Exploring approaches and advancements in the development and evaluation of multi-epitope subunit vaccines against tick-borne viruses

Tick-borne viruses (TBVs) pose significant public health challenges worldwide, causing severe diseases such as hemorrhagic fevers and encephalitis. Given the limitations of existing therapeutic and preventive measures, the development of effective vaccines represents a critical strategy for controlling TBV-related infections. This review explores recent advancements in the design and evaluation of multi-epitope subunit vaccines targeting key TBVs, including hemorrhagic fever viruses (e.g., Crimean-Congo hemorrhagic fever virus, Severe fever with thrombocytopenia syndrome virus), encephalitis viruses (e.g., West Nile virus, Tick-Borne Encephalitis virus), and emerging or less common TBVs (e.g., Banna virus, Yezo virus). Emphasis is placed on the application of immunoinformatics and reverse vaccinology for the identification of epitopes capable of inducing robust humoral and cellular immune responses. We summarize epitope prediction methodologies, vaccine construct designs, immune simulation results, and molecular docking findings. While current studies demonstrate strong in silico potential, we underline the urgent need for experimental validation to support the clinical development of these vaccine candidates.