Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer

Replicon RNA (RepRNA) represents a cutting-edge technology in the field of vaccinology, fundamentally transforming vaccine design and development. This innovative approach facilitates the induction of robust immune responses against a range of infectious diseases and cancers. RepRNA vaccines leverage the inherent capabilities of RNA-dependent RNA polymerase associated with self-replicating repRNA, allowing for extreme replication within host cells. This process enhances antigen production and subsequently stimulates adaptive immunity. Additionally, the generation of double-stranded RNA during RNA replication can activate innate immune responses. Numerous studies have demonstrated that repRNA vaccines elicit potent humoral and cellular immune responses that are broader and more durable than those generated by conventional mRNA vaccines. These significant immune responses have been shown to provide protection in various models for infectious diseases and cancers. This article will explore the design and delivery of RepRNA vaccines, the mechanisms of immune activation, preclinical studies addressing infectious diseases and tumors, and related clinical trials that focus on safety and immunogenicity.