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.     

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.     

Efficacy of an inactivated,recombinant bovine herpesvirus type 5 (BoHV-5) vaccine

Bovine herpesvirus type 5 (BoHV-5) is the causative agent of bovine herpetic encephalitis. In countries where BoHV-5 is prevalent, attempts to vaccinate cattle to prevent clinical signs from BoHV-5-induced disease have relied essentially on vaccination with BoHV-1 vaccines. However, such practice has been shown not to confer full protection to BoHV-5 challenge. In the present study, an inactivated, oil adjuvanted vaccine prepared with a recombinant BoHV-5 from which the genes coding for glycoprotein I (gI), glycoprotein E (gE) and membrane protein US9 were deleted (BoHV-5 gI/gE/US9⁻), was evaluated in cattle in a vaccination/challenge experiment. The vaccine was prepared from a virus suspension containing a pre-inactivation antigenic mass equivalent to 10^7.69 TCID₅₀/dose. Three mL of the inactivated vaccine were administered subcutaneously to eight calves serologically negative for BoHV-5 (vaccinated group). Four other calves were mock-vaccinated with an equivalent preparation without viral antigens (control group). Both groups were boostered 28 days later. Neither clinical signs of disease nor adverse effects were observed during or after vaccination. A specific serological response, revealed by the development of neutralizing antibodies, was detected in all vaccinated animals after the first dose of vaccine, whereas control animals remained seronegative. Calves were subsequently challenged on day 77 post-vaccination (pv) with 10^9.25 TCID₅₀ of the wild-type BoHV-5 (parental strain EVI 88/95). After challenge, vaccinated cattle displayed mild signs of respiratory disease, whereas the control group developed respiratory disease and severe encephalitis, which led to culling of 2/4 calves. Searches for viral DNA in the central nervous system (CNS) of vaccinated calves indicated that wild-type BoHV-5 did not replicate, whereas in CNS tissues of calves on the control group, viral DNA was widely distributed. BoHV-5 shedding in nasal secretions was significantly lower in vaccinated calves than in the control group on days 2, 3, 4 and 6 post-challenge (pc). In addition, the duration of virus shedding was significantly shorter in the vaccinated (7 days) than in controls (12 days). Attempts to reactivate latent infection by administration of dexamethasone at 147 days pv led to recrudescence of mild signs of respiratory disease in both vaccinated and control groups. Infectious virus shedding in nasal secretions was detected at reactivation and was significantly lower in vaccinated cattle than in controls on days 11–13 post-reactivation (pr). It is concluded that the inactivated vaccine prepared with the BoHV-5 gI/gE/US9⁻ recombinant was capable of conferring protection to encephalitis when vaccinated cattle were challenged with a large infectious dose of the parental wild type BoHV-5. However, it did not avoid the establishment of latency nor impeded dexamethasone-induced reactivation of the virus, despite a significant reduction in virus shedding after challenge and at reactivation on vaccinated calves.     

Vaccination of calves with contaminated batches of bovine herpes virus 1 vaccines did not result in infection with bovine virus diarrhea virus

The aim of the experiment was to study whether bovine herpesvirus 1 (BHV1) marker vaccine batches known to be contaminated with bovine virus diarrhoea virus (BVDV) type 1 could cause BVD in cattle. For this purpose, four groups of cattle were used. The first group (n = 4 calves, the positive control group), was vaccinated with vaccine from a batch contaminated with BVDV type 2. The second group (n = 4 calves, the negative control group), was vaccinated with vaccine from a batch that was not contaminated with BVDV. The third group (n = 39 calves), was vaccinated with a vaccine from one of four batches contaminated with BVDV type 1 (seronegative experimental group). The fourth group (n = 6 seropositive heifers), was vaccinated with a vaccine from one of three batches known to be contaminated with BVDV type 1. All cattle were vaccinated with an overdose of the BHV1 marker vaccine. At the start of the experiment, all calves except those from group 4 were seronegative for BVDV and BHV1. The calves from group 4 had antibodies against BVDV, were BVDV-free and seronegative to BHV1. After vaccination, the positive control calves became severely ill, had fever for several days, and BVDV was isolated from nasal swabs and white blood cells. In addition, these calves produced antibodies to BVDV and BHV1. No difference in clinical scores of the other groups was seen, nor were BVDV or BVDV-specific antibody responses detected in these calves; however, they did produce antibodies against BHV1. The remainder of each vaccine vial used was examined for the presence of infectious BVDV in cell culture. From none of the vials was BVDV isolated after three subsequent passages. This indicates that BVDV was either absent from the vials or was present in too low an amount to be isolated. Thus vaccination of calves with vaccines from BHV1 marker vaccine batches contaminated with BVDV type 1 did not result in BVDV infections.     

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.     

Characterization of protection from systemic infection and disease by use of a modified-live noncytopathic bovine viral diarrhea virus type 1 vaccine in experimentally infected calves

OBJECTIVE: To evaluate protection against systemic infection and clinical disease provided by use of a modified-live noncytopathic bovine viral diarrhea virus (BVDV) type 1 vaccine in calves challenged with NY-1 BVDV. ANIMALS: 10 calves, 5 to 7 months of age. PROCEDURES: Calves were allocated (n = 5/group) to be nonvaccinated or vaccinated SC on day 0 with BVDV type 1 (WRL strain). Calves in both groups were challenged intranasally with NY-1 BVDV on day 21. Calves' rectal temperatures and clinical signs of disease were recorded daily, total and differential WBC and platelet counts were performed, and serum neutralizing antibody titers against NY-1 BVDV were determined. Histologic examinations and immunohistochemical analyses to detect gross lesions and distribution of viral antigens, respectively, were performed. RESULTS: After challenge exposure to NY-1 BVDV, nonvaccinated calves developed high rectal temperatures, increased respiratory rates, viremia, leukopenia, lymphopenia, and infection of the thymus. Vaccinated calves did not develop high rectal temperatures or clinical signs of respiratory tract disease. Vaccinated calves appeared to be protected against systemic replication of virus in that they did not develop leukopenia, lymphopenia, viremia, or infection of target organs, and infectious virus was not detected in peripheral blood mononuclear cells or the thymus. CONCLUSIONS AND CLINICAL RELEVANCE: The modified-live BVDV vaccine protected calves against systemic infection and disease after experimental challenge exposure with NY-1 BVDV. The vaccine protected calves against infection and viremia and prevented infection of target lymphoid cells.     

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.     

Effect of infectious bovine rhinotracheitis virus immunization on viral shedding in challenge-exposed calves treated with dexamethasone

Calves not vaccinated with infectious bovine rhinotracheitis virus (IBRV) became latently infected when challenge exposed and treated with dexamethasone (DM). Calves that shed IBRV after DM treatment were considered to be latently infected. Vaccination with a temperature-sensitive intranasal vaccine or with formalinized IBRV in Freund's complete adjuvant (IBRV-FCA) protected some, but not all, calves against latent infection--indicating a role for the immune response in preventing latent infection. That all latently infected calves were not detected after DM treatment was indicated by the fact that after a 2nd DM treatment of 3 calves treated 6 months previously and not found to shed virus, 1 of the calves was latently infected. Latently infected calves were inoculated with successive doses of IBRV-FCA and treated with DM. Nonvaccinated calves shed virus, whereas vaccinated calves similarly treated did not shed virus. Because both groups had a comparable cell-mediated immune response, as determined by blastogenic response to IBRV, but the vaccinated group had significantly higher virus-neutralizing antibody titers, a role for humoral antibody in preventing viral shedding was indicated.     

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.     

Effects of hypervaccination with bovine herpesvirus type 1 gE-deleted marker vaccines on the serological response and virological status of calves challenged with wild-type virus

Twenty-four calves were immunised four times with gE-deleted infectious bovine rhinotracheitis marker vaccines before being challenged with small doses of wild-type bovine herpesvirus type 1 (BHV-1). The repeated vaccinations induced strong immunity that prevented detectable virus replication and gE-seroconversion after the challenge infection in most of the calves. The hypervaccinated calves that shed virus after the challenge infection showed no delay in gE-seroconversion compared with unvaccinated control calves. Using a sensitive nested PCR, BHV-1 gE sequences could be detected in the trigeminal ganglia of several of the gE-seronegative, challenge-infected calves, possibly indicating the presence of wild-type BHV-1 DNA.     

A study in calves of an immunologic relationship between herpes simplex virus and Bovid herpesvirus 2

Calves were inoculated subcutaneously with Herpes simplex virus (HSV), types 1 and 2, previously inactivated with Triton X100. Thirty-nine days later the calves were challenged either by intradermal or intravenous injection of Bovid herpesvirus 2 (BHV2).The clinical reponse of HSV preimmunized calves to BHV2 infection was milder than that in the challenge control calves, and the titer of BHV2 underwent a reduction in the preimmunized calves. BHV2 apparently enhanced the immuno-competent system of the preimmunized calves to produce antibody to HSV.From these results it appeared that HSV partially protected calves against experimentally induced BHV2 infection.     

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.     

Attempted reactivation of latent bovine herpesvirus 1 infection in calves by infection with ruminant pestiviruses

Three calves, latently infected with bovine herpesvirus 1 (BHV 1), were each inoculated intranasally with 9 strains of ruminant pestivirus (BVDV). All three calves developed a biphasic pyrexia and a lymphopenia followed by a neutrophilia. They did not shed BHV 1 in their nasal secretions in the 14 days following BVDV inoculation, and their BHV 1 antibody levels remained static, as did those of 2 control calves not given BVDV. All five calves were subsequently shown to be latently infected with BHV 1 by the production of recrudescent infections following the administration of dexamethasone. BHV 1 was recovered from nasal secretions and there was a marked rise in BHV 1 antibody titres in the second week after dexamethasone administration.     

Characterization of protection against systemic infection and disease from experimental bovine viral diarrhea virus type 2 infection by use of a modified-live noncytopathic type 1 vaccine in calves

OBJECTIVE: To evaluate protection resulting from use of a modified-live noncytopathic bovine viral diarrhea virus (BVDV) type 1 vaccine against systemic infection and clinical disease in calves challenged with type 2 BVDV. ANIMALS: 10 calves, 5 to 7 months of age. PROCEDURES: Calves were allocated (n = 5/group) to be nonvaccinated or vaccinated SC on day 0 with BVDV 1 (WRL strain). Calves in both groups were challenged intranasally with BVDV type 2 isolate 890 on day 21. Rectal temperatures and clinical signs of disease were recorded daily, and total and differential WBC and platelet counts were performed. Histologic examinations and immunohistochemical analyses to detect lesions and distribution of viral antigens, respectively, were performed. RESULTS: After challenge exposure to BVDV type 2, nonvaccinated calves developed high rectal temperatures, increased respiratory rates, viremia, leukopenia, lymphopenia, and infection of the thymus. Vaccinated calves did not develop high rectal temperatures or clinical signs of respiratory tract disease. Vaccinated calves appeared to be protected against systemic replication of virus in that they did not develop leukopenia, lymphopenia, viremia, or infection of target organs, and infectious virus was not detected in peripheral blood mononuclear cells or the thymus. CONCLUSIONS AND CLINICAL RELEVANCE: The modified-live BVDV type 1 vaccine protected against systemic infection and disease after experimental challenge exposure with BVDV type 2. The vaccine protected calves against infection and viremia and prevented infection of target lymphoid cells.     

Bovine recombinant interleukin-2 augments immunity and resistance to bovine herpesvirus infection

The in vivo administration of bovine recombinant interleukin-2 (rIL-2) was evaluated in calves vaccinated and then challenged with bovine herpesvirus-1 (BHV-1). In Experiment 1, 24 calves were allotted to four groups: control; bovine rIL-2; BHV-1 vaccine (modified-live); and bovine rIL-2 + BHV-1 vaccine. Serum neutralizing antibody titers to BHV-1 were increased sixfold, and virus shedding was fourfold less in calves vaccinated and treated with rIL-2 (25 micrograms/kg, intramuscularly) when compared to calves that received vaccine only. Treatment with rIL-2 induced lymphokine-activated killer activity that was eliminated by pretreating effector cells with complement and a monoclonal antibody (B26A) specific for the sheep red blood cell receptor. The rIL-2 treatment in BHV-1-vaccinated calves increased the calves' ability to withstand a BHV-1 challenge. However, during treatment with rIL-2, calves developed diarrhea and mild fever that abated after IL-2 treatment was stopped. A second experiment was then conducted to determine a dose of rIL-2 that would enhance immunity to BHV-1 without causing adverse side effects. Twenty-five calves were allotted to five groups that received injections of rIL-2 at 0.0, 25.0, 2.5, 0.25, or 0.025 micrograms kg-1 day-1 for 5 days. All calves received a modified-live BHV-1 vaccine. Calves treated with 25.0 micrograms kg-1 day-1 showed similar adverse side effects as in the first experiment but all other calves were normal. Compared to control calves, those treated with 25.0, 2.5, and 0.25 micrograms kg-1 day-1 of rIL-2 had higher (P less than 0.05) serum antibody titers to BHV-1 and following challenge lower (P less than 0.05) BHV-1 titers in nasal secretions; additionally, clinical disease as evidenced by nasal and ocular discharge was less severe (P less than 0.05). In vitro cytotoxic responses against BHV-1-infected bovine kidney cells were increased (P less than 0.05) in calves treated with rIL-2 in a dose dependent manner. These data suggest that bovine rIL-2 at 2.5 to 0.25 micrograms/kg may be an effective adjuvant to immunization.     

DNA of bovine herpesvirus type 1 in the trigeminal ganglia of latently infected calves

Twelve calves infected with bovine herpesvirus type 1 (BHV-1) were killed when in a latent state of infection. Latency was verified 30 days after virus inoculation of the calves by seroconversion, absence of virus shedding, and in 2 calves, by recrudescence of the infection after they were treated with dexamethasone. By in situ hybridization techniques and autoradiography, DNA of BHV-1 was detected in 13 of 23 trigeminal ganglia of latently infected calves. Viral DNA was restricted to the nucleus of nerve cells. Single neurons harboring BHV-1 DNA were observed in 4.9% of the sections (n = 325) of the trigeminal ganglia. The results obtained correspond to those known from herpes simplex virus infections in mice. The implications for the virus-host relationship are discussed.     

Enhancement of infectious bovine keratoconjunctivitis by modified-live infectious bovine rhinotracheitis virus vaccine

The effects of a modified-live infectious bovine rhinotracheitis virus vaccine (administered ocularly or intranasally) on experimentally induced infectious bovine keratoconjunctivitis were evaluated. The modified-live infectious bovine rhinotracheitis virus vaccine was administered to 13 male Holstein calves (intranasally in 4 and ocularly in 9; day 0). Five calves were not vaccinated and served as controls. Calves were examined daily and, starting on day 4, Moraxella bovis was administered ocularly to all 18 calves once daily for 4 days. The eyes of all calves were assigned a clinical score, and the ocular secretions were evaluated for presence of infectious bovine rhinotracheitis virus and M bovis daily until day 19. The severity of the ocular lesions was estimated by scoring the lesions clinically and by determining the protein concentration, myeloperoxidase activity, and WBC count in the tears. By day 5, conjunctivitis, chemosis, and epiphora were observed in all of the calves vaccinated ocularly. The calves vaccinated intranasally developed conjunctival plaques, but did not develop chemosis or photophobia. All of the calves developed keratitis after inoculation with M bovis. The median lesion scores were greater in both groups of vaccinated calves than in the controls. Corneal perforations developed exclusively in the vaccinated calves. The frequency of M bovis isolation from ocular secretions was significantly (P less than 0.05) greater in the vaccinated calves than in the controls. The tears from the intranasally vaccinated calves contained the highest myeloperoxidase activity and WBC count. The mean protein concentration in the tears of vaccinated calves was not significantly different from that in tears of controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of protection against virulent bovine viral diarrhea virus type 2 in calves that had maternal antibodies and were vaccinated with a modified-live vaccine

OBJECTIVE: To evaluate the efficacy of an adjuvanted modified-live bovine viral diarrhea virus (BVDV) vaccine against challenge with a virulent type 2 BVDV strain in calves with or without maternal antibodies against the virus. DESIGN: Challenge study. ANIMALS: 23 crossbred dairy calves. PROCEDURES: Calves were fed colostrum containing antibodies against BVDV or colostrum without anti-BVDV antibodies within 6 hours of birth and again 8 to 12 hours after the first feeding. Calves were vaccinated with a commercial modified-live virus combination vaccine or a sham vaccine at approximately 5 weeks of age and challenged with virulent type 2 BVDV 3.5 months after vaccination. Clinical signs of BVDV infection, development of viremia, and variation in WBC counts were recorded for 14 days after challenge exposure. RESULTS: Calves that received colostrum free of anti-BVDV antibodies and were vaccinated with the sham vaccine developed severe disease (4 of the 7 calves died or were euthanatized). Calves that received colostrum free of anti-BVDV antibodies and were vaccinated and calves that received colostrum with anti-BVDV antibodies and were vaccinated developed only mild or no clinical signs of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the modified-live virus vaccine induced a strong protective immune response in young calves, even when plasma concentrations of maternal antibody were high. In addition, all vaccinated calves were protected against viral shedding, whereas control calves vaccinated with the sham vaccine shed virus for an extended period of time.