Therapeutic potential of bovine type III interferon (IFN-γ3) as anti-bovine viral diarrhea virus agent 2305378

Abstract

Abstract Introduction Recombinant bovine interferon lambda 3 (bovIFN-γ3) 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-γ3 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-γ3 -SQ and BVDV (n = 6); group 6: Ad5-bovIFN-γ3 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-γ3 (groups 5 and 6) at necropsy. A greater protection of thymus-associated lymphoid follicles was observed in calves receiving Ad5-bovIFN-γ3 SQ (group 5). Conclusion These findings indicate that two doses of SQ administration of Ad5-bovIFN-γ3 (∼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-γ3) may be required to fully prevent BVDV shedding and viremia. Funding Source USDA CRIS 5030-32000-229-000-D Topic Categories Vaccines and Immunotherapy (VAC)