African swine fever (ASF) is a highly pathogenic, lethal, and contagious viral disease caused by African swine fever virus (ASFV). ASF can infect domestic pigs and wild boars of any breed and age and cause high fever, bleeding of the reticuloendothelial system, and even death. ASFV, the pathogenic agent of ASF, is the only member of the Asfarviridae family and the Asfivirus genus. The ASFV CD2V protein, which is encoded by the EP402R gene, is a glycosylated protein that plays an important role in viral pathogenesis, orientation of the host, and immune escape. CD2V protein is an important protective antigen of ASFV, which provides ASF with serotype-specific cross-protective immunity. Immune pigs with ASFV CD2V protein can produce HAI and antibodies against M-II, which can be partly protected during challenge with homologous virus strains.