Towards Safe African Swine Fever Vaccines: The A137R Gene as a Tool to Reduce Virulence and a Promising Serological DIVA Marker Candidate

African swine fever (ASF) is an emerging disease caused by the African swine fever virus (ASFV), which is a great threat to the swine industry worldwide. Currently registered vaccines that have demonstrated protection against the homologous ASFV strains are live attenuated vaccines based on recombinant ASFV strains with the deletions of virulence-associated genes. In this study, we evaluated the deletion of the <i>A137R</i> gene in the ASFV virulent Stavropol_01/08 strain isolated in Russia in 2008. Our animal experiment results demonstrated that the deletion of the <i>A137R</i> gene did not lead to the full attenuation of this strain, and increasing the dose of the <i>A137R</i>-deletion mutant during infection led to the death of 87.5% of the infected animals. In this report, we also demonstrated that immunofluorescence (IFA) and Western blotting assays based on the recombinant p11.5 protein can be used to detect antibodies in animals infected with the attenuated ASFV variants of several genotypes/serotypes. Both assays were specific to ASFV p11.5 protein and showed negative results when examining the sera of the non-infected animals or those infected with the <i>A137R</i>-deletion mutant. Therefore, we propose to use the p11.5 protein along with other previously proposed ASFV proteins, such as CD2v, as negative antigenic DIVA markers for an attenuated ASF vaccine.