Transcriptomic analysis among sub-clinically ill cattle following Bovine Respiratory Disease vaccine protocol and challenge with Bovine Viral Diarrhea Virus

Background: Bovine viral diarrhea (BVD) is a widespread immunosuppressive disease of cattle. Infection with bovine viral diarrhea virus (BVDV) can also be sub-clinical and persistent in herds, leading to high economic impact to cattle producers. Complicating this is BVD’s ability to predispose cattle to bovine respiratory disease (BRD) complex. Although many producers vaccinate for BRD to help protect herds from this predisposition, there are gaps in the knowledge of differences between the protection afforded by modified live (MLV) or killed (KV) vaccines, and the level of cross-protection they offer to BVDV. These knowledge gaps affect the economic impact of BVDV because, with more information on vaccine efficacy, cattle producers could possibly reduce treatment costs and disease spread. The study objective was to determine the level of BRD vaccine cross-protection by examining the underlying differential gene expression response to a sub-clinical BVDV challenge in Nellore-Angus cattle. Results: Statistical analysis of clinical data showed that MLV had lower BVDVa, BVDV2, and BVDVb antibody titers (p < 0.001) compared to the KV vaccine. The three treatment groups (no vaccine (NON), KV, MLV; n = 5 per group) were also compared by RNA-seq analysis of buffy coats from cattle at 14 dpi. The BRD KV group displayed a higher antibody (AB) response, however transcriptomic analysis showed that the KV group still showed high innate gene expression at 14 dpi. The MLV showed displayed a higher number of adaptive and cell-mediated immune response genes being differentially expressed in reaction to challenge at 14 dpi. Analysis also showed the difference in vaccine cross-protection involved evidence of complement activation as part of the MLV bolstered immune response. Lack of detection of complement activation in the KV group could explain the higher titers, while complement activation in the MLV group could lead to less AB response due to better cell-mediated response. Upregulation of MHC molecules and T-cell related gene expression was also observed within the MLV group only. Conclusions: Although both vaccines provide some level of cross-protection over non-vaccinated animals, the results point to MLV producing cross-protection that extends the adaptive immune response to BVDV.