Live Bovine Respiratory Syncytial Virus Research Articles

Effects of vitamin E supplementation on serum oxidative stress biomarkers, antibody titer after live bovine respiratory syncytial virus vaccination, as well as serum and fecal immunoglobulin A in weaned Japanese Black calves

The purpose of this study was to determine the effects of vitamin E supplementation on blood oxidative stress biomarker in weaned calves. Thirty clinically healthy 12 weeks of age Japanese Black calves were randomly assigned to two groups: 15 calves received 300 IU of vitamin E daily from 12 to 18 weeks of age (VE group), and the other 15 calves did not receive the vitamin E (control group). Blood samples were taken at 12, 14, 16, 18, and 20 weeks of age. The concentration of serum reactive oxygen metabolites at 20 weeks of age were significantly lower in the VE group than those in the control group. Vitamin E supplementation to weaned calves might affect blood oxidative stress.

離乳後の黒毛和種子牛におけるビタミンE投与と酸化ストレスバイオマーカー，牛RSウイルスワクチン接種に対する抗体産生への影響

離乳後の黒毛和種子牛におけるビタミンE投与と酸化ストレスバイオマーカー，牛RSウイルスワクチン接種に対する抗体産生への影響

Demonstration of Protection Provided by a Single Dose Modified Live BRSV Vaccine against Virulent BRSV Challenge

Bovine respiratory syncytial virus (BRSV) is an economically important cause of respiratory disease in cattle worldwide. The virus is an important respiratory pathogen in naïve cattle of all ages, but as with other respiratory syncytial viruses, it primarily affects young calves. The virus has also been implicated as one of the viral agents involved in the inducing phase of bovine respiratory disease complex. Efficacy of vaccines developed to protect against BRSV related respiratory disease must be demonstrated in models that exhibit clinically relevant respiratory disease in susceptible cattle. The model used in this trial involves experimental infection with a virulent field isolate of BRSV, resulting in induction of severe clinical disease and associated pneumonic lesions.

Effect of Beta-Carotene Supplementation on the Serum Oxidative Stress Biomarker and Antibody Titer against Live Bovine Respiratory Syncytial Virus Vaccination in Japanese Black Calves.

The purpose of this study was to determine the effect of vaccination and beta-carotene supplementation on blood oxidative stress and antibody response in calves. Thirty Japanese Black calves were randomly assigned to two groups. Fifteen calves received 20 mg of beta-carotene supplemented into their daily provided rations from 2 to 8 weeks of age (BC group), and the other 15 calves did not receive the daily beta-carotene supplement (control group). All calves received a commercially available modified live bovine respiratory syncytial (RS) virus vaccine at 4 and 8 weeks of age. Blood samples were taken at 2, 4, 8, and 12 weeks of age. At 4 weeks of age, the concentration of reactive oxygen metabolites within serum were significantly lower in the BC group than the concentrations measured in the control group. Also at 4 weeks of age, the concentration of biological antioxidant capacity within serum was significantly higher in the BC group than the concentrations measured in the control group. Both groups showed a gradual decrease of antibody titers to live bovine RS virus in the samples taken from 2 to 12 weeks of age. These results confirmed that beta-carotene supplementation decreased oxidative stress. However, beta-carotene supplementation did not affect the antibody response to live bovine RS virus vaccination, perhaps due to the presence of the maternal antibody.

Efficacy of an intranasal modified live bovine respiratory syncytial virus and temperature-sensitive parainfluenza type 3 virus vaccine in 3-week-old calves experimentally challenged with PI3V

Two experimental parainfluenza type 3 virus (PI3V) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of an attenuated live vaccine containing modified live bovine respiratory syncytial virus (BRSV) and temperature-sensitive PI3V in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived calves. Nasal shedding of PI3V was highly significantly reduced in vaccinated calves challenged 10 days or 21 days after vaccination. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against PI3V by challenge 66 days post-vaccination. Vaccination also significantly reduced PI3V excretion after challenge in this study. In both studies, clinical signs after challenge were very mild and were not different between vaccinated and control calves.

Protection against bovine respiratory syncytial virus challenge following a single dose of vaccine in young calves with maternal antibody

Twenty-one young calves with maternally derived antibody to bovine respiratory syncytial virus (BRSV) were divided into three groups of seven, each group balanced for BRSV antibody titre. The calves had...

Immune responses to bovine respiratory syncytial virus (BRSV) following use of an inactivated BRSV-PI3- Mannheimia haemolytica vaccine and a modified live BRSV–BVDV vaccine

Immune responses to bovine respiratory syncytial virus (BRSV) following use of an inactivated BRSV-PI3- Mannheimia haemolytica vaccine and a modified live BRSV–BVDV vaccine

Cytokine responses of bovine dendritic cells and T cells following exposure to live or inactivated bovine respiratory syncytial virus

We compared the effects of live or inactivated bovine respiratory syncytial virus (BRSV) on cytokine production by bovine monocyte-derived dendritic cells (MoDC). We also investigated the response of resting memory CD4(+) T cells to MoDC exposed to both viral preparations. Although BRSV did not appear to replicate in MoDC or to affect expression of major histocompatibility complex (MHC) class I, MHC class II, or CD80/86, a higher percentage of cells exposed to live virus appeared to undergo apoptosis/necrosis. To investigate how the interaction of BRSV with MoDC affects the immune response, a multiplex, real-time, polymerase chain reaction was established to analyze transcription of bovine cytokines. Exposure of MoDC to live BRSV induced more interleukin (IL)-10 mRNA and markedly less IL-12p40 and IL-15 mRNA than did heat-inactivated virus. To determine whether these differences might influence the T cell response, CD4(+) memory T cells primed in vivo were restimulated in vitro by MoDC pulsed with heat-inactivated or live BRSV. Stimulation of CD4(+) T cells induced similar levels of IL-2-and IL-4-like activity and interferon-gamma. These observations suggest that while IL-10, produced by MoDC as a result of exposure to live BRSV, may affect IL-12 and IL-15 synthesis by MoDC, it does not appear to affect the cytokine response of BRSV-specific memory CD4(+) T cells. It is possible, however, that differences in the pattern of cytokines produced by MoDC exposed to live or inactivated virus may influence the development of the primary CD4(+) T cell response in vivo.

T-cell populations responsive to bovine respiratory syncytial virus in seronegative calves

Calves lacking detectable serum antibodies against bovine respiratory syncytial virus (BRSV) were screened for virus-specific T-cell memory. Peripheral blood mononuclear cells were cultured in vitro with live BRSV and analyzed by dual-color flow cytometry for surface expression of CD25 on CD4 +, CD8 +, and γδ T-cells. Significant recall responses were detected in some of the seronegative calves. Modified live BRSV vaccine was administered to these and to a group of non-responding calves. Following vaccination, virus-specific IgG, virus neutralizing antibody, and T-cell recall responses were all elevated more rapidly in the group with BRSV-sensitive T-cells than in the T-cell-negative group, which suggested that calves in the first group were previously exposed to BRSV. This demonstrates that exposure to BRSV can induce T and B cell memory in young calves without causing seroconversion. The calves were presumably exposed to BRSV while they had maternal antibody, which inhibited the calves from developing an antibody response.

Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-γ) production at subsequent infection. Interferon-γ production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV and mock challenge (V/M, n=6); mock vaccination and BRSV challenge (M/C, n=6) or FI-BRSV and BRSV challenge (V/C, n=7). Vaccine was administered twice at a 2-week interval; challenge followed one month later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV, concanavalin A (positive control) or spent media (negative control). Supernatants were assayed for IFN-γ using ELISA. Interferon-γ production by BRSV-stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on day 5 PC ( p<0.015); and increased in M/C calves compared to V/C and V/M calves on day 10 PC ( p<0.015). Over time postchallenge, a significant increase in IFN-γ production by BRSV-stimulated PBMC was seen in M/C calves ( p<0.025) but not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-γ production postchallenge. Decreased IFN-γ production may have contributed to impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves.

The effects of bovine respiratory syncytial on normal ovine lymphocyte responses to mitogens or antigens in vitro

In the present study peripheral blood mononuclear cells (MNC) obtained from normal uninfected lambs were used to study the possible effects of bovine respiratory syncytial virus (BRSV) on lymphocyte responses to the mitogens, phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) in vitro. Live BRSV had a depressive effect on the proliferative responses of normal MNC to PHA, Con A and PWM. Inactivated BRSV and a commercial preparation of prostaglandin E 2 were also found to depress the proliferative responses of normal ovine MNC to PHA but recombinant tumour necrosis factor-alpha (TNF-α) had no such effect. Serum samples obtained from BRSV-infected lambs contained substances inhibitory to PHA-driven lymphocyte blastogenesis. Memory blastogenic responses to border disease virus (BDV) of lymphocytes obtained from lambs previously primed with BDV were significantly reduced when lymphocytes were exposed to infectious BRSV.

Immunization with a peptide derived from the G glycoprotein of bovine respiratory syncytial virus (BRSV) reduces the incidence of BRSV-associated pneumonia in the natural host

Previous reports demonstrate that synthetic peptides corresponding to the amino acid region 174–187 of G glycoprotein from subgroups A and B human respiratory syncytial virus (HRSV), containing a Cys →Ser substitution at position 186, confer complete resistance to immunized BALB/c mice against infection with the respective virus. In this report, we show that a Cysl86 →Ser substituted peptide (BG/174–187) representing the corresponding region of the bovine (B) RSV G glycoprotein conferred complete protection of mice against BRSV challenge, suggesting that the 174–187 region of RSV G glycoproteins constitutes a dominant protective epitope which has been maintained throughout evolution. Furthermore, immunization of calves with peptide BG/174–187 efficiently induced the production of antibodies capable of recognizing both the parental G glycoprotein and peptide BG/174–187. Following challenge with live BRSV, although none of the animals were protected from upper respiratory tract disease, there were little or no gross pneumonic lesions in the four peptide-immunized calves. In contrast, moderate to extensive pneumonic lesions were observed in 2 out of 3 calves in the control group. Our results thus suggest that peptide BG/174–187 efficiently prevented BRSV-associated pneumonia in the natural host. The use of this system as a model is quite promising with regard to the development of a human synthetic vaccine.

Field Trials on a Live Bovine Respiratory Syncytial Virus Vaccine in Calves.

Field trials were carried out in calves using a live bovine respiratory syncytial (BRS) virus vaccine prepared from the attenuated BRS virus, strain rs-52. Two hundred seventy-five and 353 calves were vaccinated intranasally and intramuscularly, respectively. No undesirable postvaccinal reactions were observed in the vaccinated calves. Of the serum neutralizing (SN) antibody negative calves 89.7% (26/29) and 92.8% (90/97) developed SN antibody 1 month after intranasal and intramuscular vaccination, respectively. Most of the calves having SN antibody titers of 1:1 or 1:2 at the time of vaccination showed a significant increase in SN antibody titer. About 70% and 90% of the calves vaccinated intranasally and intramuscularly, respectively, maintained SN antibody for 6 months after vaccination. In a field trial, a natural BRS virus infection occurred about 5 months after the start of the trial. Ten of the 16 unvaccinated control calves showed respiratory symptoms due to BRS virus infection. On the contrary, all of the 68 vaccinated calves exhibited no symptoms at all, indicating efficacy of the vaccine.

A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus probably enhanced by vaccination with modified live vaccine.

A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus (BRSV) on a large beef-fattening farm is described. The outbreak started two days after five- to seven-month-old calves were vaccinated with a modified live BRSV vaccine. The disease ran a very severe course among five- to seven-month-old vaccinated calves, but disease was absent in eight-month-old an older non-vaccinated calves. The presence of IgM antibodies in sera of non-vaccinated calves indicated that BRSV was spreading on the farm between two to 15 days before the day of vaccination. The data indicate that vaccination with modified live vaccine during the course of a natural infection may enhance the severity of disease. The possible pathogenesis of the disease is discussed.