Expression of the high-affinity interleukin 2 receptor alpha chain (CD25) was used to monitor antigen-specific activation of T lymphocyte subsets (CD4+, CD8+, and gammadelta T cells) from cattle immunized with modified live bovine herpesvirus-1 (BHV-1). Calves seronegative for BHV-1 were either vaccinated with one dose of modified live vaccine containing BHV-1 or not vaccinated to serve as negative controls. Two animals vaccinated 7 and 5 weeks before the start of the experiment with two doses of modified live vaccine containing BHV-1 served as positive controls. Blood samples were taken from the nonvaccinate group, the positive control group, and the vaccinate group at 0, 21, 35, 60, and 90 days postinoculation (PI). Isolated peripheral blood mononuclear cells from immunized and control animals were incubated for 5 days with and without live BHV-1 ISU99. Compared to the nonvaccinates, a significant (p < 0.05) increase in expression of CD25 by CD4+, CD8+, and gammadelta T lymphocytes from the vaccinate group was detected following in vitro exposure to live BHV-1 after vaccination. This is apparently the first report using live BHV-1 to stimulate lymphocytes in vitro and showing CD8+ T cell activation. Peripheral blood from the positive control animals was depleted of CD4+, CD8+, or gammadelta T lymphocytes prior to incubation with BHV-1 to assess bystander activation in the CD25 expression assay. When incubated with live BHV-1, depletion of CD4+ T cells depressed the expression of CD25 by CD8+ T cells, but not gammadelta T cells. Depleting CD8+ or gammadelta T cells prior to in vitro culture with BHV-1 did not affect the expression of CD25 by the remaining T lymphocyte subsets. Vaccinates were protected from challenge with virulent BHV-1 at 110 days postvaccination compared to nonvaccinates. Expression of CD25 appears to be a useful marker for evaluating induction of antigen-specific T lymphocyte subset responses following vaccination.
Antigenic differences between bovine viral diarrhea virus (BVDV) vaccine strains and field isolates can lead to reduced vaccine efficacy. Historically, antigenic differences among BVDV strains were evaluated using techniques based on polyclonal and monoclonal antibody activity. The most common method for antigenic comparison among BVDV isolates is determination of virus neutralization titer (VNT). BVDV antigenic comparisons using VNT only account for the humoral component of the adaptive immune response, and not cell mediated immunity (CMI) giving an incomplete picture of protective responses. Currently, little data is available regarding potential antigenic differences between BVDV vaccine strains and field isolates as measured by CMI responses. The goal of the current paper is to evaluate two groups of cattle that differed in the frequency they were vaccinated, to determine if similar trends in CMI responses exist within each respective group when stimulated with antigenically different BVDV strains. Data from the current study demonstrated variability in the CMI response is associated with the viral strain used for stimulation. Variability in IFN-γ mRNA expression was most pronounced in the CD4+ population, this was observed between the viruses within each respective BVDV subgenotype in the Group 1 calves. The increase in frequency of CD25+ cells and IFN-γ mRNA expression in the CD8+ and CD335+ populations were not as variable between BVDV strains used for stimulation in the Group 1 calves. Additionally, an inverse relationship between VNT and IFN-γ mRNA expression was observed, as the lowest VNT and highest IFN-γ mRNA expression was observed and vice versa, the highest VNT and lowest IFN-γ mRNA expression was observed. A similar trend regardless of vaccination status was observed between the two groups of calves, as the BVDV-1b strain had lower IFN-γ mRNA expression. Collectively, data from the current study and previous data support, conferring protection against BVDV as a method for control of BVDV in cattle populations is still a complex issue and requires a multifactorial approach to understand factors associated with vaccine efficacy or conversely vaccine failure. Although, there does appear to be an antigenic component associated with CMI responses as well as with humoral responses as determined by VNT.
A total of 2,575 beef heifers (BW = 568 ± 28.1 lb; 258 ± 12.7 kg) at high-risk of developing bovine respiratory disease (BRD) were enrolled in a randomized complete-block design study at a commercial feedlot to evaluate the effect of 3 vaccine programs on health, growth performance, and carcass characteristics. Dates of arrival to the feedyard served as the blocking factor and 10, 3-pen blocks were enrolled in the study (n = 10 replications per vaccine program). Chute- order randomization was used during arrival processing to assign heifers to 1 of 3 vaccine programs that differed by vaccine products or timing of the pentavalent modified-live viral vaccination: 1) Pyramid® 5 and Presponse® SQ during arrival processing (PRE), 2) Titanium® 5 and Nuplura® PH during arrival processing (TNA), and 3) Nuplura® PH during arrival processing with Titanium® 5 delayed until 28 days- on-feed (TND). No booster vaccinations were administered. Overall mortality, BRD morbidity, and BRD treatment success risks did not differ among the vaccine programs (P>0.13). There were numerically fewer mortalities attributable to acute interstitial pneumonia in TNA heifers than the TND and PRE heifers (probability of difference = 0.99 and 1.00, respectively). Mortality attributable to BRD did not differ between vaccine programs (probability of difference < 0.48). Endotoxin concentrations were measured in the Mannheimia haemolytica vaccines, and were lower in Nuplura® PH than Presponse® SQ. An arrival vaccine program implementing Titanium® 5 and Nuplura® PH had similar efficacy on BRD- related health outcomes as vaccinating with Pyramid® 5 and Presponse® SQ. Delaying a pentavalent viral vaccine until 28 days-on-feed did not affect health or growth-performance outcomes in this study.
Mannheimia haemolytica (MH) is the primary bacterium involved with bovine respiratory disease (BRO), and there are differences between how the vaccines which confer immunity against this important pathogen are manufactured. Generally speaking, the bacterin and toxoid components of commercially available MH vaccines are harvested through propagation of whole-cell MH cultures. Nuplura® PH (NUP; Elanco Animal Health, Greenfield, IN) contains both toxoid and cell-associated antigens, but these antigens differ as they are manufactured using recombinant technology and a proprietary purification process. The relative efficacy of vaccine programs incorporating NUP versus products derived from whole-cell MH culture has not been evaluated in a large-pen feedlot setting. The objective of this study was to compare 3 vaccination programs on the health, growth performance, and carcass characteristics of feedlot heifers.
Effective control of bovine viral diarrhea virus (BVDV) requires that vaccination provide a high level of protection not only to the dam, but also to the calf in utero, preventing fetal infection and the development of persistently infected (PI) calves. The objective of this study was to determine if primiparous cows vaccinated with a BVDV modified-live virus vaccine (Titanium® 5 L5 HB, Elanco Animal Health, Greenfield, IN, USA) were protected from fetal infections and the development of PI calves following exposure to virulent non-cytopathic type 1 and 2 BVDV.
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