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.

Abstract

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. 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. 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. 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. No dedicated funding.