Dexamethasone treatment differentially alters viral shedding and the antibody and acute phase protein response after multivalent respiratory vaccination in beef steers123

Abstract

Our objective was to examine immunosuppression induced by dexamethasone (DEX) administration in cattle on immunological responses to a multivalent respiratory vaccine containing replicating and nonreplicating agents. Steers ( = 32; 209 ± 8 kg) seronegative to infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and parainfluenza-3 virus (PI3V) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute immunosuppression (ACU; 0.5 mg/kg BW DEX intravenously at 1000 h only on d 0), 2) chronic immunosuppression (CHR; 0.5 mg/kg BW DEX intravenously at 1000 h on d -3 to 0), or 3) a control (CON; no DEX). On d -4, steers were fitted with intravenous catheters in the jugular vein and placed into individual stanchions. At 1200 h on d 0, steers were administered a respiratory vaccine containing modified-live virus (MLV) isolates of IBRV, BVDV, BRSV, and PI3V and a (MH) toxoid. On d 4, cattle were transported (177 km) and housed in an isolated outdoor pen. Serum was harvested on d 0, 7, 14, 21, 28, 35, 42, and 56 to determine IBRV-, BVDV-, BRSV-, and PI3V-specific antibody titers and MH whole cell and leukotoxin antibody concentrations. Sera from d -2, 0, 1, 3, 7, and 14 were used to quantify haptoglobin (Hp) concentration and ceruloplasmin (Cp) activity. Nasal swab specimens were collected on d 0, 3, and 14 to determine the presence of IBRV, BVDV, BRSV, and PI3V via PCR analysis. There was a treatment × day interaction ( < 0.01) such that CHR steers had a greater ( ≤ 0.07) BVDV antibody titer on d 14, 21, and 28. Moreover, IBRV-specific antibodies increased beginning on d 14 for CHR and on d 28 for ACU and remained greater through d 56 compared with CON ( ≤ 0.03). Conversely, serum MH whole cell antibody concentration was least ( ≤ 0.06) for CHR from d 7 to 28 and greatest for CON ( ≤ 0.04) on d 56. Treatment altered Hp such that CON exhibited a greater ( < 0.01) Hp concentration than CHR but was not different from ACU ( = 0.16). On d 3, Cp was greatest for CON, intermediate for ACU, and least for CHR (treatment × day; ≤ 0.01). The prevalence of IBRV and BVDV in nasal swabs on d 14 was 67 and 56%, respectively, for CHR; 10 and 10%, respectively, for CON; and 9 and 0%, respectively, for ACU ( ≤ 0.006). Results suggest that CHR allowed increased replication of MLV vaccine agents. Conversely, DEX-induced immunosuppression blunted the acute phase protein and antibody response against the nonreplicating MH toxoid.

Vaccination Management of Beef Cattle

“…Cattle treated with an "acute," "chronic," or "control" stress model, induced by dexamethasone treatment and vaccinated with a multivalent combination respiratory vaccinebacterin, generated different antibody titer responses depending on the antigenspecific antibody evaluated. 33 The leukotoxin-specific antibody response from a M haemolytica toxoid was least in the chronic dexamethasone-challenged steers, intermediate for acute, and greatest for control steers. 33 Conversely, both the BHV-1-and BVDV-specific antibody response from the MLV fraction of the combination vaccine was greatest for chronic dexamethasone-challenged steers, intermediate for acute, and least for control steers.…”

“…33 The leukotoxin-specific antibody response from a M haemolytica toxoid was least in the chronic dexamethasone-challenged steers, intermediate for acute, and greatest for control steers. 33 Conversely, both the BHV-1-and BVDV-specific antibody response from the MLV fraction of the combination vaccine was greatest for chronic dexamethasone-challenged steers, intermediate for acute, and least for control steers. 33 The greater antibody titer for dexamethasone-treated cattle administered MLV is probably a result of much greater replication of the liveattenuated vaccine agents in the immunosuppressed host.…”

“…33 Conversely, both the BHV-1-and BVDV-specific antibody response from the MLV fraction of the combination vaccine was greatest for chronic dexamethasone-challenged steers, intermediate for acute, and least for control steers. 33 The greater antibody titer for dexamethasone-treated cattle administered MLV is probably a result of much greater replication of the liveattenuated vaccine agents in the immunosuppressed host. Therefore, MLV vaccination in high-risk cattle that are immunosuppressed may not be safe, which is a primary rationale for delayed vaccination recommendations.…”

Characterization and comparison of cell-mediated immune responses following ex vivo stimulation with viral and bacterial respiratory pathogens in stressed and unstressed beef calves1

“…Unfortunately, stocker calves experience numerous stressors that could affect the efficacy of vaccination and it has been established that stress can suppress immune function in cattle (Carrasco and Van de Kar, 2003;Charmandari et al, 2005). In addition, stress can also contribute to increased shedding of viral respiratory pathogens (Fulton et al, 2016;Richeson et al, 2016). However, more recent work uses dexamethasone to simulate stress-induced immunosuppression in otherwise healthy cattle with a known health and transportation history (Richeson et al, 2016).…”

“…In addition, stress can also contribute to increased shedding of viral respiratory pathogens (Fulton et al, 2016;Richeson et al, 2016). However, more recent work uses dexamethasone to simulate stress-induced immunosuppression in otherwise healthy cattle with a known health and transportation history (Richeson et al, 2016). Therefore, the objectives of this study were to characterize the cell-mediated immune responses of multiple source, highly commingled calves of unknown health history and compare the responses of these calves to a group of calves that were single source, of a known health history, and weaned for 60 d.…”