Comparative Efficacy of CYD-TDV, TAK-003, and Butantan-DV Dengue Vaccines in the Pediatric Population: A Network Meta-Analysis

Abstract

Introduction: Dengue virus is a major global health threat with no specific antiviral therapy available. Vaccines such as CYD-TDV, TAK-003, and Butantan-DV exist but differ significantly in backbone designs, serological status requirements, and efficacy, creating inconsistency in the medical literature. This study aims to evaluate and indirectly compare the overall efficacy of CYD-TDV, TAK-003, and Butantan-DV vaccines in preventing dengue in the pediatric population using a network meta-analysis.

Method: A systematic review and network meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five electronic databases were searched up to March 2026 for randomized controlled trials assessing CYD-TDV, TAK-003, or Butantan-DV against a placebo in populations under twenty years old. The primary outcome was vaccine efficacy against virologically confirmed dengue, analyzed using random-effects pairwise and Bayesian network meta-analysis.

Results: Thirty-two studies from eleven randomized controlled trial reports were included. Against a placebo, CYD-TDV (risk ratio 0.780), TAK-003 (risk ratio 0.406), and Butantan-DV (risk ratio 0.291) significantly reduced dengue infection risk. Butantan-DV and TAK-003 demonstrated superior overall protection profiles compared to CYD-TDV. Specifically, Butantan-DV was most effective against dengue virus serotype 1, while TAK-003 was dominant against serotype 2. In seronegative individuals, Butantan-DV and TAK-003 provided effective protection without the severe safety risks associated with CYD-TDV.

Conclusions: The single-dose Butantan-DV offers the highest overall efficacy and safety profile, particularly for seronegative populations. TAK-003 serves as a highly accessible alternative with clinical benefits across varying serological statuses, whereas the utility of CYD-TDV is severely compromised by safety risks in seronegative children.

Keywords: Dengue virus, vaccines, network meta-analysis, pediatric, efficacy.