Dengue Vaccines, Antiviral Therapeutics and Emerging Diagnostic Biomarkers: Advances, Constraints and Translational Priorities

Abstract

Dengue control is entering a period in which vaccination, direct-acting antiviral development and increasingly sophisticated diagnostics can no longer be evaluated as separate technical domains. Vaccine performance is shaped by baseline dengue serostatus, circulating serotype and duration of follow-up; antiviral efficacy depends on treatment early in a brief viraemic phase; and diagnostic or prognostic biomarkers must function across changing immune backgrounds created by prior infection and vaccination. This critical narrative review integrates evidence on dengue vaccines, therapeutic development and emerging biomarkers, with emphasis on clinical translation rather than platform novelty alone. Literature published from 1 January 2009 to 19 July 2026 was considered, alongside earlier seminal work where necessary, using major biomedical and multidisciplinary scholarly sources, regional Latin American indexes and authoritative public-health documents. The strongest vaccine evidence supports meaningful protection against virologically confirmed and hospitalised dengue, but also demonstrates that apparent aggregate efficacy can conceal serotype- and serostatus-specific uncertainty. The legacy of CYD-TDV established the importance of baseline immunity for benefit-risk assessment; TAK-003 has accumulated long-term randomised and real-world evidence, while residual uncertainty in dengue-naive recipients against some serotypes remains relevant to programme design; and single-dose Butantan-DV has produced encouraging five-year efficacy data against circulating DENV-1 and DENV-2, although absence of field efficacy data for DENV-3 and DENV-4 and a 2026 precautionary programme interruption in Brazil require careful interpretation. Therapeutic research has moved beyond largely negative repurposing trials towards potent replication-complex inhibitors, with mosnodenvir providing clinical proof of antiviral activity in a controlled human infection model, but efficacy for treatment of naturally acquired dengue remains unestablished. Diagnostic evidence confirms the time-dependent complementarity of RT-PCR, NS1 antigen and serology, while transcriptomic, metabolomic, mast-cell, endothelial and cytokine markers show promise for early severity stratification without yet meeting the evidentiary standard for routine triage. The principal translational priority is therefore integration: diagnostics that identify infection and risk early enough to guide antiviral use, vaccine strategies calibrated to serotype and immune context, and prospective biomarker validation against clinically actionable decisions.