Dengue Vaccines in a Changing Epidemiological Landscape: Current Evidence, Unresolved Challenges, and Public Health Considerations

This narrative review synthesizes current evidence on dengue vaccines, highlighting the strengths and limitations of CYD-TDV, TAK-003, and Butantan-DV, and underscores the need for integrated, risk-stratified vaccination strategies in a changing epidemiological landscape.

Susanna Esposito; N. Principi· Vaccines· 2026· DOI 10.3390/vaccines14090729

The core problem

Dengue has expanded rapidly beyond traditional tropical and subtropical regions, driven by climate change, urbanization, population mobility, and the spread of competent *Aedes* vectors. Vaccination is an increasingly important component of dengue prevention, but development has been complicated by four viral serotypes, antibody-dependent enhancement (ADE), variable baseline serostatus, and the need for balanced and durable tetravalent immunity. The authors conducted a narrative review to critically evaluate the current evidence on dengue vaccines, including licensed products and advanced candidates, and to discuss public health considerations for their implementation.

The authors conducted a narrative review of PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, and relevant public health and regulatory sources. Evidence on dengue epidemiology, immunopathogenesis, licensed vaccines, advanced candidates, efficacy, immunogenicity, safety, durability, and implementation was critically evaluated. Priority was given to randomized trials, long-term follow-up studies, regulatory assessments, and surveillance data. Evidence was synthesized descriptively without formal meta-analysis or risk-of-bias assessment.

Introduction

Dengue has expanded rapidly beyond traditional tropical and subtropical regions, driven by climate change, urbanization, population mobility, and the spread of competent *Aedes* vectors. Vaccination is an increasingly important component of dengue prevention, but development has been complicated by four viral serotypes, antibody-dependent enhancement (ADE), variable baseline serostatus, and the need for balanced and durable tetravalent immunity. The authors conducted a narrative review to critically evaluate the current evidence on dengue vaccines, including licensed products and advanced candidates, and to discuss public health considerations for their implementation.

The review highlights that dengue vaccination should be integrated with surveillance, vector control, clinical preparedness, and risk communication. Population-based vaccination is most appropriate in high-transmission settings, whereas selective, risk-based strategies are preferable in temperate regions. Continued pharmacovigilance and effectiveness monitoring are essential to guide safe and equitable implementation. The authors emphasize that the complexity of dengue immunology and epidemiology necessitates tailored vaccination approaches and ongoing research to address unresolved challenges, including the need for a vaccine that provides balanced protection across all four serotypes regardless of baseline serostatus.

Praktisi kesehatan, peneliti klinis, dan pembaca Research Digest.

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