Administration Routes and Doses of the Attenuated African Swine Fever Virus Strain PSA-1NH Influence Cross-Protection of Pigs against Heterologous Challenge

African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF is endemic, potentially featuring multiple circulating ASFV isolates. The investigation of non-hemadsorbing naturally attenuated isolates and laboratory recombinant strains with a deletion in the EP402R gene has attracted interest. Our study aimed to assess the impacts of various administration routes and doses of the naturally attenuated ASFV-PSA-1NH (immunotype IV, genotype I) isolate on the manifestation of clinical signs of ASF and the level of protection against the heterologous ASFV-Stavropol 01/08 strain (seroimmunotype VIII, genotype II). The results demonstrated that the intranasal administration of a low dose of ASFV-PSA-1NH to pigs minimized the clinical signs of ASF and established a high level of protection against the heterologous strain ASFV-Stavropol 01/08. Despite the challenges in standardizing the dosage for intranasal administration, this approach appears as a viable alternative in ASF vaccination.