Enhancement of the immune response and virological protection of calves against bovine herpesvirus type 1 with an inactivated gE-deleted vaccine

Four immunisation protocols based on inactivated and attenuated commercially available marker vaccines for bovine herpesvirus type 1 (BHV-1) were compared. The first group of calves were vaccinated with an attenuated vaccine administered intranasally and an inactivated vaccine injected subcutaneously, four weeks apart; the second group were vaccinated twice with the attenuated vaccine, first intranasally and then intramuscularly; the third group were vaccinated twice subcutaneously with the inactivated vaccine; and the fourth group were vaccinated twice intramuscularly with the attenuated vaccine. A control group of calves were not vaccinated. The cellular and humoral immune responses were highest in the two groups which received at least one injection of the inactivated vaccine. Virological protection was observed in all the vaccinated groups after a challenge infection and reactivation by treatment with dexamethasone, but the calves which received one dose of the inactivated vaccine as a booster or two doses of the inactivated vaccine excreted significantly less of the challenge virus than the calves which were vaccinated only with the attenuated preparation.     

ISCOM of BHV-1 envelope glycoproteins protected calves against both disease and infection.

A subunit vaccine in the form of immunostimulating complex (iscom) was prepared to contain the envelope glycoproteins of bovine herpesvirus type 1 (BHV-1). This iscom preparation was tested in a vaccination experiment on 4-month-old calves seronegative to BHV-1. In this experiment, four groups with three animals per group were used. Two groups were vaccinated with the iscom preparation twice, four weeks apart, one group with 50 micrograms and the other with 100 micrograms per calf. The third group received a commercial inactivated whole-virus vaccine applying the same vaccination program. The fourth group served as control. Two weeks after the second vaccination, all the animals were challenge-infected intranasally with a virulent BHV-1 strain and four days later with a virulent Pasteurella multocida--this in order to mimic hard field conditions. When exposed to challenge infection, all the animals vaccinated with the iscom were fully protected, i.e., no virus could be recovered from their nasal secretions and no clinical symptoms were recorded. In contrast, the animals vaccinated with the commercial vaccine, responded to challenge with moderate fever and loss of appetite, and virus was isolated from the nasal secretions. The animals in the control group developed severe clinical symptoms. In the sera of iscom-vaccinated animals, the virus neutralization titers reached levels of 1/3500 or higher.     

Vaccination of calves against bovine herpesvirus-1: assessment of the protective value of eight vaccines

Eight separate, but related experiments, were carried out in which groups of six calves were vaccinated with one of eight commercial vaccines. In each experiment the vaccinated calves were subsequently exposed to three calves infected with virulent bovine herpesvirus-1 (BHV-1). In each experiment, all infected donor calves developed a typical severe infectious bovine rhinotracheitis (IBR) infection and excreted virus in their nasal secretions of up to 10(8.00) TCID50/0.1 ml. One live BHV-1 gE-negative vaccine (A) and three modified live vaccines (B, C, D), administered intranasally, all protected against clinical disease. The calves vaccinated with one vaccine (C) also did not excrete virus in the nasal secretions, whereas the calves protected by vaccines A, B and D excreted virus in their nasal secretions but at low titres (10(0.66)-10(1.24) TCID50/0.1 ml). A fourth modified live vaccine (E), given intramuscularly, failed to prevent mild clinical disease in the calves which also excreted virus in the nasal secretions at titre of 10(1.00) TCID50/0.1 ml. An analogous result was given by the calves vaccinated with either of the two inactivated vaccines (F and G) or with a BHV-1 subunit vaccine (H). All calves developed mild clinical signs and excreted virus at titres of 10(2.20)-10(3.12) TCID50/0.1 ml. Calves vaccinated with C vaccine were subsequently given dexamethasone, following which virus was recovered from their nasal secretions. The virus isolates did not cause disease when calves were infected and appeared to be closely related to the vaccine strain.     

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.     

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.     

Induction of antigen-specific T-cell subset activation to bovine respiratory disease viruses by a modified-live virus vaccine

OBJECTIVE: To determine the efficacy of a modified-live virus vaccine containing bovine herpes virus 1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenza virus 3, and bovine viral diarrhea virus (BVDV) types 1 and 2 to induce neutralizing antibodies and cell-mediated immunity in na?ve cattle and protect against BHV-1 challenge. ANIMALS: 17 calves. PROCEDURES: 8 calves were mock-vaccinated with saline (0.9% NaCl) solution (control calves), and 9 calves were vaccinated at 15 to 16 weeks of age. All calves were challenged with BHV-1 25 weeks after vaccination. Neutralizing antibodies and T-cell responsiveness were tested on the day of vaccination and periodically after vaccination and BHV-1 challenge. Specific T-cell responses were evaluated by comparing CD25 upregulation and intracellular interferon-gamma expression by 5-color flow cytometry. Titration of BHV-1 in nasal secretions was performed daily after challenge. Results-Vaccinated calves seroconverted by week 4 after vaccination. Antigen-specific cell-mediated immune responses, by CD25 expression index, were significantly higher in vaccinated calves than control calves. Compared with control calves, antigen-specific interferon-gamma expression was significantly higher in calves during weeks 4 to 8 after vaccination, declining by week 24. After BHV-1 challenge, both neutralizing antibodies and T-cell responses of vaccinated calves had anamnestic responses to BHV-1. Vaccinated calves shed virus in nasal secretions at significantly lower titers for a shorter period and had significantly lower rectal temperatures than control calves. CONCLUSION AND CLINICAL RELEVANCE: A single dose of vaccine effectively induced humoral and cellular immune responses against BHV-1, BRSV, and BVDV types 1 and 2 and protected calves after BHV-1 challenge for 6 months after vaccination.     

牛传染性鼻气管炎活疫苗安全性和免疫保护效果研究

本试验使用牛传染性鼻气管炎弱毒活疫苗进行安全性和免疫保护效果研究,将该疫苗分别接种1月龄犊牛、6~8月龄牛及后备母牛,接种剂量为2 mL(10头份),检验疫苗安全性。将疫苗接种6~8月龄牛,接种剂量为1 mL(1头份),疫苗接种后28 d使用检验用强毒进行攻毒,检验疫苗对攻击用强毒的保护效力。结果表明,不同月龄牛接种疫苗后体温正常,无任何临床可见异常,后备母牛接种疫苗后精神状态及食欲均良好,无流产、死胎及木乃伊胎出现。疫苗接种牛对强毒攻击可产生较好的抵抗力,攻毒保护率达5/5。 研究结果表明,该疫苗对牛安全,且免疫保护效果良好。     

Longevity of protective immunity to experimental bovine herpesvirus-1 infection following inoculation with a combination modified-live virus vaccine in beef calves

OBJECTIVE: To determine whether a combination viral vaccine containing modified-live bovine herpesvirus-1 (BHV-1) would protect calves from infection with a recent field isolate of BHV-1. DESIGN: Randomized controlled trial. ANIMALS: Sixty 4- to 6-month-old beef calves. PROCEDURE: Calves were inoculated with a placebo 42 and 20 days prior to challenge (group 1; n = 10) or with the combination vaccine 42 and 20 days prior to challenge (group 2; 10), 146 and 126 days prior to challenge (group 3; 10), 117 and 96 days prior to challenge (group 4; 10), 86 and 65 days prior to challenge (group 5; 10), or 126 days prior to challenge (group 6; 10). All calves were challenged with BHV-1 via aerosol. Clinical signs, immune responses, and nasal shedding of virus were monitored for 14 days after challenge. RESULTS: Vaccination elicited increases in BHV-1-specific IgG antibody titers. Challenge with BHV-1 resulted in mild respiratory tract disease in all groups, but vaccinated calves had less severe signs of clinical disease. Extent and duration of nasal BHV-1 shedding following challenge was significantly lower in vaccinated calves than in control calves. In calves that received 2 doses of the vaccine, the degree of protection varied with the interval between the last vaccination and challenge, as evidenced by increases in risk of clinical signs and extent and duration of viral shedding. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that this combination vaccine provided protection from infection with virulent BHV-1 and significantly reduced nasal shedding of the virus for at least 126 days after vaccination.     

Neural changes in vaccinated calves challenge exposed with virulent infectious bovine rhinotracheitis virus

Recurrent infection in calves vaccinated with infectious bovine rhinotracheitis-(IBR) modified live virus was induced by dexamethasone (DM) treatment given 49 days after challenge exposure with virulent IBR virus. Nonchallenge-exposed IM and intranasally vaccinated calves did not excrete the virus after DM treatment; however, IM and intranasally vaccinated and subsequently challenge-exposed calves excreted the challenge-exposure virus into the nasal secretions 5 to 11 days and 6 to 10 days after the DM treatment, respectively. The calves were killed 15 to 18 days (experiment 1) and 14 days (experiment 2) and DM treatment was started and then were examined by histopathologic and fluorescent antibody techniques. All DM-treated calves that were inoculated with the vaccinal virus and challenge exposed with the virulent virus developed nonsuppurative trigeminal ganglionitis and encephalitis. On the contrary, the DM-treated nonchallenge-exposed vaccinated calves did not have lesions in the peripheral nervous system and CNS. Infectious bovine rhinotracheitis virus antigens were not observed in tissues of any of the calves examined (experiments 1 and 2) by fluorescent antibody techniques. These observations indicated that the modified live IBR virus neither produced lesions nor induced latent infection and that modified live IBR virus vaccination did not protect the calves against the establishment of a latent infection after their exposure to large doses of the virulent IBR virus.     

Bovine herpesvirus-1 vaccination against experimental bovine herpesvirus-1 and Pasteurella haemolytica respiratory tract infection: onset of protection

The onset of protection offered by intranasal vaccination with attenuated bovine herpesvirus-1 (BHV-1) was studied in 18 calves given a virulent BHV-1 aerosol challenge inoculum and an aerosol challenge exposure to Pasteurella haemolytica. Calves challenge exposed with virus 3, 7, 11, 15, or 19 days after vaccination and challenge exposed 4 days later with Pasteurella haemolytica did not develop viral-bacterial pneumonia, whereas 2 of 3 control calves died of fibrinous bronchopneumonia 40 and 60 hours after the bacterial aerosol and the 3rd control calf had similar lesions. All vaccinated and control calves had detectable amounts of interferon at the time of viral challenge exposure. Protection was observed before detection of neutralizing antibodies to BHV-1 in nasal secretions or in serum. Protection was therefore present from day 3 through day 19 after vaccination, but the mechanism could not be explained completely by neutralizing antibody or interferon.     

Intranasal vaccination of pigs against Aujeszky's disease: comparison with one or two doses of attenuated vaccines in pigs with high maternal antibody titres

Ten-week-old pigs with high levels of maternally derived antibody (MDA) against Aujeszky's disease virus (ADV) were given either a single intranasal vaccination or one or two doses (with an interval of three weeks) of commercially available attenuated ADV vaccines intramuscularly. The pigs did not produce a clear neutralising antibody response to ADV. However, pigs vaccinated intranasally and pigs given two doses of attenuated ADV vaccines were protected against intranasal challenge with virulent ADV two months after the first vaccination. Pigs given one parenteral dose of attenuated ADV vaccine were insufficiently protected. Protection was shown by shorter periods of growth arrest and fever and a greater reduction of virulent virus shedding after challenge in vaccinated pigs than in unvaccinated control pigs. Although intranasal vaccination conferred protection comparable to two parenteral doses of attenuated vaccines, it reduced shedding of virulent virus much more effectively. These results, together with those of other studies, show that intranasal vaccination confers better protection against Aujeszky's disease in pigs with MDA than parenteral vaccination. However, the efficacy of intranasal vaccination also decreases with increasing levels of MDA at the time of vaccination.     

A study on latency in calves by five vaccines against bovine herpesvirus-1 infection

Four bovine herpesvirus-1 (BHV-1) commercial vaccines, three of which (vaccines B, D, E) were modified live vaccines (MLV) and one (vaccine A) identified as a live strain of BHV-1 gE negative, were used for vaccination of calves, using three calves for each vaccine. Three months after vaccination calves were subjected to dexamethasone (DMS) treatment following which virus was recovered from calves inoculated with vaccine B and from those given vaccine D. No virus reactivation was obtained in calves, which received vaccines A or E. The DNA extracted from the two reactivated viruses was subjected to restriction endonuclease analysis. The restriction pattern of the isolate obtained from calves vaccinated with vaccine D differs significantly from that of the original vaccine, whereas the reactivated virus from calves given vaccine B conserved the general pattern of the original vaccine strain. For each reactivated virus in this experiment (B and D) as well as for the isolate obtained from calves vaccinated with a further MLV (vaccine C) in a previous trial, three calves were inoculated. No clinical signs of disease were detected in any of the inoculated calves during the observation period. When the nine calves were exposed 40 days later to challenge infection with virulent BHV-1, they remained healthy and no virus was isolated from their nasal swabbings. These results indicate that some BHV-1 vaccines considered in the project can establish latency in the vaccinated calves, however, the latency does not appear to interfere with the original properties of the vaccines in terms of safety and efficacy.     

Efficacy of a saponin-adjuvanted inactivated respiratory syncytial virus vaccine in calves

The objective of this study was to determine whether a commercially available, saponin-adjuvanted, inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from experimental infection with virulent BRSV. This was a randomized controlled trial comprising 14, 8- to 9-week-old calves seronegative for BRSV Group 1 calves (n = 8) were not vaccinated and group 2 calves (n = 6) were vaccinated on days 0 and 19 with an inactivated BRSV vaccine. All calves were challenged with virulent BRSV on day 46. Clinical signs, arterial PO2, and immune responses were monitored after challenge. Calves were euthanatized on day 54 (8 d after challenge) and lungs were examined for lesions. Vaccination elicited increases in BRSV-specific immunoglobulin (Ig) G and virus neutralizing antibody titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, but no signs of clinical disease and minimal or no pulmonary lesions in vaccinated calves. Arterial blood oxygen values on day 53 (7 d after challenge) in control calves were significantly lower than those in vaccinated calves, which remained within normal limits. Control calves shed BRSV for several days after challenge, whereas BRSV was not detected on deep nasal swabs from vaccinated calves. In summary, the results indicated that this inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus 27 d after vaccination and significantly decreased the prevalence and severity of pulmonary lesions. Efficacy was similar to that reported for other commercial inactivated and modified-live BRSV vaccines.     

Cell-mediated immune response to rabies virus in dogs following vaccination and challenge

Peripheral blood lymphocytes (PBL) from non-vaccinated dogs and from dogs either vaccinated intramuscularly (IM) or subcutaneously (SC) with an inactivated rabies virus vaccine (Rabguard-TC, Norden Laboratories, Lincoln, NE) or intramuscularly with an attenuated rabies virus vaccine (Endurall-R, Norden Laboratories, Lincoln, NE) were exposed in vitro to rabies virus. Blastogenesis of PBL was measured by incorporation of 3H-thymidine into the DNA of proliferating cells in the presence of a suboptimal concentration of phytohemagglutinin (PHA). Following the first vaccination, there was no difference in the blastogenic response of lymphocytes from dogs vaccinated IM with either the inactivated or attenuated rabies virus vaccines. The inactivated rabies vaccine stimulated as great or greater blastogenic response when it was given SC. The PBL from non-vaccinated control dogs were not stimulated by rabies virus. Dogs vaccinated with the inactivated vaccine developed a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus. Nonvaccinated control dogs did not develop a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus.     

牛病毒性腹泻弱毒活疫苗免疫持续期的研究

为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗10^4.5TCID₅₀/头,监测血清抗体效价,进行免疫持续期的确定。在疫苗免疫后的6、9和12个月分别抽取5头免疫组和5头对照组牛采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×10^7.0 TCID₅₀/mL。结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上,攻毒结果显示3个时间点强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6和9个月动物均分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月。     

牛病毒性腹泻病毒弱毒活疫苗免疫持续期的研究

为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗104.5TCID50,监测血清抗体效价,进行免疫持续期的确定。在疫苗免疫后的6个月、9个月和12个月,分别抽取5头免疫组和5头对照组牛,采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×107.0TCID50/mL。结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上。攻毒结果显示,在3个不同时间点进行强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6个月和9个月时动物血清中均能分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月。     

Production of a falcon herpesvirus vaccine.

Ten common kestrels (Falco tinnunculus) were used for this falcon herpes vaccine experiment. Four kestrels were subcutaneously given 1 ml of an attenuated falcon herpesvirus that had originally been isolated from the liver of an American prairie falcon (Falco mexicanus). This virus was then passaged 100 times on chicken embryo fibroblast cells (CEF-cells). Another 4 kestrels were given subcutaneously an inactivated falcon herpesvirus vaccine derived from the same American field strain. This vaccine was concentrated, inactivated by heat and betapropiolactone and emulsified in complete Freund's adjuvans. Two further kestrels served as controls and were not vaccinated. Twenty-one days after vaccination, all 10 kestrels were challenged with passage 3 of the American falcon herpesvirus. The 2 control kestrels died 6 days after challenge and 3 of those given the inactivated herpes vaccine died 9 days after challenge, with typical lesions of herpesvirus inclusion body hepatitis. Before the vaccination experiment, all 10 kestrels were free of serum neutralising antibodies to the falcon herpesvirus. Twenty-one days after vaccination, all 4 kestrels vaccinated with the attenuated vaccine, and one vaccinated with the killed vaccine, had seroconverted, having shown no symptoms to the challenge with a low passage virulent American herpesvirus strain. Following the challenge their antibody titres to falcon herpesvirus increased. No herpesvirus was isolated from any of the cloacal swabs taken during this experiment, indicating that there is no danger for any other birds from the attenuated herpesvirus vaccine. This experiment clearly shows that an attenuated falcon herpesvirus vaccine can protect kestrels from fatal inclusion body hepatitis.     

Studies on the efficacy of intranasal vaccination for the prevention of experimentally induced parainfluenza type 3 virus pneumonia in calves.

The efficacy of intranasal vaccination in preventing or limiting disease of the lower respiratory tract induced by parainfluenza 3 (PI3) virus was evaluated under experimental conditions, using a commercially available live vaccine containing a temperature-sensitive strain of PI3 virus. In a preliminary study four colostrum-deprived calves were vaccinated intranasally at one week and again at two months of age, and two similar calves were given an intranasal placebo. After the second vaccination serum antibodies to PI3 virus were detected in all four vaccinated calves, but not in the control animals. Seventeen days after the second vaccination all six calves were challenged with virulent PI3 virus, and they were killed six days later. The clinical scores and the extent of pulmonary consolidation were reduced in the vaccinated animals; PI3 virus was detected in the upper and lower respiratory tract of the control calves but in none of the vaccinated calves. In a larger scale study with 14 colostrum-fed calves, seven were vaccinated at one week and again at five weeks of age, and seven were given an intranasal placebo. Two weeks after the second vaccination all 14 calves were challenged with virulent PI3 virus. The clinical scores and lung consolidation were significantly reduced in the vaccinated calves in comparison with the controls. Six days after infection, 10 of the 14 calves were killed; PI3 virus was detectable in the nasal secretions of all seven control calves but in only one of the vaccinated animals, and PI3 viral antigen was detected in the lungs of the control calves but not in those of the vaccinated animals. One of the vaccinated calves had developed a severe clinical response after the challenge, but it had only minor lung consolidation when killed.     

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.     

Efficacy of an inactivated respiratory syncytial virus vaccine in calves.

OBJECTIVE: To determine whether an inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from infection with virulent BRSV. DESIGN: Randomized controlled trial. ANIMALS: 27 nine-week-old calves seronegative for BRSV exposure. PROCEDURE: Group-1 calves (n = 9) were not vaccinated. Group-2 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing a minimum immunizing dose of antigen. Group-3 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing an amount of antigen similar to that in a commercial vaccine. All calves were challenged with virulent BRSV on day 42. Clinical signs and immune responses were monitored for 8 days after challenge. Calves were euthanatized on day 50, and lungs were examined for lesions. RESULTS: Vaccination elicited increases in BRSV-specific IgG and virus neutralizing antibody titers and in production of interferon-gamma. Virus neutralizing antibody titers were consistently less than IgG titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, whereas vaccinated calves had less severe signs of clinical disease and less extensive pulmonary lesions. The percentage of vaccinated calves that shed virus in nasal secretions was significantly lower than the percentage of control calves that did, and peak viral titer was lower for vaccinated than for control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus and decreased the severity of pulmonary lesions. Efficacy was similar to that reported for modified-live BRSV vaccines.