Transcriptional profiles of vaccine-induced protection in bovine herpesvirus-1 and mycoplasma bovis-challenged bison

Authors: Zakrzewicz, Anna; Kaplan, Bryan; MENGHWAR, HARISH - Oak Ridge Institute For Science And Education (ORISE); Kanipe, Carly; Boggiatto, Paola; CRAWFORD, LAUREN - Oak Ridge Institute For Science And Education (ORISE); Olsen, Steven; Briggs, Robert; Tatum, Fred; Dassanayake, Rohana; Casas, Eduardo

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2025
Publication Date: 9/16/2025
Citation: Goldkamp, A.K., Kaplan, B.S., Menghwar, H., Kanipe, C.R., Boggiatto, P.M., Crawford, L.S., Olsen, S.C., Briggs, R.E., Tatum, F.M., Dassanayake, R.P., Casas, E. 2025. Transcriptional profiles of vaccine-induced protection in bovine herpesvirus-1 and mycoplasma bovis-challenged bison. Frontiers in Veterinary Science. 12. Article 1667623. https://doi.org/10.3389/fvets.2025.1667623.
DOI: https://doi.org/10.3389/fvets.2025.1667623

Interpretive Summary: Mycoplasma bovis (M. bovis) is a pathogen associated with respiratory disease in cattle. In bison, M. bovis is associated with increased mortality rates and clinical symptoms of respiratory disease. The objective of this study was to identify if there are differences in gene expression in tissues or in blood when an animal is vaccinated with M. bovis antigens compared to control. Blood collected 36 days after vaccination and 6 days after viral infection displayed the greatest differences in gene expression. In tissues, vaccination had the greatest impact on gene expression in spleen. The differentially expressed genes identified in this study could potentially be used for intervention strategies.

Technical Abstract: Mycoplasma bovis is a significant pathogen in American bison (Bison bison), causing chronic respiratory disease with high mortality rates. A recent study demonstrated that a recombinant protein subunit vaccine containing M. bovis elongation factor thermal unstable (EFTu) and heat shock protein 70 (Hsp70) antigens induced immunity in bison, leading to reduced lung lesions and bacterial loads following experimental M. bovis challenge. The objective of this study was to investigate transcriptional responses underlying vaccine-induced protection in vaccinated (n = 5) compared to unvaccinated control (n = 4) bison following M. bovis infection. Two doses of vaccines were administered subcutaneously with the first occurring at day 0 and the second at 21 days post-vaccination (DPV), respectively. This was followed by intranasal inoculation with bovine herpesvirus-1 (BHV-1) at 36 DPV and M. bovis at 40 DPV. RNA sequencing was performed on liver, palatine tonsil (PT), retropharyngeal lymph node (RPLN), tracheobronchial lymph node (TBLN), spleen, and whole blood samples. Whole blood samples were collected at several time points (1st vaccination (Day 0), 2nd vaccination (21 days post-vaccination), BHV-1 inoculation (36 DPV), M. bovis inoculation (40 DPV), and 1 week post M. bovis inoculation (47 DPV). The greatest number of differentially expressed transcripts (DETs) were found in blood samples collected at 36 DPV (123 total DETs) and in spleen (57 DETs). At 36 DPV, DETs upregulated in vaccinated animals were significantly enriched in cell adhesion, T-helper cell (Th1/Th2/Th17) differentiation, and antigen processing and presentation. This signifies a robust response to the 2nd vaccine dose, which caused increased expression of CD3E, CD4, and CD8B correlating to heighted T cell proliferation. Notably, transcription factors TBX21 and GATA3 were upregulated in vaccinated animals, suggesting enhanced protection through T helper cell differentiation. Spleen-specific regulation included genes involved in innate immune response, such as LGALS3 and GBP-1. These findings highlight the robust immune response induced by the vaccine, demonstrating its potential to enhance protective immunity against M. bovis in bison through the regulation of Th1/Th2/Th17 differentiation, cell adhesion, and antigen presentation.