Chikungunya virus fidelity-variant live-attenuated vaccine

The attenuation of the CHIKV LAV strain 181 clone 25 (CHIKV-181/25) relies on two point mutations in the E2 surface glycoprotein responsible for host cell binding and entry, making it particularly prone to phenotypic reversion, a common concern for replication-competent vaccines. Inherently high error rates associated with RNA virus replication have posed a challenge for rational LAV development where stable incorporation of attenuating elements is necessary for establishing safety in pre-clinical models. In this study, we incorporate two replicase mutations into CHIKV-181/25 previously demonstrated to modulate CHIKV replication fidelity along with additional attenuating features that cannot be eliminated from the LAV by point mutation.