Perspectives on chikungunya vaccinology: from traditional platforms to epitope-driven rational design

Chikungunya virus (CHIKV) is an arthritogenic alphavirus transmitted mainly by female Aedes aegypti and Aedes albopictus mosquitoes. It causes significant morbidity and persistent arthralgia, with its global spread driven by Aedes vectors and viral lineage diversification. Vaccination remains the most cost-effective prevention strategy, but development is hindered by unpredictable outbreaks, undefined immune correlates of protection, and the variability of immunodominant epitopes. This review analyzes CHIKV's genomic and proteomic features, mechanisms of viral entry and transmission, immune evasion strategies, and host immune responses to inform vaccine design. It also critically assesses major vaccine platforms and their limitations. For example, the licensed vaccines Ixchiq (live-attenuated) and Vimkunya (virus-like particle) still facing limitations regarding safety in specific populations, durability of cross-protection, manufacturing complexity, and global accessibility. The review then highlights emerging epitope-based strategies informed by immunoinformatics, which have identified conserved viral epitopes to guide rational multi-epitope vaccine designs. These approaches may address limitations of conventional platforms by precisely targeting conserved protective epitopes, broadening human leukocyte antigen coverage, and reducing reactogenicity. While most epitope-based CHIKV vaccine candidates remain in computational or early preclinical stages, continued integration of immunoinformatics, structural vaccinology, and experimental validation could accelerate the development of safer and more broadly protective next-generation CHIKV vaccines.