TAK-003 Dengue Vaccine Safety: Evidence from a Systematic Review and Meta-analysis of Clinical Trials

Abstract

Dengue remains a growing global health threat with no specific antiviral treatment available. TAK-003, a tetravalent live-attenuated vaccine, offers a promising preventive option, particularly for seronegative individuals, necessitating a comprehensive safety evaluation to inform public health strategies.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analysis by searching various indexes and registries up to May 31, 2025. Phase 1–3 RCTs comparing TAK-003 with placebo or control vaccines were included. Pooled risk ratios (RRs or odds ratios (ORs with 95% confidence intervals (CIs were calculated; heterogeneity and subgroup analyses were performed. Eighteen clinical trials were included in the systematic review, and 11 clinical trials were included in the meta-analysis. No significant difference emerged in serious adverse events (SAEs (RR: 0.91, 95% CI: 0.55–1.50 or mortality (RR: 0.38, 95% CI: 0.04–3.92 between TAK-003 and placebo. Local solicited adverse events—especially injection-site pain and redness—were significantly higher with TAK-003 after the first dose (OR: 5.24, 95% CI: 1.02– 27.02. Systemic adverse events like headache and myalgia were also slightly higher in the TAK-003 group after the first dose (OR: 1.48, 95% CI: 1.10–1.99 but not after the second. Unsolicited adverse events and pregnancy outcomes were comparable, revealing no new safety concerns. TAK-003 shows an acceptable safety profile, with no rise in SAEs or mortality. Although local and mild systemic reactions were more common, they were brief and tolerable, supporting an acceptable safety profile within the available randomized clinical trial evidence.