Experimental fetal challenge using type II bovine viral diarrhea virus in cattle vaccinated with modified-live virus vaccine.

Nineteen open heifers or cows were vaccinated 45 days prior to breeding with a modified-live bovine viral diarrhea virus (BVDV) vaccine. An additional six animals were not vaccinated and served as controls. All 25 animals were estrus-synchronized and bred. At 75 days of gestation, the 25 pregnant animals were experimentally infected with a type II isolate of BVDV by intranasal inoculation. At 75 days after inoculation, the animals were euthanized and each fetus was removed and retained for sampling. Virus isolation was accomplished from fetal tissues (spleen, thymus, and small intestine). Type II BVDV was isolated from the fetuses collected from all six unvaccinated control animals and from eight of 19 fetuses from vaccinated animals, which were determined to be persistently infected following experimental challenge.

Synergistic effects of concurrent challenge with bovine respiratory syncytial virus and 3-methylindole in calves.

OBJECTIVE: To evaluate the potential synergy between bovine respiratory syncytial virus (BRSV) and 3-methylindole (3MI) in inducing respiratory disease in cattle. ANIMALS: 20 mixed-breed beef calves. PROCEDURE: A 2 X 2 factorial design was used, with random assignment to the following 4 treatment groups: unchallenged control, BRSV challenge exposure (5 X 10(4) TCID50 by aerosolization and 5.5 X 10(5) TCID50 by intratracheal inoculation), 3MI challenge exposure (0.1 g/kg of body weight, PO), and combined BRSV-3MI challenge exposure. Clinical examinations were performed daily. Serum 3MI concentrations, WBC counts, PCV, total plasma protein, and fibrinogen concentrations were determined throughout the experiment. Surviving cattle were euthanatized 7 days after challenge exposure. Pulmonary lesions were evaluated at postmortem examination. RESULTS: Clinical respiratory disease was more acute and severe in cattle in the BRSV-3MI challenge-exposure group than in cattle in the other groups. All 5 cattle in this group and 3 of 5 cattle treated with 3MI alone died or were euthanatized prior to termination of the experiment. Mean lung displacement volume was greatest in the BRSV-3MI challenge-exposure group. Gross and histologic examination revealed that pulmonary lesions were also most severe for cattle in this group. CONCLUSIONS AND CLINICAL RELEVANCE: Feedlot cattle are commonly infected with BRSV, and 3MI is produced by microflora in the rumen of all cattle. Our results suggest that there is a synergy between BRSV and 3MI. Thus, controlling combined exposure may be important in preventing respiratory disease in feedlot cattle.

Protection of pregnant cattle and their fetuses against infection with bovine viral diarrhea virus type 1 by use of a modified-live virus vaccine.

OBJECTIVE: To determine efficacy of a vaccine containing modified-live bovine viral diarrhea virus (BVDV) type 1 for protecting pregnant cows and their fetuses against virulent heterologous BVDV type 1. DESIGN: Randomized controlled cohort study. ANIMALS: 18 yearling beef heifers seronegative for BVDV and negative when tested for BVDV by virus isolation. PROCEDURE: Cattle were randomly assigned to control (unvaccinated; n = 6) or vaccinated (12) groups. Vaccinated heifers were given a combination vaccine containing modified-live BVDV type 1 comprising a cytopathic (NADL) strain. All 18 heifers were then bred and challenge-exposed between 70 and 75 days of gestation with BVDV type 1, administered intranasally. Cattle were monitored, and infection status of offspring was determined after parturition. Antibody concentrations of vaccinated and control heifers were also monitored. RESULTS: All 6 calves from control heifers had positive results on multiple virus isolation tests and were considered persistently infected. In comparison, only 2 calves from vaccinated cows had positive results on virus isolation tests and were considered persistently infected. One vaccinated heifer aborted, but the fetus was not persistently infected, and the abortion was not attributed to BVDV infection. CLINICAL IMPLICATIONS: Analysis of these data indicated that a single dose of a modified-live NADL-derived BVDV type 1 vaccine will confer protection to dams and their fetuses against challenge-exposure to heterologous BVDV type 1 organisms.

Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus.

OBJECTIVE: To determine efficacy of a modified-live type-I isolate of bovine viral diarrhea virus (BVDV) vaccine in protecting calves from infection with a virulent type-II isolate, and to determine which type of immune response (i.e., humoral or cellular) correlates with protection. DESIGN: Prospective study. ANIMALS: 28 neonatal Holstein and Holstein-cross calves. PROCEDURE: Within 18 hours of birth, calves received maternal colostrum or were fed pooled colostrum. On days 7 to 10 after birth, calves were determined to be seropositive (n = 16) or seronegative (12) for antibodies to BVDV on the basis of ELISA and virus neutralization test results. Seropositive and seronegative 10- to 14-day-old calves were then given a combined vaccine that contained a modified-live type-I isolate of BVDV or a similar vaccine that lacked protection against bovine viral diarrhea. All calves were inoculated intranasally approximately 21 days after vaccination with a virulent type-II isolate of BVDV. Clinical and immunologic variables, including clinical scores, rectal temperatures, results of CBC with lymphocyte subset analysis, antibody responses, and cell-mediated immune responses, were monitored for 14 days after inoculation. RESULTS: Seronegative-unvaccinated calves developed severe disease and required euthanasia. Vaccination of seronegative calves with a modified-live type-I isolate had a disease-sparing effect as did passive transfer of colostral antibodies to BVDV. Clinical scores were not significantly different between seropositive-vaccinated and seropositive-unvaccinated calves after viral inoculation. CLINICAL IMPLICATIONS: A single dose of a modified-live type-I isolate of BVDV vaccine protects young calves from clinical signs of disease associated with type-II isolates.

Lesions and distribution of viral antigen following an experimental infection of young seronegative calves with virulent bovine virus diarrhea virus-type II.

During the past several years, acute infections with bovine viral diarrhea virus (BVDV) have been causally linked to hemorrhagic and acute mucosal disease-like syndromes with high mortality. The majority of BVDVs isolated in such cases have been classified as type II on the basis of genetic and antigenic characteristics. It was our objective to examine clinical disease, lesions and potential sites of viral replication, following experimental BVDV type II infection in young calves. On approximately day 35 after birth, calves that had received BVDV-antibody-negative colostrum were infected by intranasal inoculation of 5 x 10(5) TCID50 of BVDV type II isolate 24,515 in 5 mL of tissue culture fluid (2.5 mL/nostril). Calves were monitored twice daily for signs of clinical disease. Approximately 48-72 h after infection, all calves developed transient pyrexia (39.4-40.5 degrees C) and leukopenia. Beginning on approximately day 7 after infection, all calves developed watery diarrhea, pyrexia (40.5-41.6 degrees C), marked leukopenia (> or = 75% drop from preinoculation values), variable thrombocytopenia, and moderate to severe depression. Calves were euthanized on days 10, 11, or 12 after infection due to severe disease. Gross and histological lesions consisted of multifocal bronchointerstitial pneumonia (involving 10%-25% of affected lungs), bone marrow hypoplasia and necrosis, and minimal erosive lesions in the alimentary tract. Immunohistochemical staining for BVDV revealed widespread viral antigen usually within epithelial cells, smooth muscle cells and mononuclear phagocytes in multiple organs, including lung, Peyer's patches, gastric mucosa, thymus, adrenal gland, spleen, lymph nodes, bone marrow, and skin. This BVDV type II isolate caused rapidly progressive, severe multisystemic disease in seronegative calves that was associated with widespread distribution of viral antigen and few gross or histological inflammatory lesions.

Specificity and duration of neutralizing antibodies induced in healthy cattle after administration of a modified-live virus vaccine against bovine viral diarrhea.

OBJECTIVE: To determine the duration for cross-neutralizing antibodies stimulated by administration of a single dose of a modified-live vaccine against bovine viral diarrhea virus (BVDV) to seronegative cattle. ANIMALS: 23 Angus cows seronegative to BVDV. PROCEDURE: Cows were randomly assigned to control (unvaccinated) or test (vaccinated) groups. Eighteen BVDV-seronegative Angus cattle were vaccinated via IM injection with a modified-live BVDV (NADL strain) vaccine and commingled with 5 unvaccinated seronegative cows. Serum was obtained from the cows before vaccination, on the day of vaccination, and 1.5, 3, 6, 9, 12, and 18 months after vaccination. Serum neutralizing antibody tests were performed on samples obtained at each point after vaccination, using a panel of 12 strains of BVDV that, on the basis of reactivity with monoclonal antibodies, were identified as heterologous. RESULTS: Antibodies against all 12 strains of BVDV (which we tested) were detected by use of viral neutralization testing in samples obtained from vaccinated cattle 18 months after vaccination; however, concentration of antibody for some of the strains was low. Nonvaccinated cattle remained seronegative throughout the 18-month study period. CLINICAL IMPLICATIONS: Analysis of these data indicated that modified-live BVDV vaccines could stimulate an antibody response in seronegative cows that was detectable for at least 18 months after vaccination. These antibodies were able to cross neutralize 12 antigenically diverse strains of BVDV.

Effects of perinatal vaccination on humoral and cellular immune responses in cows and young calves.

OBJECTIVE: To examine the effects of perinatal vaccination on cellular and humoral responses in cows and on passive transfer of antibodies and cells to calves, and to assess the role of maternal antibodies in vaccination responses of neonatal calves. DESIGN: Prospective randomized control trial. ANIMALS: 52 beef cows and their calves. PROCEDURES: Assigned cows were vaccinated twice during the last month of gestation. Assigned calves were vaccinated at day 10 after birth. Antibody concentrations and cellular responses to bovine respiratory syncytial virus (BRSV) and bovine herpesvirus type 1 (BHV-1) were measured in blood and colostrum of cows and in blood of calves. Calves were assessed for passive transfer of lymphocytes. RESULTS: At parturition, serum antibody concentrations to BRSV as well as BHV-1- and BRSV-specific blastogenic responses were significantly higher in vaccinated cows. After birth, calves from vaccinated cows had significantly higher concentrations of BRSV-specific serum antibodies, but not BHV-1 specific antibodies. Calves did not develop delayed-type hypersensitivity responses to BRSV. At weaning, lymphocytes from neonatally vaccinated calves had significantly higher values for virus-specific proliferation than did lymphocytes from unvaccinated calves; however, significant differences were not detected between groups after vaccination at weaning. CLINICAL IMPLICATIONS: Administration of modified-live viral vaccines can boost systemic humoral and cellular responses to BRSV and BHV-1 in cows. Neonatal calves can be immunologically primed by vaccination with modified-live virus vaccines. Virus-specific memory cells persist in most calves until weaning.