Duration of immunity of a quadrivalent vaccine against respiratory diseases caused by BHV-1, PI3V, BVDV, and BRSV in experimentally infected calves

Several laboratory studies assessed the duration of immunity of a quadrivalent vaccine (Rispoval™4, Pfizer Animal Health) against bovine respiratory diseases (BRD) caused by bovine herpes-virus type-1 (BHV-1), parainfluenza type-3 virus (PI₃V), bovine viral-diarrhoea virus type 1 (BVDV), or bovine respiratory syncytial virus (BRSV). Calves between 7 weeks and 6 months of age were allocated to treatment and then were injected with two doses of either the vaccine or the placebo 3 weeks apart. Six to 12 months after the second injection, animals were challenged with BHV-1 (n = 16), PI₃V (n = 31), BVDV (n = 16), or BRSV (n = 20) and the course of viral infection was monitored by serological, haematological (in the BVDV study only), clinical, and virological means for ≥2 weeks. Infection induced mild clinical signs of respiratory disease and elevated rectal temperature in both vaccinated and control animals and was followed by a dramatic rise in neutralising antibodies in all treatment groups. Titres reached higher levels in vaccinated calves than in control calves after challenge with BHV-1, BVDV, or BRSV. On day 3 after PI₃V challenge, virus shedding was reduced from 3.64 log₁₀ TCID₅₀ in control animals to 2.59 log₁₀ TCID₅₀ in vaccinated animals. On days 6 and 8 after BRSV challenge, there were fewer vaccinated animals (n = 2/10 and 0/10, respectively) shedding the virus than control animals (n = 8/10 and 3/10, respectively). Moreover, after challenge, the mean duration of virus shedding was reduced from 3.8 days in control animals to 1 day in vaccinated animals in the BVDV study and from 3.4 days in control animals to 1.2 days in vaccinated animals in the BRSV study. The duration of immunity of ≥6 months for PI₃V, BHV-1 and BVDV, and 12 months for BRSV, after vaccination with Rispoval™4, was associated mainly with enhanced post-challenge antibody response to all four viruses and reduction of the amount or duration of virus shedding or both.     

Efficacy of a quadrivalent vaccine against respiratory diseases caused by BHV-1, PI3V, BVDV and BRSV in experimentally infected calves

The efficacy of a quadrivalent vaccine against viral bovine respiratory diseases (BRD) was assessed in four experimental studies. Calves between 2 and 9 months of age were allocated to one of two treatment groups (n=9-15) and then received either the vaccine or sterile saline in two doses approximately 3 weeks apart. Three to 5 weeks after the second injection, animals were challenged experimentally with one of the viruses, bovine herpes-virus-1 (BHV-1), parainfluenza type-3 virus (PI(3)V), bovine viral-diarrhoea virus type 1 (BVDV), or bovine respiratory syncytial virus (BRSV) and were then monitored for at least 2 weeks. The administration of the vaccine was associated with enhanced antibody response to all four viruses post-challenge, with the reduction of the amount or duration (or both) of virus shedding in the BHV-1, PI(3)V, BVDV and BRSV studies and with an improvement of some clinical signs in the BHV-1 (nasal discharge, and rectal temperature) and the PI(3)V studies (abnormal respiration, and depression).     

Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in 3-week-old calves experimentally challenged with BRSV

Two experimental bovine respiratory syncytial virus (BRSV) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of a bivalent modified live vaccine containing BRSV in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived (maternal antibody negative) calves 5, 10 and 21 days after vaccination. Nasal shedding of BRSV was significantly reduced in vaccinated calves challenged 10 or 21 days after vaccination. Virus excretion titres were also reduced in vaccinates challenged 5 days after vaccination but reduction in duration of shedding and total amount of virus shed were not statistically significant. Clinical disease after challenge in this study was mild. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against BRSV by challenge 66 days post-vaccination. Vaccination significantly reduced nasal shedding after challenge and the severity of clinical disease was also reduced.     

Acute phase protein changes in calves during an outbreak of respiratory disease caused by bovine respiratory syncytial virus

Bovine acute phase proteins (APPs), lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp) and alpha₁-acid glycoprotein (AGP) were evaluated as inflammatory markers during an outbreak of bovine respiratory disease (BRD) caused by bovine respiratory syncytial virus (BRSV). Calves (n = 10) presented mild to moderate signs of respiratory disease. Secondary bacterial infections, Pasteurella multocida and Mycoplasma dispar as major species, were detected in tracheobronchial lavage samples. Concentrations of SAA and LBP increased at week 1 had the highest values at week 3 and decreased at week 4 of outbreak. Some calves had high Hp concentrations at week 3, but AGP concentrations did not rise during respiratory disease. Higher SAA, LBP and Hp concentrations at a later stage of BRD (week 3) were associated with the low BRSV-specific IgG₁ production, suggesting that these calves had enhanced inflammatory response to the secondary bacterial infection. In conclusion, APPs (especially SAA and LBP) are sensitive markers of respiratory infection, and they may be useful to explore host response to the respiratory infections in clinical research.     

Association of herd BRSV and BHV-1 seroprevalence with respiratory disease and reproductive performance in adult dairy cattle

Background

The aim of this study was to detect the associations between bovine herpesvirus 1 (BHV-1) status of a herd and respiratory disease (BRD) occurrence and reproductive performance in pregnant heifers and cows. The association between management-related factors and higher BRD occurrence was also estimated.

Methods

Serum samples, collected from cows and youngstock from 103 dairy cattle herds, were analyzed for antibodies against BHV-1, bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus (BVDV), and Mycoplasma bovis. A questionnaire was used to collect data concerning herd management factors and reproductive performance, as well as the occurrence of clinical signs of respiratory disease in the last two years, as evaluated by the veterinarian or farm manager. Multiple correspondence analysis (MCA) and logistic regression analysis were performed to identify and quantify the risk factors.

Results

A low to moderate prevalence (1-49%) of BRSV antibodies among youngstock was associated with a high occurrence of respiratory disease (OR = 6.2, p = 0.010) in cows and in-calf heifers. Employees of the farm may participate in the spread of such disease. Larger herd size, loose-housing of cows, housing youngstock separately from cows until pregnancy, and purchasing new animals were factors possibly related to a high occurrence of respiratory disease symptoms in pregnant heifers and cows. The highest risk of abortions (> 1.3%) and increased insemination index (number of inseminations per pregnancy) (> 1.9) occurred in herds with a moderate prevalence of BHV-1 antibodies (1-49%) in cows.

Conclusions

BHV-1 was not associated with acute respiratory disease in adult dairy cattle, however was significantly related to reproductive performance. BRSV possesses the main role in respiratory disease complex in adult dairy cattle.     

Evaluation of practices used to reduce the incidence of bovine respiratory disease in Australian feedlots (to November 2021)

Bovine respiratory disease (BRD) has been identified as the most significant infectious disease of feedlot cattle in eastern Australia.¹ Bovine respiratory disease causes economic loss due to medication costs, mortalities, excessive feed inputs associated with increased time on feed, reduced sale prices and associated labour costs. Bovine respiratory disease is a complex multifactorial condition with multiple animal, environmental and management risk factors predisposing cattle to illness. A range of microorganisms are implicated in BRD with at least four viral and five bacterial species commonly involved individually or in combination. The viruses most commonly associated with BRD in Australia are bovine herpesvirus 1 (BHV1), bovine viral diarrhoea virus (BVDV or bovine pestivirus), bovine parainfluenza 3 virus (PI3) and bovine respiratory syncytial virus (BRSV). More recently, bovine coronavirus has been identified as a potential viral contributor to BRD in Australia.² A number of bacterial species have also been recognised as important to the BRD complex; these include Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes and Mycoplasma bovis. Although one or more of the pathogens listed above can be isolated from clinical cases of BRD, there is no evidence that infection alone causes serious illness. This indicates that, in addition to specific infectious agents, other factors are crucial for the development of BRD under field conditions. These can be categorised as environmental, animal and management risk factors. These risk factors are likely to exert their effects through multiple pathways including reductions in systemic and possibly local immunity. For example, stressors such as weaning, handling at saleyards, transport, dehydration, weather conditions, dietary changes, comingling and pen competition might reduce the effectiveness of the immune system. Reduced immunocompetence can allow opportunistic infection of the lower airways with potential pathogens leading to the development of BRD. The objective of this paper is to critically review the evidence for management practices aimed at reducing the incidence of BRD in Australian feedlot cattle. Predisposing factors (Table 1) largely beyond the control of most feedlots, such as weather and exposure to respiratory viruses, are discussed separately, but these factors can generate indirect prevention responses that are discussed under the preventative practices categories. The current practices are classified as either animal preparation practices (Table 2) or feedlot management practices (Table 3).     

A six-year study on respiratory viral infections in a bull testing facility

Viral infection dynamics and bovine respiratory disease (BRD) treatment rates were studied over six years at a Swedish bull testing station with an 'all in, all out' management system. In August of each of the years 1998-2003, between 149 and 185 4-8-month-old calves arrived at the station from 99 to 124 different beef-breeding herds, and remained until March the following year. Only calves that tested free from bovine viral diarrhoea virus (BVDV) were allowed to enter the station and original animal groups were kept isolated from new cattle in their original herds for three weeks before admission. Although neither prophylactic antibiotics, nor BRD vaccines were used, less than 0.7-13.2% (mean 5%) of the calves (n=970) required treatment for BRD during the first five weeks following entry. This was probably due, at least in part, to the season (the summer months) when the animals were commingled. In the six-month period August-February, 38% of the animals were treated one or more times for BRD and mortality was 0.7%. Hereford and Aberdeen Angus calves had significantly higher treatment rates than Charolais, Simmental and Blonde d'Aquitaine. Serological testing on samples obtained in August, November and January indicated that bovine parainfluenza virus 3 (PIV-3) infections occurred each year before November after entry. Bovine coronavirus (BCoV) infections also occurred every year, but in 3/6 years this was not until after November. Bovine respiratory syncytial virus (BRSV) infections occurred only every second year and were associated with a treatment peak and one death on one occasion (December). The herd remained BVDV free during the entire study period. The infection patterns for PIV-3 and BCoV indicated a high level of infectivity amongst bovine calves, whereas the incidence for BRSV was observed at a lower level. Although the rearing of the animals differed from conventional beef production, the study has shown that commingling animals from many sources is not necessarily associated with high morbidity within the first few weeks after arrival. By preventing BRD soon after commingling the prerequisites for protective vaccination at entry might be improved. Applied management routines are discussed.     

Airborne transmission of BHV1, BRSV, and BVDV among cattle is possible under experimental conditions

To control the diseases caused by bovine herpesvirus 1 (BHV1), bovine respiratory syncytial virus (BRSV), and bovine virus diarrhoea virus (BVDV), it is crucial to know their modes of transmission. The purpose of this study was to determine whether these viruses can be transmitted by air to a substantial extent. Calves were housed in two separate isolation stables in which a unidirectional airflow was maintained through a tube in the wall. In one stable, three of the five calves were experimentally infected with BHV1 and later with BRSV. In the BVDV experiment, two calves persistently infected with BVDV (PI-calves) instead of experimentally infected calves, were used as the source of the virus. In all the calves infections were monitored using virus and antibody detection. Results showed that all the three viruses were transmitted by air. BHV1 spread to sentinel calves in the adjacent stable within three days, and BRSV within nine days, and BVDV spread to sentinel calves probably within one week. Although airborne transmission is possibly not the main route of transmission, these findings will have consequences for disease prevention and regulations in control programmes.     

Seroprevalence of bovine respiratory viruses in North-Western Turkey

Bovine respiratory disease complex is a very important health problem around the world. Present study describes serological distribution of bovine major respiratory viruses in non -vaccinated cattle population of Marmara region in north-western Turkey. Neutralising antibodies specific to bovine viral diarrhoea virus (BVDV), bovine herpesvirus 1 (BHV-1), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (PI-3), bovine adenovirus serotype 1 (BAV-1) and serotype 3 (BAV-3) were investigated. Among 584 serum samples collected from 39 establishments in 7 provinces, 41.4% were positive for BVDV, 17.1% for BHV-1, 73.0% for BRSV, 43.0% for PI-3, 89.5% for BAV-1 and 92.3% for BAV-3. There were significant differences observed between seroprevalence rates detected in neighbouring provinces. Serological prevalence of BVDV, BHV-1 and BRSV were extremely higher in large capacity dairy farms than of small capacity farms (p < 0.0001). This study demonstrates that herd capacity is a very important risk factor for respiratory viruses and, on the other hand bovine adenoviruses and BRSV are the common reason of respiratory diseases in the region.     

The associations of viral and mycoplasmal antibody titers with respiratory disease and weight gain in feedlot calves

Blood samples from 32 groups of calves (n = 700) were taken on arrival and after 28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and 21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and M. bovis, plus data on bovine corona virus (BCV) from a previous study were investigated for their association with the risk of bovine respiratory disease (BRD), and with 28-day weight change, both before and after controlling for titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M. bovis was infrequent, and although exposure to PIV-3 was more common, none of these agents had important associations with BRD. Higher titers to BVDV, BRSV, and BCV on arrival were associated with reduced risks of BRD and increased weight gains. However, there was some variation in these relationships and higher arrival titers to BVDV and BRSV in a subset of the calves were associated with increased risks of BRD. Titer increases to BVDV were associated with a higher risk of BRD and lower weight gains. Titer increases to BRSV were not usually associated with the occurrence of BRD, but titer increases to BRSV in a subset of calves that were vaccinated against BRSV, on arrival, were associated with an elevated risk of BRD. Of all the agents studied, BVDV had the most consistent associations with elevated risk of BRD and lower weight gains. Higher BRSV arrival titers were related to lower risk of BRD and higher weight gains; in some instances titer increases to BRSV were associated with higher BRD risk. Higher titers to BCV on arrival were related to reduced risks of BRD. Practical ways of adequately preventing the negative effects of these agents are still needed.     

Etiology of respiratory disease in non-vaccinated, non-medicated calves in rearing herds

The aim of this study was to examine the occurrence of bacterial, mycoplasmal and viral pathogens in the lower respiratory tract of calves in all-in all-out calf-rearing units. According to clinical status, non-medicated calves with and without respiratory disease signs were selected of the 40 herds investigated to analyse the micro-organisms present in healthy and diseased calves. Tracheobronchial lavage (TBL) and paired serum samples were analysed for bacteria, mycoplasmas, respiratory syncytial virus (RSV), parainfluenza virus 3 (PIV3), bovine corona virus (BCV) and bovine adenovirus (BAV). Pasteurella multocida was the most common bacterial pathogen. It was isolated from 34% of the TBL samples in 28 herds and was associated with clinical respiratory disease (p < 0.05) when other pathogenic bacteria or mycoplasma were present in the sample. Mannheimia spp. and Histophilus somni were rarely found. Mycoplasma bovis was not detected at all. Ureaplasma diversum was associated with clinical respiratory disease (p < 0.05). TBL samples from healthy or suspect calves were more often negative in bacterial culture than samples from diseased calves (p < 0.05). No viral infections were detected in six herds, while 16-21 herds had RSV, BCV, BAV or PIV3. In the herds that had calves seroconverted to BCV, respiratory shedding of BCV was more frequently observed than faecal shedding. This study showed that the microbial combinations behind BRD were diverse between herds. M. bovis, an emerging pathogen in many countries, was not detected.     

Evidence for an immunocompromising effect of bovine pestivirus on bovid herpesvirus 1 vaccination

Five calves were given live intranasal vaccine against bovid herpesvirus 1 (BHV1) two days after intranasal inoculation of bovine pestivirus (BVDV). Another 5 were vaccinated in the absence of BVDV. Control unvaccinated groups were also maintained. All calves were challenged with virulent BHV1. The unvaccinated calves developed signs of infectious bovine rhinotracheitis (IBR) and both vaccinated groups showed a similar degree of clinical protection from IBR. Those given BVDV before vaccination shed up to 140 times more BHV1 (P<0.01) in the nasal mucus following challenge than those which had received BHV1 vaccine alone. The epidemiological significance of this is discussed.     

Serological and molecular diagnosis of bovine viral diarrhoea virus and evidence of other viral infections in dairy calves with respiratory disease in Venezuela

An investigation based on 2 studies was carried out to assess the involvement of bovine virus diarrhoea virus (BVDV), bovine herpesvirus type 1 (BHV-1), and bovine respiratory syncytial virus (BRSV) in calf respiratory disease in dairy farms in Venezuela. In the first study, 8 farms were selected and paired serum samples from 42 calves with respiratory disease were tested by ELISA for antibodies to the 3 viruses. Seroconversion to BVDV, BHV-1, and BRSV was found to 5, 2, and 6 farms out of the 8, respectively. The proportion of calves that showed seroconversion to BVDV, BHV-1, and BRSV were 19%, 14%, and 26%, respectively. In the second study, another farm having previous serological evidence of BVDV infection was selected. The decline of maternal antibodies against BVDV was monitored in 20 calves and the half-life of maternal antibodies was 34 +/- 12 days presumably indicating an early natural infection with BVDV. Furthermore, sera free of BVDV antibodies that were collected in studies 1 and 2 and were assayed for the presence of BVDV by nested RT-PCR. Two BVDV strains were detected and compared to those of ruminant and porcine pestiviruses. Both strains were assigned to subgroup Ib of type I BVDV. This investigation provides information on BVDV genotypes circulating in Venezuela and may contribute to the establishment of official control programmes against the viruses studied.     

A group level analysis of the associations between antibodies to seven putative pathogens and respiratory disease and weight gain in Ontario feedlot calves.

The associations, at the group level, between serological titer to Pasteurella haemolytica surface antigens (Ph), Pasteurella haemolytica cytotoxin (Ph-cytox), infectious bovine rhinotracheitis virus (IBRV), bovine virus diarrhea virus (BVDV), parainfluenza-3 virus (PIV3), respiratory syncytial virus (RSV), Mycoplasma dispar (Md), M. bovis (Mb), and respiratory disease treatment rates, relapse rates, and 28 day weight gains were investigated in 14 groups of calves entering two feedlots during years 1983-1985, in Ontario. Based on least squares regression analyses, seroconversion rates to Mb and BVDV were predictive of increased respiratory disease rates, and seroconversion rates to Ph, Ph-cytox, Md and PIV3 were predictive of decreased weight gains. The R2 for predicting weight gains was much higher than for morbidity rates (0.75 vs 0.47 respectively). Titer data were not predictive of relapse rates. Group level analyses were performed because calves are managed as groups (e.g. pens) in commercial feedlots. Only BVDV seroconversion rates were related to increased risk of respiratory disease at both the individual and group levels of organization. Mycoplasma may be important factors in causing respiratory disease, and their relationship to potentiating the effects of other respiratory pathogens needs further investigation.     

Evidence for an immunocompromising effect of bovine pestivirus on bovid herpesvirus 1 vaccination

Five calves were given live intranasal vaccine against bovid herpesvirus 1 (BHV1) two days after intranasal inoculation of bovine pestivirus (BVDV). Another 5 were vaccinated in the absence of BVDV. Control unvaccinated groups were also maintained. All calves were challenged with virulent BHV1. The unvaccinated calves developed signs of infectious bovine rhinotracheitis (IBR) and both vaccinated groups showed a similar degree of clinical protection from IBR. Those given BVDV before vaccination shed up to 140 times more BHV1 (P less than 0.01) in the nasal mucus following challenge than those which had received BHV1 vaccine alone. The epidemiological significance of this is discussed.     

Experimental infection of calves with bovine respiratory syncytial virus (Quebec strain).

An experiment was designed to evaluate the clinical, haematological, viral and serological aspects of bovine respiratory syncytial virus infection in calves. Eleven calves were inoculated intranasally with bovine respiratory syncytial virus (Quebec strain) in aerosol. Clinical, haemotological and serological responses of the calves and virus shedding were monitored. The experimentally infected animals manifested moderate to severe signs of respiratory disease. The parameters used to evaluate the severity of the disease included ocular discharge, conjunctivitis, lung sounds, nasal discharge, pyrexia and leukopenia. The animals were scored accordingly (scale infected 70.8-148.5, control 22-29.3). Highest disease scores were observed between day 6-9 after infection. Virological and serological assessment demonstrated that the observed clinical picture was due to bovine respiratory syncytial virus infection.     

牛呼吸道合胞体病毒RT-PCR检测方法的建立

根据GenBankTM上发表的牛呼吸道合胞体病毒核衣壳蛋白N基因序列,设计合成了一对特异性引物,扩增大小为596bp的目的片段,通过特异性试验、敏感性试验和重复性试验建立了牛呼吸道合胞体病毒的RT-PCR检测方法。所建立的牛呼吸道合胞体病毒的RT-PCR方法与牛腺病毒、牛副流感病毒、牛传染性鼻气管炎病毒、牛无浆体均无交叉反应,该方法的敏感性可达1TCID50。结果表明,该方法具有快速、敏感、特异性强和重复性好等特点,可作为牛呼吸道合胞体病毒检测的一种方法。     

Serological titers to bovine herpesvirus 1, bovine viral diarrhea virus, parainfluenza 3 virus, bovine respiratory syncytial virus and Pasteurella haemolytica in feedlot calves with respiratory disease: associations with bacteriological and pulmonary cytological variables.

Acute and convalescent serum samples were taken from 59 calves with signs of respiratory disease (cases) and 60 clinically normal animals (controls) during their first month in the feedlot. Sera were analyzed for antibodies to bovine parainfluenza 3 (PI3) virus by hemagglutination inhibition, to bovine viral diarrhea (BVD) virus, bovine respiratory syncytial (BRS) virus and bovine herpesvirus 1 (BHV1) by virus neutralization, and to Pasteurella haemolytica by indirect agglutination (PhIA) and cytotoxin neutralization (PhCN) tests. There was minimal evidence of serological activity to BHV1. Serological activity to the other agents occurred commonly and the prevalence of acute titers and their mean values was similar in case and control groups. Mean convalescent PI3 and P. haemolytica (PhIA) titers were higher in controls than cases (p < 0.01) but, otherwise, convalescent titers did not differ between groups. The incidence of seroconversion was similar in both groups for all agents except for PI3 virus which was more frequent in controls than cases (p < 0.0001). There was a positive association between PhIA and CN seroconversion and isolation of P. haemolytica from bronchoalveolar lavage (BAL) fluid (p < 0.1). The measure of agreement (kappa) between seroconversion with the P. haemolytica PhIA and PhCN tests was 0.51. Bacteriological and cytological evaluations of the respiratory tract were made using BAL. No associations were evident between serological titers and pulmonary cytology. A multivariate logistic analysis was used to evaluate associations between disease status and serological, bacteriological and cytological data. Cases were positively associated with the presence of neutrophils and Pasteurella multocida in BAL fluid and negatively associated with PI3 virus and PhIA seroconversion.     

The role of Mycoplasma bovis in bovine respiratory disease outbreaks in veal calf feedlots

To assess the prevalence and relative importance of Mycoplasma bovis among the pathological agents implicated in bovine respiratory disease (BRD), we surveyed 135 veal calves from nine feedlots in eastern France during naturally occurring outbreaks of respiratory disease. Occurrence of respiratory pathogens, M. bovis, bovine viral diarrhoea (BVD) virus, bovine respiratory syncytial (BRS) virus and parainfluenza-3 (PI3) virus was investigated by seroconversion and isolation of bacteria and viruses from broncho-alveolar fluids. M. bovis and pathogenic respiratory bacteria were isolated in eight of the nine feedlots, and from 106 and 32, respectively, of the 135 tested animals. Seroconversion to PI3 virus occurred in four lots. BVD and BRS viruses were detected in eight and one lot, respectively. M. bovis was the most frequently isolated aetiologic agent in these BRD outbreaks, spreading early and widely throughout the affected units (60-100% rate of isolation and seroconversion). These results stress the importance of M. bovis in the BRD complex.