Association Between Cytokine Changes and Estrous Cyclicity in Bos Indicus and Bos Indicus-influenced Cattle After Vaccination with an Individual or Combination Modified-live Viral Vaccine Against Bovine herpesvirus-1

Abstract Modified-live viral (MLV) vaccinations containing both Infectious Bovine Rhinotracheitis (IBR) and Bovine Viral Diarrhea Virus (BVDV) agents have been reported to induce oophoritis of the corpus luteum (CL), increase pro-inflammatory cytokine populations, and lead to abnormal estrous cycles. When cattle were vaccinated with a MLV that contained only the BVDV antigen, however, no abnormal cycles were observed. The objectives of this study were twofold: 1) to identify specific cytokine populations elevated following MLV immunization and 2) to evaluate whether MLV vaccines containing the IBR antigen only caused abnormal estrous cycles. Brahman and F1 Brahman cattle that exhibited normal estrous cycles were synchronized with PGF2α on d-3 to regress corpora lutea that were present. Animals were immunized (d0) with one of four respective treatments: 1) MLV containing only IBR (IBR; n = 5), 2) MLV combination vaccine containing both IBR and BVDV (BVDV+IBR; n = 5), 3) inactivated combination viral vaccine containing both IBR and BVDV (IVV; n = 5), or 4) physiological saline (CON; n = 3). Blood samples were collected via venipuncture on d-3, 0, 3, 5, 11, 18, 21, 28, 34, 48, and 62, with plasma and serum harvested for progesterone and cytokine analysis. Plasma samples were analyzed for IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-36RA, MIP-1α, MIP-1β, IP-10, MCP-1, TNF-α, and VEGF-A concentrations using a MILLIPLEX Bovine Cytokine/Chemokine Magnetic Bead Panel. Serum was used to analyze progesterone concentrations via radioimmunoassay to determine estrous cyclicity. Progesterone concentrations 1ng/mL or less prior to d16, were determined to be abnormal. Cattle that received the combination (BVDV+IBR) and individual (IBR) MLV vaccine, experienced 20% (1/5) and 60% (3/5) abnormal cycles, respectively. Differences in cytokine concentrations among animals that had a normal (n = 13) and abnormal (n = 5) cycle after vaccination were analyzed as repeated measures in SAS (v9.4), with cycle, time, and cycle by time included in the model. There was an effect of cycle on IL-1α (P = 0.0002), IL-1β (P = 0.02), IL-4 (P = 0.01), IL-6 (P = 0.056), IL-10 (P = 0.015), IL-17A (P = 0.0002), MIP-1α (P = 0.038), and VEGF-A (P 0.0001). There was a time effect on IFN-γ (P 0.0001), IL-8 (P = 0.0004), IL-17A (P = 0.008), and IL-36RA (P 0.0001), with a cycle by time interaction on IFN-γ (P = 0.002) and IL-8 (P = 0.1). Specifically, IFN-γ was elevated on d3 in cattle that experienced abnormal cycles compared to normal cycles. Concurrently, IL-8, was elevated on d3 and d11 post-vaccination. Overall, the vaccines that contained the IBR antigen had a significant effect on cytokine concentrations post-vaccination and was found to negatively impact luteal function, which can reduce reproductive success. Understanding these effects provides insight for producers on proper vaccination timing to preserve herd fertility and profitability. USDA is an equal opportunity provider and employer.