Dengue Vaccines: Bridging Innovation and Public Health

Dengue is among the fastest-growing mosquito-borne viral infections worldwide and continues to pose a major public health challenge because no approved antiviral treatment is available. As a result, vaccination has become a cornerstone of dengue prevention. Several vaccine candidates have progressed through clinical development; however, questions remain regarding their efficacy, long-term safety, and ability to provide consistent protection against all four dengue virus serotypes. Over the last five years, findings from phase II and phase III clinical trials, post-licensure safety monitoring, and real-world effectiveness studies have substantially advanced the understanding of vaccine performance and influenced both regulatory recommendations and future vaccine development strategies. Despite these advances, important immunological issues remain unresolved, including the induction of balanced and durable immunity against all serotypes, identification of reliable correlates of protection, and clarification of how age and pre-existing dengue immunity affect vaccine responses. Clinical studies have reported variable outcomes, with several vaccines offering moderate protection against symptomatic dengue while showing differences in efficacy among serotypes and lower effectiveness in individuals without prior dengue exposure. Consequently, vaccination policies have evolved toward more targeted approaches, including pre-vaccination serological testing in selected settings, preferential use among seropositive populations, and integration of immunization programs with vector control and disease surveillance measures. Current research is focused on developing next-generation vaccines that provide stronger tetravalent immune responses, longer-lasting protection, and improved safety for seronegative individuals. In parallel, innovative clinical trial methodologies and detailed immunological analyses are being employed to better define the mechanisms underlying protective immunity. This review summarizes recent clinical evidence, emerging immunological knowledge, and evolving public health policies to provide an updated assessment of dengue vaccines and to identify key research priorities for achieving safe, effective, and equitable dengue prevention through vaccination. Keywords: Immunity; Dengue-vaccine; Tetravalent; Antibody-dependent enhancement; Serostatus-dependent efficacy; Vaccine-effectiveness; Pre-vaccination screening