Genetic polymorphisms in the E2 glycoprotein of chikungunya virus (2014-2023) and their potential implications for immunity and vaccine design.

BACKGROUND

Genetic polymorphisms that have accumulated in Chikungunya virus (CHIKV) strains circulating in Brazil remain poorly characterized, limiting our understanding of their implications for vaccine design, epidemiological profiling, and preparedness for future outbreaks.

METHODS

In this study, we investigated genetic polymorphisms in CHIKV circulating in Brazil and worldwide from 2014 to 2023, and assessed their potential relevance to vaccine development and epidemic preparedness. We analyzed the conservation of experimentally validated epitopes targeted by neutralizing antibodies across CHIKV E2 envelope glycoprotein sequences. In addition, amino acid substitutions of potential biological significance were identified and mapped onto a 3D model of the viral envelope protein.

FINDINGS: As main results, we found that the known epitopes are poorly conserved in Brazilian CHIKV isolates, as well as across global genotypes. In addition, a substantial number of polymorphisms were identified at protein sites involved in critical biological processes, such as recognition by neutralizing antibodies and binding to cellular receptors, mainly located in domains A and B of the CHIKV E2 envelope glycoprotein.

CONCLUSIONS

These findings indicate that a relevant number of mutations have accumulated in CHIKV circulating in Brazil and worldwide, with potential to impact immunological control of the virus and its replication and pathogenesis.