Genomic and Immunological Insights Into Chikungunya Virus Evolution During the 2018 and 2023-24 Outbreaks in Southern India.

Chikungunya virus (CHIKV) continues to pose a significant public health threat due to recurrent outbreaks driven by antigenic drift, vector adaptation and potential changes in virulence. This study examined the genetic and antigenic characteristics of CHIKV isolates from the 2018 and 2023-24 outbreaks in southern India. Whole-genome sequencing and phylogenetic analysis were performed on outbreak isolates. Structural protein B-cell epitopes were analyzed and mutations associated with vector adaptation and neurovirulence were screened. Serum samples collected in mid-2023 were tested using plaque reduction neutralization test against both outbreak strains. All isolates clustered within the C2.3 clade of the ECSA-IOL genotype and showed close relationship with strains from India, Kenya, Thailand, and Bangladesh. A total of 71 nonstructural and 45 structural mutations were identified relative to the reference strain (S27), with fewer variations in the 2023-24 isolates when compared with 2018 isolates. Adaptive mutations E1:K211E, E2:V264A, and E2:I211T indicated possible dual-vector adaptation. No established neurovirulence mutations were detected. Neutralization and epitope analyzes showed reduced antibody efficacy against 2023-24 isolates. The 2023-24 CHIKV strains remain genetically stable but exhibit adaptive mutations that may enhance transmission and reduce neutralization, highlighting the need for continued genomic and immunological surveillance.