Dengue virus (DENV) disease severity is strongly influenced by prior flavivirus exposure, with sequential infections shaping immune outcomes through cross-reactive and often non-neutralizing responses that can promote severe disease. In DENV-immune individuals, their immune repertoire is linked to immune protection versus pathology and reflects a cumulative exposure history, shaped not only by specificity but also factors such as T cell polarization and antibody subclass distribution. Beyond the influence of prior dengue, other flaviviruses such as Japanese encephalitis virus (JEV) can modify subsequent DENV responses and may increase the risk of symptomatic or severe disease. For example, individuals with waning vaccine-induced immunity to JEV experience more warning signs of severe dengue in a largely DENV-naive population. These observations emphasize the importance of considering immune imprinting across multiple flaviviruses when evaluating disease risk and raise the possibility of strategic use of vaccine campaigns to shape immune outcomes to lower risk. In this presentation, I will discuss how sequential flavivirus exposures shape adaptive immunity and consider the implications for vaccine design in populations with diverse flaviviral immune histories.