Novel BVDV-2 mutants as new candidates for modified-live vaccines

Protection against Bovine viral diarrhea virus (BVDV) type 2 infection of commercially available vaccines is often limited due to marked genetic and antigenic differences between BVDV types 1 (BVDV-1) and 2 (BVDV-2). Therefore, the immunogenicity of selected BVDV-1 and BVDV-2 mutants derived from infectious full-length cDNA clones and their use as modified-live vaccine candidates against challenge infection with a virulent heterologous BVDV-2 field isolate were investigated. Deletion mutants of BVDV-1 and BVDV-2 lacking a part of the Npro gene (BVDV-1?Npro/BVDV-2?Npro) were used as well as a packaged replicon with a deletion in the structural core protein encoding region (BVDV-2?C-pseudovirions). The 25 calves used in this vaccination/challenge trial were allocated in five groups (n = 5/group). One group received BVDV-1?Npro (1 shot), one group BVDV-2?Npro (1 shot), one group received both, BVDV-1?Npro and BVDV-2?Npro (1 shot), and one group was immunised with the BVDV-2?C-pseudovirions (2 shots). The fifth group served as non-vaccinated control group. All groups were challenged intranasally with the BVDV-2 strain HI916 and monitored for signs of clinical disease, virus shedding and viremia. All tested BVDV vaccine candidates markedly reduced the outcome of the heterologous virulent BVDV-2 challenge infection showing graduated protective effects. The BVDV-2?Npro mutant was able to induce complete protection and a "sterile immunity" upon challenge. Thus it represents a promising candidate for an efficacious future live vaccine.