A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces sterile immunity against classical swine fever

► We developed and evaluated a novel gene-based vaccine against classical swine fever (CSF). ► The vaccine is based on adenovirus/alphavirus replicon chimeric vector. ► The vaccine induced stronger immune responses than conventional vector-based vaccines. ► Pigs immunized with the vaccine were completely protected from lethal challenge. ► It represents the first gene-based vaccine against CSF that is able to confer sterile immunity.