Therapeutic approaches against dengue virus: current status of vaccines, antivirals, and monoclonal antibodies.

Abstract

Dengue virus (DENV) continues to pose a major global health challenge, with widespread distribution, frequent outbreaks, and four antigenically distinct serotypes complicating efforts for effective prevention and treatment. Despite decades of research, no universally protective vaccine or widely approved therapeutic exists, and the risk of antibody-dependent enhancement further complicates intervention strategies. This review provides an integrated perspective on dengue prevention and treatment, positioning vaccines, monoclonal antibodies, antiviral drugs, and host-directed therapies along the continuum of infection. It synthesizes recent advances in dengue prophylaxis and therapy, highlighting key innovations in vaccines, monoclonal antibodies, and antiviral compounds. Live-attenuated and chimeric tetravalent vaccines have progressed from early development to advanced clinical trials, demonstrating promising immunogenicity, safety, and potential for simplified dosing regimens. Concurrently, engineered monoclonal antibodies targeting conserved viral epitopes have improved neutralization breadth and reduced enhancement risk, while combination strategies may further limit viral escape. Antiviral development has explored both direct-acting and host-directed mechanisms, revealing potent candidates in preclinical models, although clinical translation remains challenging. Together, these advances illustrate a multifaceted approach to dengue control, integrating vaccine optimization, rational antibody design, and targeted therapeutics. By contextualizing recent progress and remaining challenges, this review underscores the urgent need for coordinated efforts to develop safe, effective, and broadly deployable interventions, ultimately supporting global efforts to reduce the burden of dengue.Trial registration: ClinicalTrials.gov identifier: NCT04722627, NCT05201794, NCT06006559, NCT05710224, NCT04273217.