Self‐Replicating RNA Viruses for Vaccine Development

Self-replicating RNA viruses including alphaviruses, flaviviruses, measles viruses, and rhabdoviruses have been engineered for vaccine development against infectious diseases and cancers. The self-replication of RNA in host cell cytoplasm substantially increases therapeutic efficacy and allows the administration of reduced doses of vector required for achieving efficient immune responses. The use of recombinant particles, RNA replicons, or plasmid-based DNA replicons has broadened the potential of the delivery of self-replicating RNA virus vectors. Robust immune responses and protection against challenges with lethal pathogens have been demonstrated in rodents and primates. Similarly, immune responses, inhibition of tumor growth, tumor eradication, and protection against tumor challenges have been achieved in various animal tumor models. Clinical trials have also been conducted with self-replicating RNA viruses for infectious diseases and cancers, showing good safety, tolerability, and immune responses. The Ervebo vaccine, based on vesicular stomatitis virus vectors, has been approved for vaccination against Ebola virus disease.