Safety of a modified-live combination vaccine against respiratory and reproductive diseases in pregnant cows

A combination vaccine (Bovi-Shield FP4 + L5, Pfizer Animal Health) containing modified-live virus (MLV) components against bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus BVDV), parainfluenza virus-3 (PI3), bovine respiratory syncytial virus (BRSV), and inactivated cultures of Leptospira canicola, grippotyphosa, hardjo, icterohaemorrhagiae, and pomona was evaluated for safety in pregnant beef and dairy animals. Heifers vaccinated prebreeding with the minimum immunizing dose (lowest antigen level initiating immunizing effects) of the vaccine's MLV BHV-1 or BVDV components and during pregnancy (approximately 200 days of gestation) with vaccine containing 10x doses of the same BHV-1 and BVDV components delivered live, healthy calves that were determined to be serologically negative (titer less than 1:2) for neutralizing antibodies to BHV-1 and BVDV prior to nursing. Additionally, in three field safety studies, previously vaccinated cows and heifers that received a field dose (vaccine containing antigen levels required for commercial sale of the MLV combination vaccine during either the first, second, or third trimester of pregnancy had abortion rates similar to those of pregnant cows and heifers vaccinated during the same stage of pregnancy with sterile water diluent.     

Prevention of persistent infection in calves by vaccination of dams with noncytopathic type-1 modified-live bovine viral diarrhea virus prior to breeding

OBJECTIVE: To determine the ability of a modified-live virus (MLV) bovine viral diarrhea virus (BVDV) type 1 (BVDV1) vaccine administered to heifers prior to breeding to stimulate protective immunity that would block transmission of virulent heterologous BVDV during gestation, thus preventing persistent infection of a fetus. ANIMAL: 40 crossbred Angus heifers that were 15 to 18 months old and seronegative for BVDV and 36 calves born to those heifers. PROCEDURE: Heifers were randomly assigned to control (n = 13) or vaccinated (27) groups. The control group was administered a multivalent vaccine where-in the BVDV component had been omitted. The vaccinated heifers were administered a single dose of vaccine (IM or SC) containing MLV BVDV1 (WRL strain). All vaccinated and control heifers were maintained in pastures and exposed to BVDV-negative bulls 21 days later. Thirty-five heifers were confirmed pregnant and were challenge exposed at 55 to 100 days of gestation by IV administration of virulent BVDV1 (7443 strain). RESULTS: All control heifers were viremic following challenge exposure, and calves born to control heifers were persistently infected with BVDV. Viremia was not detected in the vaccinated heifers, and 92% of calves born to vaccinated heifers were not persistently infected with BVDV. CONCLUSIONS AND CLINICAL RELEVANCE: These results document that vaccination with BVDV1 strain WRL protects fetuses from infection with heterologous virulent BVDV1.     

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.     

Vaccination of pregnant ewes against infection with Salmonella Brandenburg

AIMS: To develop a challenge model for Salmonella Brandenburg infection in pregnant ewes. To compare efficacies of a live attenuated Salmonella Typhimurium mutant, a subunit preparation from a virulent S. Brandenburg isolate, and a commercial multivalent inactivated vaccine in their ability to prevent experimental S. Brandenburg infection. To assess the efficacy of the live attenuated S. Typhimurium mutant against natural S. Brandenburg infection in lambs. METHODS: Two-year-old ewes were immunised with either a live attenuated vaccine (eye-drop; n=20), a subunit vaccine (n=20) or an inactivated bacterin vaccine (n=20), both administered subcutaneously, or served as unvaccinated controls (n=21). Four weeks later, the sensitising regime was repeated as a booster vaccination, and the ewes were challenged 6 weeks later with a virulent S. Brandenburg isolate, approximately 6 weeks prior to lambing. The presence of clinical signs, abortion or death was noted following challenge. The presence and number of Salmonella spp in faecal samples taken throughout the trial, and in organs collected post mortem, were determined using an enrichment selection procedure, and confirmed by serology and pulsed-field gel electrophoresis (PFGE). Half of the surviving lambs were vaccinated with the live attenuated vaccine and all (n=39) were exposed to natural infection from contaminated pasture. RESULTS: There was no significant protection against mortality and abortion following vaccination with the live attenuated, subunit and inactivated vaccines following experimental challenge with S. Brandenburg. There was a significant but transient decrease in the number of ewes shedding S. Brandenburg (live attenuated, p=0.05; subunit, p=0.05; inactivated, p=0.01), and in the quantity of these bacteria in the sheep from the vaccinated groups (p<0.05) compared with controls, 6 weeks after challenge. Lambs from the challenged ewes did not shed Salmonella spp after being vaccinated with the live attenuated vaccine, in contrast to some of the controls, when grazed on pasture contaminated with S. Brandenburg. CONCLUSIONS: The use of live attenuated, subunit and inactivated vaccines did not significantly protect sheep against lethal experimental challenge with S. Brandenburg.     

Fetal protection against continual exposure to bovine viral diarrhea virus following administration of a vaccine containing an inactivated bovine viral diarrhea virus fraction to cattle

OBJECTIVE: To evaluate the efficacy of a commercially available killed bovine viral diarrhea virus (BVDV) vaccine to protect against fetal infection in pregnant cattle continually exposed to cattle persistently infected with the BVDV. ANIMALS: 60 crossbred beef heifers and 4 cows persistently infected with BVDV. PROCEDURES: Beef heifers were allocated to 2 groups. One group was vaccinated twice (21-day interval between the initial and booster vaccinations) with a commercially available vaccine against BVDV, and the other group served as nonvaccinated control cattle. Estrus was induced, and the heifers were bred. Pregnancy was confirmed by transrectal palpation. Four cows persistently infected with BVDV were housed with 30 pregnant heifers (15 each from the vaccinated and nonvaccinated groups) from day 52 to 150 of gestation. Fetuses were then harvested by cesarean section and tested for evidence of BVDV infection. RESULTS: 1 control heifer aborted after introduction of the persistently infected cows. Bovine viral diarrhea virus was isolated from 14 of 14 fetuses obtained via cesarean section from control heifers but from only 4 of 15 fetuses obtained via cesarean section from vaccinated heifers; these proportions differed significantly. CONCLUSIONS AND CLINICAL RELEVANCE: A commercially available multivalent vaccine containing an inactivated BVDV fraction significantly reduced the risk of fetal infection with BVDV in heifers continually exposed to cattle persistently infected with BVDV. However, not all vaccinated cattle were protected, which emphasizes the need for biosecurity measures and elimination of cattle persistently infected with BVDV in addition to vaccination within a herd.     

BHV-1 vaccine induces cross-protection against BHV-5 disease in cattle

Protection against BHV-5 disease induced by inactivated BHV-1 or BHV-5 based vaccines was analysed. Two groups of calves were subcutaneously immunized with an inactivated BHV-1 or BHV-5 based vaccine. A third group was not vaccinated and used as control. In the post-vaccination period, we studied the humoral and cellular immune response resulting similar to both groups. The efficacy of the vaccines was tested after intranasal challenge of the calves with a virulent Argentinean BHV-5 isolate (A-663). All control animals developed neurological signs associated with BHV-5 infection and high levels of virus shedding. Calves immunized with the BHV-1 and BHV-5 inactivated vaccines were protected against BHV-5 disease. Our study provides evidence that strongly support the existence of cross-protection between BHV-1 and BHV-5 in calves. Even though this has already been suggested by previous works, this is the first time an exhaustive study of the immune response is performed and typical clinical BHV-5 meningoencephalitis signs are reproduced in an experimental BHV-5 challenge trial.     

Evaluation of fetal protection against experimental infection with type 1 and type 2 bovine viral diarrhea virus after vaccination of the dam with a bivalent modified-live virus vaccine

OBJECTIVE: To evaluate the efficacy of a modified-live virus (MLV) combination vaccine containing type 1 and type 2 bovine viral diarrhea virus (BVDV) in providing fetal protection against challenge with heterologous type 1 and type 2 BVDV. DESIGN: Prospective study. ANIMALS: 55 heifers. PROCEDURE: Heifers were vaccinated with a commercial MLV combination vaccine or given a sham vaccine (sterile water) and bred 47 to 53 days later. Heifers were challenged with type 1 or type 2 BVDV on days 75 to 79 of gestation. Clinical signs of BVDV infection, presence of viremia, and WBC count were assessed for 14 days after challenge. Fetuses were collected on days 152 to 156 of gestation, and virus isolation was attempted from fetal tissues. RESULTS: Type 1 BVDV was not isolated in any fetuses from vaccinated heifers and was isolated in all fetuses from nonvaccinated heifers challenged with type 1 BVDV. Type 2 BVDV was isolated in 1 fetus from a vaccinated heifer and all fetuses from nonvaccinated heifers challenged with type 2 BVDV. CONCLUSIONS AND CLINICAL RELEVANCE: A commercial MLV combination vaccine containing type 1 and type 2 BVDV given to the dam prior to breeding protected 100% of fetuses against type 1 BVDV infection and 95% of fetuses against type 2 BVDV infection. Use of a bivalent MLV vaccine in combination with a comprehensive BVDV control program should result in decreased incidence of persistent infection in calves and therefore minimize the risk of BVDV infection in the herd.     

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.     

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.     

Foetal protection against bovine virus diarrhoea virus after two-step vaccination

In order to assess the efficacy of a two-step vaccination protocol with respect to foetal protection against transplacental infections with bovine virus diarrhoea virus (BVDV) with special attention to BVDV-2 seronegative heifers were vaccinated with an inactivated BVDV-1 vaccine and boostered with a modified live BVDV-1 vaccine after 4 weeks. A second group was left unvaccinated as control. Between days 30 and 120 of pregnancy the heifers of both groups were intranasally challenged with a mixture of BVDV-1 and -2. All heifers of the vaccinated group gave birth to nine clinically healthy, seronegative (precolostral) and BVDV-free calves. In contrast in the control group four BVDV viraemic underdeveloped calves were born. Additionally, one calf was stillborn and another viraemic calf was not viable and died 2 days after birth. All six calves of the control group were viraemic with BVDV-2. This study demonstrated for the first time that two-step vaccination of breeding cattle with a modified live BVDV vaccine 4 weeks after application of an inactivated BVDV vaccine was capable of providing a foetal protection against transplacental infection with BVDV-2.     

Dynamics of bovine herpesvirus type 1 infection in Estonian dairy herds with and without a control programme

Bovine herpesvirus type 1 (BHV-1) is an important bovine pathogen, exacerbating poor health and the productivity of cattle. The aims of this study were to detect the efficacy of vaccination programmes in lowering the seroprevalence of BHV-1 gE within the dairy herd and to follow the dynamics of the infection in non-vaccinated herds with uninfected heifers. A two-year longitudinal study was carried out on seven herds that were vaccinated, and in five herds with uninfected heifers without applying a control programme. After the start of the vaccination programme, calves born remained free from the virus. However, in one herd, 7 per cent (95 per cent CI 2 to 18) of these animals showed antibodies to BHV-1 two years after the first vaccination. A decline in BHV-1 antibody prevalence was found in vaccinating herds. Among the five herds not under the control programme, one experienced active virus spread, although one herd experienced self-clearance of the virus. In the herds with high BHV-1 prevalence, vaccinating all cattle from three months of age twice a year with a commercial inactivated marker vaccine efficiently protected offspring from becoming infected, and lowered the prevalence of BHV-1 within the herd. A small proportion of herds may experience self-clearance of the virus.     

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.     

Foetal Protection against Bovine Virus Diarrhoea Virus after Two‐step Vaccination

In order to assess the efficacy of a two‐step vaccination protocol with respect to foetal protection against transplacental infections with bovine virus diarrhoea virus (BVDV) with special attention to BVDV‐2 seronegative heifers were vaccinated with an inactivated BVDV‐1 vaccine and boostered with a modified live BVDV‐1 vaccine after 4 weeks. A second group was left unvaccinated as control. Between days 30 and 120 of pregnancy the heifers of both groups were intranasally challenged with a mixture of BVDV‐1 and ‐2. All heifers of the vaccinated group gave birth to nine clinically healthy, seronegative (precolostral) and BVDV‐free calves. In contrast in the control group four BVDV viraemic underdeveloped calves were born. Additionally, one calf was stillborn and another viraemic calf was not viable and died 2 days after birth. All six calves of the control group were viraemic with BVDV‐2. This study demonstrated for the first time that two‐step vaccination of breeding cattle with a modified live BVDV vaccine 4 weeks after application of an inactivated BVDV vaccine was capable of providing a foetal protection against transplacental infection with BVDV‐2.     

Evaluation of the efficacy of a modified-live combination vaccine against abortion caused by virulent bovine herpesvirus type 1 in a one-year duration-of-immunity study

This study demonstrated that a multivalent vaccine containing modified-live bovine herpesvirus type 1 (BHV-1) protected pregnant heifers and their fetuses against virulent BHV-1 challenge exposure at 365 days after vaccination. The percentage of abortions or fetal deaths caused by BHV-1 was significantly higher in control heifers (10 of 10 [100.0%]) than BHV-1-vaccinated heifers (three of 19 [15.8%]).     

Fetal protection against bovine viral diarrhoea type 1 virus infection after one administration of a live-attenuated vaccine

A modified-live vaccine has been shown previously to prevent fetal infection with bovine viral diarrhoea virus (BVDV)-2 and, to some extent BVDV-1, when used in association with an inactivated vaccine in a two-step vaccination protocol. In this challenge study, the modified-live vaccine used alone was able to protect 13 heifers between 49 and 96 days of gestation at challenge from leucopenia and virus replication and, for a 4-month period, to prevent fetal infection. The efficacy of the BVDV-1f 22146/Han81 challenge was demonstrated by virus isolation from the fetuses of all nine non-vaccinated, control heifers. However, the small number of heifers tested meant that the vaccination failure rate could be as high as 10% in the field.     

Vaccination of pregnant ewes against infection with Salmonella Brandenburg

AIMS: To develop a challenge model for Salmonella Brandenburg infection in pregnant ewes. To compare efficacies of a live attenuated Salmonella Typhimurium mutant, a subunit preparation from a virulent S. Brandenburg isolate, and a commercial multivalent inactivated vaccine in their ability to prevent experimental S. Brandenburg infection. To assess the efficacy of the live attenuated S. Typhimurium mutant against natural S. Brandenburg infection in lambs.

METHODS: Two-year-old ewes were immunised with either a live attenuated vaccine (eye-drop; n=20), a subunit vaccine (n=20) or an inactivated bacterin vaccine (n=20), both administered subcutaneously, or served as unvaccinated controls (n=21). Four weeks later, the sensitising regime was repeated as a booster vaccination, and the ewes were challenged 6 weeks later with a virulent S. Brandenburg isolate, approximately 6 weeks prior to lambing. The presence of clinical signs, abortion or death was noted following challenge. The presence and number of Salmonella spp in faecal samples taken throughout the trial, and in organs collected post mortem, were determined using an enrichment selection procedure, and confirmed by serology and pulsed-field gel electrophoresis (PFGE). Half of the surviving lambs were vaccinated with the live attenuated vaccine and all (n=39) were exposed to natural infection from contaminated pasture.

RESULTS: There was no significant protection against mortality and abortion following vaccination with the live attenuated, subunit and inactivated vaccines following experimental challenge with S. Brandenburg. There was a significant but transient decrease in the number of ewes shedding S. Brandenburg (live attenuated, p=0.05; subunit, p=0.05; inactivated, p=0.01), and in the quantity of these bacteria in the sheep from the vaccinated groups (p<0.05) compared with controls, 6 weeks after challenge. Lambs from the challenged ewes did not shed Salmonella spp after being vaccinated with the live attenuated vaccine, in contrast to some of the controls, when grazed on pasture contaminated with S. Brandenburg.

CONCLUSIONS: The use of live attenuated, subunit and inactivated vaccines did not significantly protect sheep against lethal experimental challenge with S. Brandenburg.     

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.     

The live attenuated bovine viral diarrhea virus components of a multi-valent vaccine confer protection against fetal infection

Fetal infection with bovine virus diarrhea virus (BVDV) causes severe economic loss and virus spread in cattle. This study investigated the ability of modified live BVDV I and II components of a commercially available modified live virus (MLV) vaccine (Breed-Back FP 10, Boehringer Ingelheim Vetmedica Inc.) to prevent fetal infection and abortion, and therefore the birth of persistently infected animals. Heifers immunized with vaccine 4-8 weeks before insemination showed no adverse effects. All vaccinated animals had seroconverted to BVDV 4 weeks after immunization. Pregnant heifers were divided into two vaccination and two control groups and challenged with type I or II BVDV on days 60-90 of gestation. Seroconversion, clinical signs, immunosuppression, viremia, mortality, abortion rate, and fetal infection were studied. Post-challenge, 6/11 (type I challenged) and 8/11 (type II challenged) vaccinated heifers were free from clinical signs of BVD. Post-challenge clinical signs noted in the vaccinated groups were mild to moderate, while all unvaccinated controls had clinical signs ranging from moderate to severe. Viremia was not detected post-challenge in any of the vaccinated heifers. However, 100% of the controls were BVDV viremic on at least 1 day post-challenge. One of 22 vaccinated heifers had transient leukopenia, whereas 2/8 and 6/7 unvaccinated heifers in control groups I and II, respectively, had transient leukopenia. Type II BVDV infection led to abortion or death in 86% of unvaccinated heifers. The corresponding vaccinated group showed no deaths or abortions. All control group fetuses were infected with BVDV. The test vaccine gave 91% (type I BVDV challenged) and 100% (type II BVDV challenged) protection from fetal infection. This vaccine is safe and effective against fetal infection, abortion (type II BVDV) and the birth of persistently infected animals.     

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.     

Effects of modified-live bovine viral diarrhea virus vaccines containing either type 1 or types 1 and 2 BVDV on heifers and their offspring after challenge with noncytopathic type 2 BVDV during gestation

OBJECTIVE: To compare the efficacy of modified-live virus (MLV) vaccines containing either type 1 bovine viral diarrhea virus (BVDV) or types 1 and 2 BVDV in protecting heifers and their offspring against infection associated with heterologous noncytopathic type 2 BVDV challenge during gestation. DESIGN: Randomized controlled study. ANIMALS: 160 heifers and their offspring. PROCEDURES: After inoculation with a placebo vaccine, 1 or 2 doses of an MLV vaccine containing type 1 BVDV, or 1 dose of an MLV vaccine containing both types 1 and 2 BVDV, heifers were bred naturally and challenge exposed with a type 2 BVDV field isolate between 62 and 104 days of gestation. Pregnancies were monitored; after parturition, virus isolation and immunohistochemical analyses of ear-notch specimens were used to determine whether calves were persistently infected. Blood samples were collected at intervals from heifers for serologic evaluation and virus isolation. RESULTS: Persistent infection was detected in 18 of 19 calves from heifers in the control group and in 6 of 18 calves and 7 of 19 calves from heifers that received 1 or 2 doses of the type 1 BVDV vaccine, respectively. None of the 18 calves from heifers that received the type 1-type 2 BVDV vaccine were persistently infected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the incidence of persistent BVDV infection among offspring from dams inoculated with 1 dose of the MLV vaccine containing types 1 and 2 BVDV was decreased, compared with 1 or 2 doses of the MLV vaccine containing only type 1 BVDV.