The need for balanced dengue vaccine protection: Insights from Thai surveillance data on four serotypes.

Dengue virus (DENV), comprising four distinct serotypes (DENV-1 to DENV-4), poses a major public health challenge in tropical regions. Infection with one serotype confers long-term immunity to that serotype alone, while subsequent heterologous infections are associated with increased risk of severe disease, necessitating vaccines that induce durable, balanced immunity across all serotypes. However, achieving such balance immunity remains a central challenge for dengue vaccine development. Using passive surveillance data from Kamphaeng Phet, Thailand (2004-2022), we characterized long-term serotype circulation and contributions to clinical dengue burden in a hyperendemic setting. We observed sustained co-circulation of all four serotypes over nearly two decades, with periodic shifts in dominant serotype. Among 6,840 PCR-confirmed dengue cases, the majority of which were hospitalized, DENV-1 through DENV-4 accounted for 32.8%, 25.9%, 24.8%, and 16.5% of detected dengue cases, respectively. Compared with DENV-1, clinically-apparent DENV-2 and DENV-4 infections were more likely to represent secondary infections (odds ratio 4.94 and 5.24, respectively) and occurred at older ages, underscoring the context-dependent clinical expression of different serotypes. Together, these findings demonstrate that all four dengue serotypes contribute meaningfully to clinical disease burden in Thailand and caution against de-emphasizing individual serotypes based on transient epidemiologic patterns. These results reinforce the importance of tetravalent vaccine strategies alongside continued evaluation of vaccine performance in evolving epidemiologic settings.