Chunhao Jiang, Ruojia Huang, Rui Luo, Tao Wang, Hua‐Ji Qiu, Yuanhao Sun
African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating swine disease. To date, no commercial ASF vaccine has been authorized for global marketing except in Vietnam, and emerging genotype I/II recombinant ASFV strains pose severe new challenges to ASF control. Live-attenuated vaccines (LAVs) are widely recognized as the most promising strategy for ASF control. This review systematically summarizes three conventional development strategies for ASF LAVs, dissects the molecular mechanisms of two core bottlenecks-intergenotypic ASFV recombination and vaccine strain reversion to virulence-and elaborates rational design strategies for next-generation LAVs based on cutting-edge technologies. These strategies can fundamentally mitigate the aforementioned risks, offering promising solutions for addressing the major limitations of conventional ASF LAVs.