Limited cross-protection induced by live attenuated ASF vaccines emphasizes caution for field use

African swine fever virus (ASFV) causes an often-fatal disease of domestic pigs and wild boars with a high socio-economic impact. The complexity of the large DNA genome and virion structure have hindered vaccine development. Gene-deleted modified live attenuated vaccines (LAVs) have proven to be the most successful and offer great potential to support control measures. However, their use introduces some safety risks, including transmission of the vaccine, potential genome mutations or recombination with field strains resulting in increased virulence. For successful vaccination, it is critically important to establish if the vaccine will protect against circulating strains to ensure efficacy and reduce opportunities to generate hybrid recombinants between the vaccine and field strains. In this commentary, we address the implications of recent studies demonstrating limited cross-protection offered by genotype II ASF LAVs against other circulating heterologous ASFV strains. These findings limit the safe and effective use of genotype II LAVs in these regions. We discuss priorities for future research to improve ASF LAVs and important considerations for their use in the field.