Self-Replicating RNA Viruses for Vaccine Development against Infectious Diseases and Cancer

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered for recombinant protein expression and vaccine development. Due to the presence of RNA-dependent RNA polymerase activity, subgenomic RNA can replicate close to 10⁶ copies per cell for translation in the cytoplasm providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. Self-replicating RNA viral vectors can be administered as replicon RNA at significantly lower doses than conventional mRNA, recombinant particles, or DNA plasmids. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus, etc., showing robust immune response and protection in animal models. Recently, paramyxovirus and rhabdovirus vector-based SARS-CoV-2 vaccines as well as RNA vaccines based on self-amplifying alphaviruses have been evaluated in clinical settings. Vaccines against various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been developed. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.