 from cases and 48 748 from controls. Adjusted vaccine effectiveness was 50·2% (95% CI 45·0-54·9) for the first dose and 61·7% (39·9-75·6) for the second dose against symptomatic dengue, and 67·5% (95% CI 43·4-81·3) for the first dose against hospitalisation with dengue. Protection against symptomatic disease began 14 days after the first dose (67·4% [57·2-75·1] at 14-27 days), but declined to 49·7% (30·4-63·6) after 90 days from the first dose. Sensitivity analyses showed the robustness of these findings, although estimates for the second dose were limited by the small number of events observed.

INTERPRETATION: TAK-003 was effective against symptomatic dengue and hospitalisation with dengue in adolescents during a large outbreak caused predominantly by dengue virus serotypes 1 and 2. These findings underscore the importance of real-world evidence in guiding dengue vaccination strategies, particularly in high-transmission settings and during emergency response use.

FUNDING: National Council for Scientific and Technological Development.

TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.