Efficacy, Immunogenicity, Safety, and Evidence Independence of CYD-TDV and TAK-003 Dengue Vaccines in Children and Adolescents: A Systematic Review and Meta-Analysis

Background/Objectives: The efficacy and safety profiles of CYD-TDV and TAK-003 are established, but multiple publications may derive from the same randomized trial population and therefore not represent independent evidence. We evaluated efficacy, immunogenicity, and safety while distinguishing independent trials from overlapping follow-up reports and interpreting absolute effects within each programme. Methods: We conducted a PRISMA 2020 systematic review and meta-analysis of randomized trials and follow-up reports from five databases. Outcomes included virologically confirmed dengue, hospitalization, severe dengue, serotype-specific efficacy, immunogenicity, and safety. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated; immunogenicity and safety were synthesized narratively. RoB 2 and GRADE were applied. Results: Nine reports were included. CYD-TDV reduced virologically confirmed dengue (RR = 0.41; 95% CI: 0.35–0.48) and hospitalization (RR = 0.41; 95% CI: 0.25–0.67). Across two independent CYD-TDV trials, absolute reductions were 23.2 virologically confirmed dengue cases per 1000 participants (NNV = 44) and 12.0–50.0 hospitalizations per 1000 (NNVs = 84–20). In the primary TIDES report, TAK-003 reduced virologically confirmed dengue (RR = 0.28; 95% CI: 0.22–0.35) and hospitalization (RR = 0.10; 95% CI: 0.05–0.18), with absolute reductions of 23.6 and 12.9 per 1000 (NNVs = 43 and 78). Later TIDES reports extended follow-up of the same population. Conclusions: Both vaccines reduced dengue outcomes within their respective trial programmes. Absolute effects should be interpreted according to baseline risk and trial context, not as direct between-vaccine comparisons. The synthesis distinguishes extended follow-up from independent replication.