The Potential of Disabled Infectious Single Cycle (DISC) Virus Platforms for Next Generation African Swine Fever Vaccine Development

African swine fever (ASF) is an emergency animal disease causing significant socio-economic impacts in affected areas on a global scale. While the first generation of ASF live-attenuated virus (LAV) vaccines to be recently approved for use in some countries offer potential to kerb the spread of ASF, non-live next-generation vaccines offer a safer alternative that can also be administered to animals in ASF-free zones. Among the next-generation vaccine platforms, disabled infectious single cycle (DISC) viruses are a promising replication-incompetent viral vaccine approach. In this review, we evaluate potential ASF virus gene targets that have been shown to have essential roles in the replication cycle and could be selected as deletion targets for producing DISC vaccines. We also summarise ASF virus genes for which there is evidence for a role in replication but have not yet been examined for their essential functions. Anticipated challenges for the development of an ASF DISC vaccine include limited cell substrates for development and manufacturing, genomic and phenotypic diversity of ASFV and potential for recombination events with co-infecting field viruses leading to reversion to virulence.