Prevention of bovine respiratory syncytial virus infection and clinical disease by vaccination

A double blind field trial was carried out with a live attenuated bovine respiratory syncytial virus vaccine. The trial involved 530 calves, two to 10 months old, on 27 dairy farms, where respiratory problems due to bovine respiratory syncytial virus infections had been observed during the preceding year. In 17 herds either all calves were vaccinated (nine groups) or all calves received a placebo (eight groups). In 10 herds half the number of calves were vaccinated and the other half kept as non-vaccinated controls. Calves were vaccinated intramuscularly twice with an interval of four to five weeks. These groups were under regular clinical observation and animals were tested periodically for antibodies to bovine respiratory syncytial virus and parainfluenza type 3 virus. Serological examination indicated that no bovine respiratory syncytial virus infection had occurred prior to the first vaccination in August. Vaccination did not cause adverse reactions. Low concentrations of neutralising and complement fixing antibodies were induced by vaccination and a sharp increase of antibody titres was observed after natural infection of vaccinated animals. Infections with bovine respiratory syncytial virus occurred in six out of eight non-vaccinated groups, in nine out of 10 partly vaccinated groups and in only two out of nine completely vaccinated groups. Virus infection in completely vaccinated groups was significantly reduced compared with partly vaccinated and non-vaccinated groups. The incidence of bovine respiratory syncytial virus lower respiratory disease was significantly reduced in completely vaccinated groups compared to non-vaccinated groups. Generally only mild signs of upper respiratory disease were present in completely vaccinated groups after bovine respiratory syncytial virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of dose, route and virulence of bovine herpesvirus 1 vaccine on experimental respiratory disease in cattle.

Three experiments were conducted with calves in which, following intramuscular or intranasal vaccination with virulent or attenuated bovine herpesvirus 1, calves were protected against bovine herpesvirus 1 -- Pasteurella haemolytica challenge. Calves receiving low doses of vaccine had lower levels of antibody and greater evidence of virus replication upon challenge than those receiving higher doses. In contrast 11/13 unvaccinated controls had fibrino-purulent pneumonia following challenge. The immune response developed later in younger calves and those given low doses of vaccine. Neutralizing antibodies to bovine herpes-virus 1 were not found in nasal secretions, but were present in serum seven days after vaccination. Bovine herpesvirus 1 was isolated before challenge from nasal secretions of calves vaccinated intranasally or intramuscularly with virulent virus but not those vaccinated intramuscularly with vaccine virus. It was concluded that both routes of vaccination with either virulent or attenuated bovine herpesvirus 1 provided protection from challenge with homologous or heterologous bovine herpesvirus 1 and that live vaccines should contain at least 10(3) plaque forming units/dose for effective immunization.     

A bovine respiratory virus vaccination trial

A respiratory virus vaccination trial was carried out in a commercial calf-rearing unit with a history of virus pneumonia. The effects of vaccination on the incidence of virus respiratory disease and growth rate were assessed. Forty-four bought-in calves were allocated to groups and treated as follows: A, unvaccinated controls; B, intranasal temperature-sensitive infectious bovine rhinotracheitis (IBR) vaccine at three and 10 weeks; C, intranasal temperature-sensitive combined IBR and parainfluenza-3 (PI3) vaccine at three and 10 weeks; D, intranasal temperature-sensitive combined IBR and PI3 vaccine at three and 10 weeks plus live attenuated bovine respiratory syncytial (BRS) virus vaccine intramuscularly at seven, 10 and 16 weeks. Two outbreaks of virus pneumonia occurred, one at three to four months of age associated with BRS virus and the other at four to five months of age with PI3 virus. During these outbreaks the incidence of pneumonia was lower and the number of days of elevated temperature and the number of treatments were significantly less in groups vaccinated against the associated virus. Despite these findings there were no significant differences between the growth rates of the groups either during the outbreaks of virus pneumonia or during the 10 month period to slaughter.     

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.     

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.     

Early immunity induced by a glycoprotein E-negative vaccine for infectious bovine rhinotracheitis

Four groups of calves were vaccinated with a glycoprotein E-negative vaccine for infectious bovine rhinotracheitis. Two groups of calves were vaccinated intramuscularly and challenged with a wild-type virus 14 and seven days after being vaccinated. The other two groups were vaccinated intranasally and similarly challenged after four and three days; an unvaccinated control group was also challenged. All four vaccination schedules reduced the incidence of clinical signs and the excretion of wild-type virus, and these reductions occurred as early as three days after the intranasal vaccination even in the absence of neutralising antibodies. Because of its marker characteristics, vaccination with this vaccine would not interfere with the detection of infected cattle during an outbreak, and it should therefore provide a useful tool for emergency vaccination campaigns.     

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.     

Evaluation of efficacy of an inactivated vaccine against bovine respiratory syncytial virus in calves with maternal antibodies

OBJECTIVE: To assess short- and long-term efficacy of an inactivated bovine respiratory syncytial virus (BRSV) vaccine administered i.m. to calves with maternally derived antibodies. ANIMALS: 28 two-week-old calves with neutralizing, maternally derived antibodies against BRSV. PROCEDURE: For evaluation of short-term efficacy, 6 calves were vaccinated i.m. at 2 and 6 weeks of age and challenged intranasally and intratracheally along with a matched group of 4 unvaccinated control calves at 10 weeks of age. For evaluation of long-term efficacy, 2 groups of 6 calves each were vaccinated i.m. at 2, 6, and 18 weeks of age or 14 and 18 weeks of age; these calves were challenged intranasally and intratracheally along with 6 matched unvaccinated control calves at 43 weeks of age. Serum virus neutralizing antibody titer, clinical reactions, and virus shedding in nasal mucus and lung washings were assessed. RESULTS: None of the vaccination regimens resulted in a significant increase in serum virus neutralizing antibody titer. As judged by virus shedding in nasal mucus and lung washings, vaccinated calves were protected against challenge, compared with unvaccinated control groups. Clinical signs attributable to challenge were coughing (short-term efficacy study) and tachypnea and dyspnea (long-term efficacy study). The severity and incidence of disease were significantly lower in the vaccinated groups, compared with that in the unvaccinated groups. CONCLUSIONS AND CLINICAL RELEVANCE: Through vaccination, it is possible to protect vulnerable calves with maternal antibodies against BRSV infection and reduce respiratory tract disease.     

Antibody response of calves to immunoaffinity-purified bovine respiratory syncytial virus VP70 after vaccination and challenge exposure.

Immunoaffinity-purified bovine respiratory syncytial virus (BRSV) fusion (F) protein elicited anti-BRSV-specific antibody responses in BRSV-seronegative calves. After primary vaccination, all calves seroconverted to BRSV as determined by the virus neutralization (VN) test and developed anti-F protein antibodies detectable by protein immunoblot analyses. Subsequent vaccinations induced greater than twofold increase in VN titer in 3 of 9 (33%) calves, and 1 calf became VN-negative, but still had nonneutralizing antibody detectable by protein immunoblot analysis. This calf remained seronegative after challenge exposure. Two groups of calves were vaccinated IM with immunoaffinity-purified BRSV F protein. Each dose was 2 ml containing 20 micrograms of purified F protein. Freund's adjuvants were used for all vaccinations, with Freund's complete adjuvant used for the primary vaccination and Freund's incomplete adjuvant for subsequent vaccinations. The vaccine was administered to both groups at weeks 0 and 3; the first group received a third vaccination at weeks 21. Group-1 and -2 vaccinated calves and non-vaccinated contact controls were intranasally aerosol challenge-exposed with low cell culture-passage BRSV on weeks 22 and 9, respectively. Eight of 9 vaccinated calves did not develop a humoral anamnestic response following challenge exposure, as demonstrated by VN test and protein immunoblot analyses. Calf 14 from group 1 which had a 1:2 VN antibody titer prior to vaccination, was the only calf that developed an anamnestic response.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Immunization against bovine herpesvirus-1 infection. Preliminary tests in calves with a DNA vaccine

A bovine herpesvirus-1 (BHV-1) vaccine expressing glycoprotein D, the form with the transmembrane anchor removed, was evaluated for inducing immunity in calves. The plasmid encoding gD of BHV-1 was injected three times to nine calves, using three animals for each of the following routes: intramuscularly (i.m.), intradermally (i.d.), or intranasally (i.n.). Three additional calves were given the plasmid vector only and served as unvaccinated controls. When calves were subjected to challenge infection with BHV-1, all vaccinated calves as well as the controls developed a typical severe form of infectious bovine rhinotracheitis. However, compared to the controls, the vaccinated calves showed earlier clearance of challenge virus. Moreover, the calves given the vaccine i.m. developed neutralizing antibody to BHV-1 between 21 and 42 days following the first injection of vaccine, whereas in calves vaccinated either i.d. or i.n., as well as the controls, antibody first appeared in their sera 14 days post-challenge infection.     

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.     

Comparative serological response in calves to eight commercial vaccines against infectious bovine rhinotracheitis, parainfluenza-3, bovine respiratory syncytial, and bovine viral diarrhea viruses

A field trial was conducted to compare the serological responses in calves to eight commercial vaccines against infectious bovine rhinotracheitis virus (IBRV), parainfluenza-3 virus (PI3V), bovine respiratory syncytial virus (BRSV), and/or bovine viral diarrhea virus (BVDV). Calves given IBRV, P13V, BRSV, and BVDV vaccines had significantly higher antibodies to these viruses than unvaccinated controls; however, serological responses to killed BVDV vaccines were low. Calves with preexisting antibodies to IBRV, PI3V, BRSV, and the Singer strain of BVDV had lower seroconversion rates following vaccination than calves that were seronegative initially.

Serological responses in calves to IBRV, PI3V, BRSV, and BVDV differed among various commercial vaccines. Antibody titers to IBRV were higher in calves vaccinated with modified-live IBRV vaccines than in those vaccinated with killed IBRV vaccines. Following double vaccination with modified-live IBRV and PI3V vaccines, seroconversion rates and antibody titers to IBRV and PI3V were higher in calves vaccinated intramuscularly than in those vaccinated intranasally. Calves given Cattlemaster 4 had significantly higher titers to BRSV and PI3V, and lower titers to BVDV, than calves given Cattlemaster 3, suggesting that the addition of BRSV to Cattlemaster 4 caused some interaction among antigens.

     

An inactivated parainfluenza virus type 3 vaccine: the influence of vaccination regime on the response of calves and their subsequent resistance to challenge.

Calves maintained in insolated pens were vaccinated with an inactivated parainfluenza virus type (3) (pi3) vaccine usingparenteral and local route singly and in combination. The calves were subsequently monitored for serum antibody response and challenged intranasally with live virus to assess the protection derived from vaccination. Calves receiving one subcutaneous dose of vaccine in oil adjuvant produced a marked antibody response and were partially protected against challenge. Those receiving two successive subcutaneous doses produced a much greater antiboyd response and were completely protected against challenge. One intranasal dose of aqueous vaccine failed elicit a significant serum antibody response or protection against challenge. However, there was some evidence that intranasal vaccination following a single subcutaneous vaccination produced more effective immunity than one subcutaneous dose alone. Thus a vaccination regime was established which protected calves against experimental challenge and which could thefore be used in the field to assess the role of Pi3 virus in calf respiratory disease.     

Protection studies with a globin-enriched protein fraction of Ostertagia ostertagi

The protective capacity of an adult stage Ostertagia ostertagi globin antigen was tested in four vaccination experiments in cattle. In a preliminary experiment, calves were vaccinated three times intraperitoneally with 250 microg globin in Freund's adjuvant and challenged with a trickled infection of 25,000 infective larvae. In three subsequent field studies, calves were vaccinated twice or three times intramuscularly with 80-100 microg globin in Quil A and challenged with a natural gastrointestinal nematode infection on pasture. Higher globin-specific antibody levels were detected in the vaccinated calves than in the control animals in all vaccine trials. In the preliminary experiment, geometric mean cumulative egg counts in the globin group were reduced by 52% and total worm burdens were reduced by 28%, compared to the controls. In the first field trial cumulative faecal egg counts were reduced by 63% in the vaccinated calves. However, the reduction in faecal egg output in these two experiments was not statistically significant and no reduction in faecal egg counts was observed in the vaccinated animals in the two last field trials. In conclusion, vaccination of calves with O. ostertagi globin resulted in highly variable protection levels after challenge infection.     

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.     

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.     

Effects of gastrointestinal parasites on parasite burden, rectal temperature, and antibody titer responses to vaccination and infectious bovine rhinotracheitis virus challenge

Thirty-three colostrum-deprived Holstein bull calves (initial BW of 131 ± 4 kg) were used to determine the effect of timing of anthelmintic administration relative to vaccination on antibody titer response to vaccine component antigens. When calves were at least 3 mo of age, they were sorted randomly into individual pens and assigned to 1 of 3 treatment groups, treatments consisted of 1) dewormed 2 wk before vaccination (DPV), 2) dewormed at the time of vaccination (DV), or 3) control, vaccinated but not dewormed (CONT). All calves were inoculated with infective larvae of brown stomach worms (Ostertagia ostertagi) and intestinal worms (Cooperia spp.) on d 1, 7, 10, 14, and 18 for a total dose of 235,710 infective larvae per calf. Calves (DPV and DV) were dewormed on d 21 or 35 with a 10% fenbendazole suspension at 5 mg/kg of BW. On d 35, all calves were vaccinated with a modified-live virus respiratory vaccine containing IBRV (infectious bovine rhinotracheitis virus), BVDV-1 (bovine viral diarrhea virus genotype 1), BVDV-2 (BVDV genotype 2), PI-3 (parainfluenza-3), and BRSV (bovine respiratory syncytial virus). During the 103-d experiment, weekly fecal egg counts, blood, and rectal temperatures were collected and health status was recorded daily. Blood samples were obtained weekly to determine serum neutralizing (SN) antibody titers to IBRV, BVDV-1, BVDV-2, and PI-3 and cytokine levels for IL-4, IL-6, TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-gamma). There was a tendency (P < 0.09) for CONT calves to have greater IL-4 concentrations. By design, control calves had greater (P < 0.01) fecal egg counts during the experiment. All calves developed antibody titers to IBRV, BVDV-1, BVDV-2, and PI-3 by d 15 postvaccination. On d 88, all calves were challenged with IBRV and blood samples were obtained on d 88, 89, 90, 93, 95, 98, 99, and 103. All calves had increased rectal temperatures during the final 7 d of the IBRV challenge. However, the CONT group had greater (P < 0.01) rectal temperatures on each sampling day except d 90 compared with the DPV and DV treatments. Therefore, deworming before or at vaccination reduced parasite burden and decreased rectal temperature increase after an IBRV challenge. Deworming strategy had no effect on antibody response to vaccination or IBRV challenge.     

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.     

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.