Genetic diversity of the Chikungunya virus E2 gene may have implications for the design of vaccines and therapeutic antibodies.

Chikungunya virus (CHIKV) is an arthropod-borne Alphavirus primarily transmitted by Aedes mosquitoes, causing sudden outbreaks with high morbidity and chronic polyarthritis. Following the US FDA approval of the first CHIKV vaccine in November 2023, concerns remain regarding vaccine efficacy due to the existence of at least three major CHIKV lineages. We conducted an in-silico genomic analysis of the CHIKV E2 glycoprotein to evaluate genetic diversity and evolutionary patterns relevant to vaccine and therapeutic antibody-binding effectiveness. The E2 gene exhibited substantial variation, reflecting high polymorphism and both intra- and inter-lineage differences. The variations detected may reduce antibody-antigen binding affinity, potentially compromising vaccine and therapeutic antibody efficacy. Our findings underscore the importance of incorporating pathogen genetic diversity into vaccine and therapeutic design. Long-term, pan-CHIKV vaccines could offer sustainable, cost-effective protection. Validation through in vitro and in vivo studies, alongside strengthened vector surveillance and control, is recommended to mitigate ongoing outbreaks.