Boosting self-amplifying RNA vaccine efficacy

The groundbreaking success of mRNA-based vaccines in combating COVID-19 has driven intense interest in RNA technologies and their optimisation.

Self-amplifying mRNA (saRNA) technology represents a powerful next-generation vaccine platform. saRNA are derived from alphavirus replicons that are engineered to encode both the antigen of interest and viral replication machinery.

This allows saRNA to self-replicate within host cells, leading to prolonged antigen expression at lower doses compared to conventional mRNA vaccines. Therefore, saRNA holds great promise as a novel strategy for efficient vaccine design and its ability to amplify antigen production within cells offers potential applications in gene therapy, cancer immunotherapy, and protein replacement therapies.

The cis-expression of Nodamuravirus (NoV) B2 protein, a well-known viral suppressor of RNAi, from Chikungunya virus (CHIKV) or Venezuela equine encephalitis (VEEV) genome-based saRNAs was shown to increase their ability to express a gene of interest in both embryonic stem cells and somatic cells, whilst preserving saRNA’s self-adjuvant properties.

This presents a novel strategy to enhance saRNA vaccine efficiency by co-expressing NoV B2 protein, which boosts transgene expression while preserving self-adjuvanticity.

By increasing saRNA stability and function without disrupting the interferon response, this approach holds significant promise for next-generation RNA vaccines and therapeutic applications.