LAUSR

Flaviviruses are major human pathogens that continue to pose a global health threat, and vaccination is an effective strategy to protect against disease from several flaviviruses. Flavivirus vaccines are believed to confer protection primarily through antibody responses; however, the role of T cells in vaccine immunity remains less explored despite demonstrated contribution in the response to natural infection. This review examines T cell responses induced by licensed or developing flavivirus vaccines, their contribution to protection, and key findings highlighting the importance of cellular immunity. We discuss the role of memory T cells, including CD4+ and CD8+ subsets, in flavivirus vaccine‐induced immunity and compare the immunogenicity of live attenuated versus inactivated vaccines. We also discuss the significance of T cell immunity, cross‐reactivity, and vaccine platform design in shaping durable and broad protection. Additionally, we broaden the discussion toward other human RNA viruses, including the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). A better understanding of the role of T cell immunity will be essential for optimizing the use of current flavivirus vaccines and developing next‐generation approaches capable of providing long‐lasting immunity against emerging and re‐emerging flavivirus threats.