Therapeutic potential of bovine type III interferon (IFN-lambda3) as anti-bovine viral diarrhea virus agent

Authors: Dassanayake, Rohana; MENGHWAR, HARISH - Oak Ridge Institute For Science And Education (ORISE); Bickel, Kathryn; Holthausen, David; Diaz San Segundo, Fayna; RODRIGUEZ-CALZADA, MONICA - Oak Ridge Institute For Science And Education (ORISE); Medina, Gisselle; Attreed, Sarah; Falkenberg, Shollie; Kanipe, Carly; De Los Santos, Teresa; Casas, Eduardo

Submitted to: American Association of Immunologists Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 2/19/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Introduction: Recombinant bovine interferon lambda 3 (bovIFN-'3) 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-'3 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-'3 -SQ and BVDV (n= 6); group 6: Ad5-bovIFN-'3 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 humanely 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-'3 (groups 5 and 6) at necropsy. A greater protection of thymus-associated lymphoid follicles was observed in calves receiving Ad5-bovIFN-'3 SQ (group 5). Conclusion: These findings indicate that two doses of SQ administration of Ad5-bovIFN-'3 (~7 × 10e10 PFU/animal) can protect the thymus and prevent BVDV-induced thymic lymphoid follicle depletion. However, higher doses and multiple days of administration (Ad5-bovIFN-'3) may be required to fully prevent BVDV shedding and viremia.