Effect of supplemental chromium on antibody responses of newly arrived feeder calves to vaccines and ovalbumin.

Two trials were conducted to investigate the effects of supplemental chromium (Cr) from organic sources (Cr chelate and high Cr yeast) on antibody responses of newly arrived feeder calves following vaccination with infectious bovine rhinotracheitis (IBR), para-influenza-3 (PI3), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea (BVD) and Pasteurella haemolytica and ovalbumin (OVA). Using cross bred steer calves purchased at sales in Ontario, vaccines and OVA were given on d 0 and 21 after arrival in the feedlot. Immune responses of calves were measured as serum specific antibody titres against all antigens on d 0 and 28 or d 35. The anti-OVA antibody responses (trial 2) were further investigated by measuring antibody concentrations of calves weekly until d 55 after arrival in the feedlot. Supplemental Cr (0.14 ppm) from an amino acid-chelated source had no effect on antibody responses to IBR, P13 and BRSV, but enhanced (P < 0.05) antibody titres of calves in response to the BVD vaccine on d 28 or d 35. Supplemental Cr from Cr yeast had no effect on antibody titres of calves to any vaccines. Chromium from both sources (trial 1 and 2) had no effect on antibody responses of calves following vaccination with P. haemolytica. However, supplemental Cr (0.75 ppm) from Cr yeast enhanced (P < 0.05) serum antibody responses of calves to OVA during the primary response (d 14) and secondary response (d 35) following immunization. These data confirmed our previous finding that supplemental Cr can enhance humoral immune response of market-transit stressed calves, but its enhancement on vaccine efficacy was antigen-dependent and variable.     

The effect of route and dosage of immunization on the serological response to a Pasteurella haemolytica and Haemophilus somnus vaccine in feedlot calves

The effect of route and dosage of administration on the serological response to a vaccine containing genetically attenuated leukotoxin of Pasteurella haemolytica combined with bacterial extracts of P. haemolytica and Haemophilus somnus (Somnu-Star Ph, Biostar Inc., Saskatoon, Saskatchewan) was evaluated in a controlled field trial in 301 feedlot calves. Vaccination of calves on arrival at the feedlot with Somnu-Star Ph significantly (p < 0.05) increased P. haemolytica and H. somnus serum antibody titers and reduced bovine respiratory disease (BRD) morbidity. A single subcutaneous vaccination with Somnu-Star Ph was as effective in stimulating a humoral antibody response and in reducing BRD morbidity as double vaccination by the intramuscular or the subcutaneous route. Furthermore, there were no swellings or adverse reactions observed with either subcutaneous or intramuscular administration of Somnu-Star Ph.

These results suggest that feedlot calves can be immunized subcutaneously once on arrival with Somnu-Star Ph. Double vaccination was of no added value in this trial, because the majority of BRD morbidity occurred prior to revaccination fourteen days postarrival. Additional larger-sized field trials are needed to monitor the duration of immunity following vaccination and to test the effect of route and dosage of vaccination on mortality.

     

Comparison of two formulations of oxytetracycline given prophylactically to reduce the incidence of bovine respiratory disease in feedlot calves

A trial involving 1,803 feedlot calves was conducted under commercial feedlot conditions in western Canada to compare the relative effectiveness of a new oxytetracycline formulation, administered either intramuscularly (BMI) or subcutaneously (BMS), to a currently available oxytetracycline formulation, administered intramuscularly (LAB), for the prevention of bovine respiratory disease (BRD) in feedlot calves. All experimental treatments were administered upon arrival at the feedlot and again on the third day after arrival.

Over the entire feeding period, there were no significant differences (p≥0.05) in the BRD treatment rates or the BRD relapse rates between either the BMI or BMS groups compared to the LAB group. Similarly, there were no significant differences (p≥0.05) in the BRD treatment rates in the BMI or BMS groups from days 8-14, days 15-90, or days 1-90 of the feeding period compared to the LAB group. However, during the first seven days of the feeding period the BRD treatment rate in the BMI group was 1.55 times (p<0.05) higher than in the LAB group. From days 1-90 and day 1 to the end of the feeding period, the overall mortality rates, BRD mortality rates, and BRD case fatality rates were two to six times lower in the BMS and BMI groups as compared to the LAB group; however, these differences were not statistically significant (p≥0.05).

These data indicate that both the intramuscular and subcutaneous administration of a new oxytetracycline formulation are comparable to the intramuscular administration of a currently available oxytetracycline formulation when given to calves upon arrival at the feedlot.

     

The effect of age at weaning on the health status of bull calves in a feedlot

Incidence of morbidity and mortality in a feedlot were compared among 381 bull calves weaned one month apart (October 3 and November 1). The calves were 156 and 192 days old at weaning in the earlier and later weaned groups, respectively. Following an adjustment period, the calves were fed a mixed finishing diet containing 90% concentrate ad lib for 140 days in a feedlot. The rate of morbidity did not differ significantly between the two weaning groups. Sick calves in the earlier weaned group had a longer treatment period than those in the later weaned group (3.2 vs 1.4 days, p<0.05). Infections of the respiratory tract were the major cause of sickness and most of the respiratory infections occurred in the early stages of the feedlot period. The frequency of respiratory infections was higher among the earlier weaned calves compared with that in the later weaned group (p<0.01) indicating a higher susceptibility to these infections when calves were weaned at younger ages. Bloat was the second most common health problem among the bulls; however, its incidence did not differ between the two groups (p>0.05). The rate of mortality did not differ significantly between the two groups.     

The effect of subunit or modified live bovine herpesvirus-1 vaccines on the efficacy of a recombinant Pasteurella haemolytica vaccine for the prevention of respiratory disease in feedlot calves

The efficacy of a Pasteurella haemolytica vaccine (PhV) administered once to calves within 24 hours of arrival at a feedlot was tested for the ability to prevent morbidity and mortality from all bovine respiratory disease (BRD) and specifically from fibrinous pneumonia mortality. The PhV consisted of two immunizing ingredients: outer membrane proteins extracted from P. haemolytica, plus genetically attenuated leukotoxin produced by recombinant DNA technology. This double blind study was conducted at a large Saskatchewan feedlot using 2,324 high-risk calves purchased at auction markets and kept under typical commercial feedlot conditions. The trial design included four vaccine test groups: 1) PhV and a bovine herpesvirus type-1 (BHV-1) subunit vaccine comprised only of the virus glycoprotein IV (gIV); 2) PhV and a commercial modified live vaccine (MLV) containing BHV-1 and parainfluenza-3 viruses; 3) gIV alone; and 4) MLV alone. Calves were assigned to vaccine groups in a random systematic manner, individually identified, and monitored for 90 days after vaccination. The vaccines were given once, on arrival, to reflect common feedlot practice, although vaccination prior to expected risk would be more appropriate.

The PhV in combination with gIV reduced BRD morbidity by 20% (p < 0.05) compared to gIV alone and 24% (p < 0.05) compared to MLV alone, and reduced BRD mortality by 88% (p < 0.05) and fibrinous pneumonia mortality by 100% (p < 0.05) when compared to either gIV or MLV alone. Vaccination with PhV in combination with MLV significantly reduced the efficacy of the PhV in preventing BRD morbidity, BRD mortality, and fibrinous pneumonia mortality and also reduced the antibody response to P. haemolytica leukotoxin. These results suggest that the MLV interfered with the protective capacity of the PhV.

     

Impact of meloxicam on respiratory virus titers and health outcomes when administered concurrently with a modified live respiratory vaccine in abruptly weaned beef steers

Abruptly weaned crossbred steer calves (N = 271) were used in a randomized, blinded 2-arm clinical trial to assess the impact of a long-acting non-steroidal anti-inflammatory drug on bovine herpesvirus type 1, bovine respiratory syncytial virus, parainfluenza virus type 3, and coronavirus titers and health outcomes when administered concurrently with a modified live respiratory vaccine upon arrival at a feedlot. Treatment groups included a control (saline; n = 135) and an experimental group (injectable meloxicam; n = 136). Viral antibody titers and body weight were measured on arrival, day 7, and day 21, along with a final weight on day 45. Body weight and antibody titers for all viruses increased over time (P < 0.001); however, there were no differences by treatment group or a significant group × time interaction when evaluated using repeated measures analysis of variance. Interestingly, the use of meloxicam was associated with increased treatment risk (P < 0.05). In conclusion, the administration of meloxicam may adversely affect health; however, a decreased vaccine response is likely not a contributing factor.     

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

Summary

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.     

Meta-analysis of field trials of antimicrobial mass medication for prophylaxis of bovine respiratory disease in feedlot cattle

One hundred and seven field trials of prophylactic mass medication for bovine respiratory disease (BRD) in feedlot cattle were reviewed. Meta-analysis is the formal quantitative statistical review process that was used to synthesize the data from randomized field trials and draw conclusions concerning the efficacy of prophylactic mass medication in feedlot calves.

The results of the meta-analysis indicated that prophylactic parenteral mass medication of calves with long-acting oxytetracycline or tilmicosin on arrival at the feedlot would reduce BRD morbidity rates (p < 0.001). There were, however, unreliable data on the effects of mass medication on mortality rates and performance, insufficient data on the most effective treatment regimes, and no valid data on the efficacy of feed and water medication for prophylaxis of BRD.

This review highlights the gaps in our knowledge and points out the need for additional well-designed randomized controlled field trials of adequate size to assess the efficacy and socioeconomic impact of prophylactic mass medication for BRD in feedlot cattle.

     

Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination.

The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvement of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later.     

Effects of 3-methylindole production and immunity against bovine respiratory syncytial virus on development of respiratory tract disease and rate of gain of feedlot cattle

OBJECTIVE: To determine whether immunity against bovine respiratory syncytial virus (BRSV) mitigates the effects of 3-methylindole (3MI) on occurrence of bovine respiratory tract disease (BRD) and rate of gain in feedlot cattle. ANIMALS: 254 mixed-breed beef cattle. PROCEDURE: Cattle were randomly assigned to 1 of 3 groups at the time of arrival at the feedlot. One group was vaccinated with an inactivated BRSV vaccine, another was vaccinated with a modified-live BRSV vaccine, and the third was maintained as unvaccinated control cattle. On days 0 and 28, serum BRSV antibody concentrations were measured, using serum neutralizing and ELISA techniques. Serum 3MI concentrations were measured at feedlot arrival and 3 days later. Cattle were monitored for development of BRD. At slaughter, lungs were evaluated grossly for chronic lesions. RESULTS: Higher serum 3MI concentrations early in the feeding period were associated with lower mean daily gain. Control cattle were more likely to be treated for BRD after day 3, compared with cattle vaccinated with the modified-live BRSV vaccine. Humoral immunity against BRSV did not appear to modify the effect of 3MI on development of BRD or mean daily gain. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abrogating the effects of 3MI and BRSV infection may improve the health and growth performance of feedlot cattle. However, in this study, immunity against BRSV did not appear to protect against the potential synergism between 3MI and BRSV infection, possibly because of the slow rates of gain of cattle included in the study or timing of sample collection.     

Inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves

The effect of maternal antibodies (MatAb) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (BRSV) was addressed for the first time in experimental infection in 34 Holstein calves. Both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute BRSV infection. There were no differences in clinical signs, BRSV shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after BRSV challenge approximately 11 wk after vaccination. There were no anamnestic antibody or cytokine responses in the vaccinates after challenge. Lung lesions were extensive in both groups, and although there was a statistically significant (P = 0.05) difference between groups, this difference was considered not biologically significant. These data indicate that stimulation of protective immune responses was inhibited by maternal antibodies when a combination modified-live BRSV vaccine was administered parenterally to young passively immune calves. Alternate routes of administration or different vaccine formulations should be used to successfully immunize young calves with good passive antibody transfer.     

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.     

A comparison of 2 vaccination programs in feedlot calves at ultra-high risk of developing undifferentiated fever/bovine respiratory disease

The aim of this study was to compare 2 vaccination programs in feedlot calves at ultra-high risk of developing undifferentiated fever (UF)/bovine respiratory disease (BRD). At feedlot arrival, 3882 calves were enrolled in the study and randomly allocated to 2 groups, which were housed by group in 12 pens. At the time of allocation, 1 group (MLV3-BT2) received a multivalent, modified-live viral vaccine containing infectious bovine rhinotracheitis virus (IBRV) and types I and II bovine viral diarrhea virus (BVDV), as well as a Mannheimia haemolytica (MH) and Pasteurella multocida bacterin-toxoid. The other group (MLV4-BT1) received a vaccine containing IIBRV, type I BVDV, bovine respiratory syncytial virus, and parainfluenza-3 virus, as well as a MH bacterin-toxoid. At an average of 69 days post arrival, the groups received their respective viral vaccines. The initial UF treatment, overall chronicity, overall wastage, overall mortality, and BRD mortality rates were significantly (P < 0.05) lower in the MLV3-BT2 group than in the MLV4-BT1 group. Average daily gain and the proportions of yield grade Canada 3 and quality grade E carcasses were significantly (P < 0.05) higher in the MLV3-BT2 group than in the MLV4-BT1 group. No significant (P > or = 0.05) difference in the dry matter intake to gain ratio was detected between the 2 groups. In economic terms, there was a net advantage of $20.86 CDN/animal in the MLV3-BT2 group. This study demonstrates that it is more cost effective to use an MLV3-BT2 vaccination program than a MLV4-BT1 vaccination program in feedlot calves at ultra-high risk of developing UF/BRD.     

Efficacy of parenteral antibiotics for disease prophylaxis in feedlot calves

Trimethoprim-sulfadoxine (TMPSDX) and two formulations of oxytetracycline (OTC) were examined for their prophylactic efficacy in feedlot calves when given by intramuscular injection on arrival at a large commercial feedlot. The study included 2,112 high-risk feeder calves that developed disease early in the feeding period. Both formulations of OTC reduced bovine respiratory disease morbidity during the first two weeks on feed and for the entire feeding period by 15-19% (p<0.05), and they also reduced all fatal fibrinous pneumonia by 67% and 84% (p<0.05). All three drugs significantly reduced all fatal disease in animals first treated during the second week on feed, but not for the overall feeding period. Oxytetracycline with 2-pyrrolidone reduced the incidence of all fatal disease by 44% (p<0.05) during the entire feeding period. The case fatality risk for calves first treated during the second week on feed was lower (p<0.05) in the TMPSDX group and in the OTC with polyvinyl-pyrrolidone group.     

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.     

High mortality rate associated with bovine respiratory syncytial virus (BRSV) infection in Belgian white blue calves previously vaccinated with an inactivated BRSV vaccine

In a group of 60 Belgian White Blue calves less than 8 months old still housed in barns, a bovine respiratory syncytial virus (BRSV) outbreak was revealed on the basis of a direct diagnosis (immunofluorescence and virus isolation) performed on the lungs of dead animals, and the kinetics of BRSV neutralizing antibodies. Clinical signs, macroscopical and microscopical pulmonary lesions were also compatible with a BRSV infection. This outbreak is peculiar because the 35 oldest calves (204 +/- 29 days old) had been vaccinated 3-4 months before with an inactivated BRSV vaccine and 30% of these animals had died of respiratory distress. While they experienced a mild respiratory symptomatology, no death was recorded among the 25 youngest calves (69 +/- 29 days old) which had been left unvaccinated. Another peculiarity was found at the histological level where a massive infiltration of eosinophils was demonstrated in the pulmonary tissues of the dead animals. Together these data parallel the dramatic story described 30 years ago in children previously vaccinated with a formalin-inactivated human RSV (HRSV) vaccine upon a natural HRSV challenge. This illustrates that an immunopathological phenomenon also takes place after BRSV vaccination in cattle.     

A field trial to evaluate the efficacy of a commercial Pasteurella haemolytica bacterial extract in preventing bovine respiratory disease

A double blind, random, controlled field trial was conducted to ascertain the efficacy of a Pasteurella haemolytica bacterial extract (Presponse, Langford Inc., Guelph, Ontario) in the prevention of bovine respiratory disease and/or its effects. Calves from 13 ranches (n = 1140 calves) were assigned to one of four groups, namely: vaccinated at the ranch three weeks prior to shipping to the feedlot; vaccinated only on arrival at the feedlot; vaccinated at both locations; or not vaccinated at either location. Four replicates of auction calves (n = 731) were also assigned to either receive or not receive the vaccine on arrival at the feedlot.

The vaccine did not effect a change in morbidity rates or weight gain. Total mortality rates were increased significantly, and mortality rates from respiratory disease tended to be increased in ranch calves that were vaccinated with Presponse at the ranch. In auction calves, the relapse rates were significantly lower in vaccinated calves. There was a tendency towards a reduction of respiratory disease-related mortality, however there appeared to be no sparing against death from fibrinous pneumonia in auction calves.

     

Effects of a single intranasal dose of modified-live bovine respiratory syncytial virus vaccine on resistance to subsequent viral challenge in calves

OBJECTIVE: To determine whether a single intranasal dose of modified-live bovine respiratory syncytial virus (BRSV) vaccine protects calves from BRSV challenge and characterize cell-mediated immune response in calves following BRSV challenge. ANIMALS: 13 conventionally reared 4- to 6-week-old Holstein calves. PROCEDURES: Calves received intranasal vaccination with modified live BRSV vaccine (VC-group calves; n = 4) or mock vaccine (MC-group calves; 6) 1 month before BRSV challenge; unvaccinated control-group calves (n = 3) underwent mock challenge. Serum virus neutralizing (VN) antibodies were measured on days -30, -14, 0, and 7 relative to BRSV challenge nasal swab specimens were collected for virus isolation on days 0 to 7. At necropsy examination on day 7, tissue specimens were collected for measurement of BRSV-specific interferon gamma (IFN-gamma) production. Tissue distribution of CD3+ T and BLA.36+ B cells was evaluated by use of immunohistochemistry. RESULTS: The MC-group calves had significantly higher rectal temperatures, respiratory rates, and clinical scores on days 5 to 7 after BRSV challenge than VC-group calves. No difference was seen between distributions of BRSV in lung tissue of VC- and MC-group calves. Production of BRSV-specific IFN-gamma was increased in tissue specimens from VC-group calves, compared with MC- and control-group calves. Virus-specific IFN-gamma production was highest in the mediastinal lymph node of VC-group calves. Increased numbers of T cells were found in expanded bronchial-associated lymphoid tissue and airway epithelium of VC-group calves. CONCLUSIONS AND CLINICAL RELEVANCE: An intranasal dose of modified-live BRSV vaccine can protect calves against virulent BRSV challenge 1 month later.     

Interaction of bovine respiratory syncytial virus with bovine alveolar macrophages in vivo: effects of virus infection upon selected cell functions.

The effect of bovine respiratory syncytial virus (BRSV) upon alveolar macrophage (AM) function was investigated using an in vivo calf inoculation model. Alveolar macrophages were collected sequentially from live calves at multiple time points during the 14 day period following viral inoculation. Alveolar macrophages from bronchoalveolar lavage fluids were purified by density gradient centrifugation (> 95% AM) prior to in vitro evaluation of cell functions. There were significant but variable and inconsistent differences in the functions of AM from the BRSV inoculated calves compared to the control calves. Fc-receptor mediated phagocytosis was either increased or unchanged by BRSV inoculation. Nonopsonized phagocytosis was decreased during the early postinoculation period and later increased. There was a variable effect on AM phagosome lysosome fusion with increased fusion activity on postinoculation days 2 through 5, 7 and 12 but reduced activity on days 6 and 10. The AM respiratory burst, as measured by nitroblue tetrazolium dye reduction, was essentially unaffected with a reduction in activity on day 10 only. In this model, BRSV inoculation of calves primarily resulted in an alteration of the membrane associated phagocytic functions of the alveolar macrophages (p < 0.05).     

Response of calves to challenge exposure with virulent bovine respiratory syncytial virus following intranasal administration of vaccines formulated for parenteral administration

OBJECTIVE: To determine whether single-fraction and combination modified-live bovine respiratory syncytial virus (BRSV) vaccines commercially licensed for parenteral administration could stimulate protective immunity in calves after intranasal administration. DESIGN: Randomized controlled trial. ANIMALS: 39 calves. PROCEDURES: Calves were separated from dams at birth, fed colostrum with a minimal concentration of antibodies against BRSV, and maintained in isolation. In 2 preliminary experiments, 9-week-old calves received 1 (n = 3) or 2 (3) doses of a single-component, modified-live BRSV vaccine or no vaccine (8 control calves in each experiment), and were challenged with BRSV 21 days after vaccination. In a third experiment, 2-week-old calves received combination modified-live virus (MLV) vaccines with or without BRSV and calves were challenged with BRSV 8 days later. Calves were euthanized, and lung lesions were measured. Immune responses, including serum and nasal antibody and nasal interferon-alpha concentrations, were assessed. RESULTS: BRSV challenge induced signs of severe clinical respiratory tract disease, including death and pulmonary lesions in unvaccinated calves and in calves that received a combination viral vaccine without BRSV. Pulmonary lesions were significantly less severe in BRSV-challenged calves that received single or combination BRSV vaccines. The proportion of calves that shed virus and the peak virus titer was decreased, compared with control calves. Protection was associated with mucosal IgA antibody responses after challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Single and combination BRSV vaccines administered intranasally provided clinical protection and sparing of pulmonary tissue similar to that detected in response to parenteral delivery of combination MLV and inactivated BRSV vaccines previously assessed in the same challenge model.