(824) Therapeutic potential of bovine type III interferon (IFN-λ3) as anti-bovine viral diarrhea virus agent

Introduction/Rationale: Recombinant bovine interferon lambda 3 (bovIFN-λ3) can effectively clear bovine viral diarrhea virus (BVDV) in cell cultures. Based on this finding, we evaluated whether a replication-defective human adenovirus type 5 (Ad5) vector expressing bovIFN-λ3 can reduce the severity of BVDV infection and protect against thymus-associated lymphoid follicle depletion in calves.

Methods: Twenty-four colostrum-deprived calves were divided into six groups as follows: group 1: uninoculated control (n= 3); group 2: BVDV challenged control (n= 3); group 3: Ad5-blue (empty vector) subcutaneous [SQ] and BVDV (n=3); group 4: Ad5-blue intranasal [IN] and BVDV (n= 3); group 5: Ad5-bovIFN-λ3 -SQ and BVDV (n= 6); group 6: Ad5-bovIFN-λ3 IN and BVDV (n= 6). Calves in groups 3-6 received the respective Ad5 vectors (~7 × 10e10 plaque forming units (PFU) per animal) either IN or SQ one day before and one day after BVDV IN challenge (~6 × 10e7 TCID50 per animal). Nasal swabs and blood samples were collected throughout the study, and calves were euthanized 14 days after BVDV challenge.

Results: Calves inoculated with BVDV experienced a transient decline in lymphocytes and monocytes during the study period. Real-time PCR analysis showed no significant changes in BVDV shedding or viremia amongst the groups. A lack of BVDV-induced thymic weight reduction was observed in calves treated with Ad5-bovIFN-λ3 (groups 5 and 6) at necropsy. A greater protection of thymus-associated lymphoid follicles was observed in calves receiving Ad5-bovIFN-λ3 SQ (group 5).

Conclusion: These findings indicate that two doses of SQ administration of Ad5-bovIFN-λ3 (~7 × 10e10 PFU/animal) can protect the thymus and prevent BVDV-induced thymic lymphoid depletion. However, higher doses or multiple days of administration (Ad5-bovIFN-λ3) may be required to fully prevent BVDV shedding and viremia.