Advances in African swine fever vaccine development: challenges and prospects

IMPORTANCE: African swine fever (ASF) is a devastating transboundary disease of domestic pigs and wild boar, causing severe economic losses with mortality approaching 100% in acute infections. Despite decades of research, there is no widely available, internationally licensed ASF vaccine, and control remains dependent on biosecurity, culling, and movement restrictions. The complex biology of African swine fever virus (ASFV), immune evasion, and incomplete understanding of protective immunity continue to impede vaccine development. OBSERVATIONS: Vaccine development includes live attenuated vaccines (LAVs), subunit vaccines, DNA vaccines, viral vectors, and newer approaches such as virus-like particles (VLPs) and mRNA platforms. LAVs remain the most promising in controlled studies (e.g., BA71ΔCD2) and include candidates with limited emergency authorizations in some settings (e.g., HLJ/18-7GD), but safety concerns (reversion risk), environmental persistence, and DIVA limitations remain major barriers. Subunit and nucleic acid vaccines offer improved safety but have shown limited protection in challenge studies. Advances in structural biology, genomics, and immunology are accelerating rational design, with VLPs emerging as a promising next-generation approach to balance safety and immunogenicity. CONCLUSIONS AND RELEVANCE: Recent progress in ASFV structural understanding, immune correlates of protection, and vaccine engineering supports cautious optimism. Success will likely require standardized evaluation, robust DIVA strategies, and coordinated international development and deployment pathways.