Effects of a bovine herpesvirus-1 isolate on reproductive function in heifers: classification as a type-2 (infectious pustular vulvovaginitis) virus by restriction endonuclease analysis of viral DNA

A bovine herpesvirus-1 (BHV-1) isolate (FI) from an aborted fetus was used to infect 9 heifers at various stages of gestation. Two heifers were inoculated IV on postbreeding day (PBD) 1, 7, or 14, and 3 heifers were inoculated in the sixth month of pregnancy. Plasma progesterone assays were used to monitor corpus luteum function in heifers inoculated during early pregnancy. Low progesterone values and infertility were seen in the 2 heifers inoculated on PBD 1. Luteal function remained normal in heifers inoculated on PBD 7 or 14. These 4 heifers inoculated on PBD 7 or 14 carried their fetuses to term, and their calves were free of BHV-1 infection at birth. Three heifers inoculated during the sixth month of pregnancy also carried their fetuses to term. Two calves were born alive, and BHV-1 was not isolated from nasal swab samples of either calf; the third calf was stillborn. Virus was not isolated from the stillborn calf's tissues, but BHV-1 was isolated from the placenta. Lesions were not detected in several tissues examined by light microscopy, and BHV-1 antigen was not detected by immunohistochemical examination of paraffin sections. Restriction endonuclease analysis of viral DNA was used to compare the FI virus to other BHV-1 isolates (Colorado-1, Iowa, and K22). On the basis of restriction endonuclease analysis, the FI isolate should be classified as a type-2 (infectious pustular vulvovaginitis) virus, specifically subtype a.     

Early embryonic death in heifers after inoculation with bovine herpesvirus-1 and reactivation of latent virus in reproductive tissues

Thirteen crossbred heifers seronegative for bovine herpesvirus-1 (BHV-1) were bred naturally to a seronegative bull. Eight heifers were inoculated with BHV-1, IV, on postbreeding day (PBD) 7 or 14. Viremia was detected in heifers 1 through 7, and virus also was isolated from nasal and vaginal secretions of heifers 2, 3, 4, 6, and 7. The pregnancy status of all heifers was monitored from PBD 14 to PBD 35 by determining plasma progesterone concentrations at 1- to 3-day intervals. Decreased progesterone values indicated that pregnancy was not maintained in BHV-1-inoculated heifers 2, 3, 4, 6, 7, and 8. The postbreeding interestrual period of these 6 heifers was normal or only slightly longer than would be expected in the absence of conception. All 5 noninoculated heifers were pregnant on PBD 35. Three to 4 months after acute infection, all BHV-1 inoculated heifers were treated with dexamethasone for 5 days and were euthanatized. Nasal and vaginal swab specimens were tested daily during dexamethasone treatment for excreted BHV-1, and reproductive tissues and adrenal glands were collected at necropsy for virologic tests and histopathologic examination. Virus reactivation was demonstrated in heifers 2 through 8. The BHV-1 isolations were made from adrenal glands of heifers 2, 3, 5, 6, 7, and 8, vaginal swab specimens of heifers 2, 3, 4, 6, and 7, and nasal swab specimens of heifers 2, 3, and 6. Only heifer 3 had virus in reproductive tissues; these isolations were made from ovary, infundibulum, and uterine tube, but not from endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimentally induced infectious bovine rhinotracheitis virus infection during early pregnancy: effect on the bovine corpus luteum and conceptus

Pairs of heifers were inoculated IV with infectious bovine rhinotracheitis virus on postbreeding days (PBD) 7, 14, 21, or 28, and were euthanatized 13 to 15 days after inoculation. Reproductive tracts were examined for cytopathologic changes (light microscopy), virus (cell culture), and viral antigen (immunohistochemical evaluation). Heifers inoculated on PBD 7 or 14 had mild oophoritis characterized by foci of necrosis and mononuclear cell accumulations in the corpus luteum. Most of these heifers also had a few necrotic follicles in at least one ovary. Heifers inoculated on PBD 21 or 28 did not have corpus luteum lesions, but necrotic follicles were numerous in both ovaries. Viral antigen was observed in all ovarian lesions, and infectious virus was isolated from a few of the affected tissues. The uteri of all heifers inoculated on PBD 21 or 28 and 1 heifer inoculated on PBD 7 contained normal-appearing concepti. The uterus of the other PBD 7 heifer contained a degenerating conceptus that was infected with infectious bovine rhinotracheitis virus, as determined by viral isolation, immunohistochemical evaluation, and electron microscopy. Heifers inoculated on PBD 14 were not pregnant at necropsy, but histologic evidence was found that the postbreeding estrous cycle had been longer than normal, indicating that early embryonic death had occurred.     

Effect of primary and recurrent infections bovine rhinotracheitis virus infection on the bovine ovary

Six heifers were inoculated IV at estrus with the Iowa or Colorado isolates of infectious bovine rhinotracheitis virus (IBRV). Subsequent measurements of plasma progesterone indicated that corpus luteum function was depressed in all heifers. In the 1st estrous cycle after inoculation, progesterone values did not exceed 2 ng/ml in 3 heifers given the Iowa isolate. Although maximal progesterone values were greater than or equal to 2 ng/ml in 3 heifers given the Colorado isolate, values were lower than those in later cycles. Five heifers had maximal diestrual progesterone values greater than or equal to 5 ng/ml within 5 weeks after inoculation, but in the 6th heifer, this amount of progesterone was not present until 8 weeks after inoculation. Three to 5 months after inoculation, all heifers were given 5 daily injections of dexamethasone, 2 heifers each during metestrus, diestrus, or proestrus. Subsequent recrudescence of IBRV was demonstrated in all heifers by the isolation of virus from vaginal or nasal swab samples. The heifers were killed 10 to 17 days after initiation of dexamethasone treatment and their reproductive organs were examined for lesions and IBRV. Lesions were not seen, and IBRV was isolated only from the corpus luteum of a heifer given dexamethasone during diestrus.     

Ovarian lesions induced in heifers by intravenous inoculation with modified-live infectious bovine rhinotracheitis virus on the day after breeding

Four commercially available vaccine strains of modified-live infectious bovine rhinotracheitis virus were passaged once in embryonic bovine kidney cells. Heifers were inoculated IV on the day after breeding with 5.0 ml of nondiluted cell culture fluid of each of the 4 strains. Virus was reisolated from nasal swabs and blood collected during the week after inoculation. The heifers were killed 9 to 14 days after inoculation. Mild-to-marked inflammatory and necrotic lesions were seen in the corpora lutea and ovaries of the heifers. The lesions were similar to, and almost as severe as, those resulting from the inoculation of virulent strains of infectious bovine rhinotracheitis virus. Adrenal lesions were also found in all heifers examined. Virus was reisolated from the ovaries of only 4 of the 8 heifers. However, virus was confirmed in the ovaries of all 8 heifers, using immunofluorescent or ultrastructural studies. Heifers with severe luteal damage had abnormally low plasma progesterone concentrations.     

Association between route of inoculation with infectious bovine rhinotracheitis virus and site of recrudescence after dexamethasone treatment

Four calves latently infected with infectious bovine rhinotracheitis virus (IBRV) were used to compare the ease of isolation of virus from neuronal ganglia and from mucosal surfaces. Two calves were slaughtered, and neuronal ganglia (cranial cervical, trigeminal, and 3rd and 4th sacral) were cocultivated on bovine fetal kidney cells. Virus was not isolated. Two calves given dexamethasone for 4 days were slaughtered on the 5th day. Virus was not isolated from cocultivated or macerated neuronal ganglia, but virus was isolated from nasal secretions taken from both calves on the day of slaughter. Eleven calves were inoculated with IBRV via different routes and were treated with dexamethasone 3 to 4 months after inoculation. virus was isolated from the nasal cavities, but not the vaginas of 6 heifers inoculated intranasally, and was isolated from the vaginas, but not the nasal cavities of 2 heifers inoculated intravaginally. Of 3 calves inoculated IV, virus was isolated from the nasal cavities of 3, from the oropharynxes of 2, and from the prepuce of 1.     

Ovarian lesions in heifers exposed to infectious bovine rhinotracheitis virus by non-genital routes on the day after breeding

Twelve heifers were exposed to either a Colorado infectious bovine rhinotracheitis (IBR) virus isolate or an Iowa IBR isolate obtained from a bovine respiratory disease outbreak. All inoculations were made on the day after the heifers had been in estrus and bred by an IBR virus-negative bull. Pairs of heifers were inoculated with each virus isolate intravenously, intramuscularly or exposed by aerosol. The heifers were killed 11-15 days after inoculation and their reproductive tracts and ovaries subjected to virological and pathological study. Virus was isolated from the ovaries of all 4 heifers inoculated intravenously and from 3 of the 4 heifers inoculated intramuscularly, but not from the ovaries of heifers exposed by aerosol. Virus isolations and lesions were, with only 1 exception, confined to the ovary containing the corpus luteum. In ovaries from which IBR virus was isolated, lesions in the corpus luteum ranged from focal necrosis and infiltration of mononuclear cells to diffuse hemorrhage and necrosis. Most of these ovaries also had necrotic follicles and a diffuse mononuclear cell accumulation in the stroma. Lesions were not found in ovaries from which IBR virus was not isolated. It was concluded that lesions are readily induced in the ovaries of post-estrus heifers as a result of hematogenous spread of IBR virus and suggest that the differences in lesion development observed with the 3 routes are related to whether or not a viremia occurred.     

Necrotic oophoritis in heifers vaccinated intravenously with infectious bovine rhinotracheitis virus vaccine during estrus

Twenty-two Hereford heifers were injected IM with prostaglandin F2 alpha a, 11 days apart to synchronize estrous cycles. Twelve of 14 heifers that had signs of estrus were inoculated IV with 1 of 3 modified-live infectious bovine rhinotracheitis virus vaccines, and 2 were assigned to a nonvaccinated control group. Also, 6 of the 8 anestrous heifers were inoculated IV with 1 of the 3 vaccines on the fourth day after the last prostaglandin injection and the other 2 were assigned to the nonvaccinated group. Vaccine virus was isolated from the blood and nasal and vaginal secretions from the vaccinated heifers on postvaccination days 4, 7, and 9. On postvaccination day 9, all heifers were ovariectomized and ovarian tissues were processed for virus isolation and histologic examination. Vaccine virus was isolation and histologic examination. Vaccine virus was isolated from ovarian tissues of some heifers in each of the vaccine groups. Necrotic oophoritis characterized by multifocal areas of ovarian tissue necrosis, hemorrhage, and mononuclear lymphocytic infiltration was observed. The corpora lutea and surrounding ovarian tissues taken from vaccinated heifers in each group had varying amounts of necrotic and inflammatory change, but the changes appeared to be more severe in 1 group than in the other 2. Virus also was isolated from 2 of the controls; these heifers apparently became infected with vaccine virus that had been excreted from the vaccinated animals.     

Determination of ability of a thymidine kinase-negative deletion mutant of bovine herpesvirus-1 to cause abortion in cattle.

The Cooper isolate of bovine herpesvirus-1, which causes abortion in cattle, was used to construct a thymidine kinase-negative (TK-) deletion mutant virus. Twelve heifers were inoculated IV at 25 to 29 weeks of pregnancy with either TK- or thymidine kinase-positive (TK+) Cooper virus. All heifers developed fevers of 1 to 2 C during the first week after inoculation. Temperatures of TK+ inoculates were slightly higher and remained above normal a few days longer than in TK- inoculates. Viremia was detected in 5 of 6 TK+ inoculates and in all 6 TK- inoculates. More virus isolations were made from nasal and vaginal swab specimens of TK+ inoculates than from swab specimens of TK- inoculates. All heifers developed virus neutralizing antibody within 14 days after inoculation and antibody titers were similar between the 2 groups. None of the TK- inoculated heifers aborted and their calves did not have neutralizing antibody at birth. Abortion occurred in 5 of 6 heifers given TK+ virus. All aborted fetuses were infected with bovine herpesvirus-1, as demonstrated by virus isolation or detection of viral antigen in fetal tissues. These results indicate that inactivation of the TK gene reduces abortifacient activity of bovine herpesvirus-1.     

Effects of prostaglandin F2 alpha on degranulation of bovine luteal cells on days 4 and 12 of the estrous cycle

Corpora lutea were collected from 18 beef heifers on day 4 or 12 of the estrous cycle, 1 hour after prostaglandin (PG) F2 alpha or saline (control) treatment. Five heifers also were treated with PGF2 alpha on day 4, but their corpora lutea were not collected until day 12. The relative percentage of cytoplasm occupied by granules decreased only in large luteal cells (LLC) in heifers given PGF2 alpha on day 12, compared with the percentage in controls. Small luteal cells (SLC) were not as affected. The luteal concentration of progesterone was similarly decreased only in heifers given PGF2 alpha on day 12. Treatment of heifers with PGF2 alpha on day 4 had no marked effect on progesterone values or on the relative percentage of cytoplasm occupied by granules in LLC or SLC. Seemingly, LLC were more responsive to PGF2 alpha than were SLC, and PGF2 alpha treatment of beef heifers at day 4 did not markedly impair luteal function.     

Influence of epidermal growth factor on growth of bovine mammary tissue in athymic nude mice

Bovine mammary tissue obtained from midpregnant Holstein heifers by surgical biopsy was transplanted subcutaneously to ovariectomized athymic nude mice (n = 5 heifers). After 3 weeks recovery, mice were either sham operated or sialoadenectomized (submandibular salivary glands removed). After an additional week, mice were injected with saline or 17 beta-estradiol + progesterone (1 microgram + 1 mg/day) for 2 days. In addition, half of the sialoadenectomized mice were injected with epidermal growth factor (5 micrograms/day). Grafted tissue was removed and rate of deoxyribonucleic acid (DNA) synthesis estimated by incorporation of 3H thymidine. Estradiol + progesterone increased the incorporation of 3H thymidine from 77 +/- 20 dpm/micrograms DNA to 472 +/- 53 dpm/micrograms DNA. In sialoadenectomized mice, DNA synthesis was increased from 88 +/- 16 dpm/micrograms DNA (saline treated) to 360 +/- 29 dpm/micrograms DNA (estradiol + progesterone treated). In sialoadenectomized mice treated with epidermal growth factor, DNA synthesis in estradiol + progesterone treated mice was 529 +/- 36 dpm/micrograms DNA, compared to 112 +/- 30 dpm/micrograms DNA in sialoadenectomized mice treated with epidermal growth factor. These data indicate that sialoadenectomy of athymic nude mice decreased the ability of transplanted bovine mammary tissue to increase DNA synthesis in response to estradiol and progesterone. This inhibition was removed by epidermal growth factor treatment. These data suggest a physiological role of epidermal growth factor in regulating development and hormone responsiveness of bovine mammary tissue.     

Evaluation of the efficacy of a modified-live combination vaccine against bovine viral diarrhea virus types 1 and 2 challenge exposures in a one-year duration-of-immunity fetal protection study

This study demonstrated that the modified-live bovine viral diarrhea virus (BVDV) type 1 and 2 fractions of a multivalent vaccine protected pregnant heifers and their fetuses against virulent BVDV types 1 and 2 challenge exposures at 370 days after vaccination. All BVDV vaccinated heifers inoculated with either BVDV type 1 or 2 at approximately 62 to 94 days of gestation delivered fetuses or calves that were negative for BVDV by ear-notch immunohistochemistry and virus isolation and serum neutralization on a prenursing serum sample. In comparison, eight of nine and 10 of 10 fetuses or calves from non-BVDV-vaccinated heifers were considered persistently infected following exposure to BVDV type 1 and type 2, respectively.     

Efficacy of bovine herpesvirus-1 inactivated vaccine against abortion and stillbirth in pregnant heifers

OBJECTIVE: To evaluate the efficacy of an inactivated bovine herpesvirus-1 (BHV-1) vaccine to protect against BHV-1 challenge-induced abortion and stillbirth. DESIGN: Prospective study. ANIMALS: 35 beef heifers. PROCEDURES: Before breeding, heifers were vaccinated with a commercially available BHV-1 inactivated vaccine SC or IM. The estrous cycle was then synchronized, and heifers were artificially inseminated 30 to 60 days after vaccination. Heifers (n = 21) were challenge inoculated IV at approximately 180 days of gestation with virulent BHV-1. Fourteen control heifers were not vaccinated. Clinical signs of BHV-1 infection were monitored for 10 days following challenge; serologic status and occurrence of abortion or stillbirth were evaluated until time of calving. RESULTS: 18 of 21 (85.7%) heifers that received vaccine were protected from abortion following challenge, whereas all 14 control heifers aborted. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that an inactivated BHV-1 vaccine can protect against abortion resulting from a substantial challenge infection, with efficacy similar to that of modified-live BHV-1 vaccines.     

Comparison of humoral immune responses in dairy heifers vaccinated with 3 different commercial vaccines against bovine viral diarrhea virus and bovine herpesvirus-1

A randomized clinical trial was conducted to compare the humoral immune response to 3 different commercial vaccines in dairy heifers housed in 3 different dairy farms in Quebec. All heifers were seronegative to type 1 bovine viral diarrhea virus (BVDV) (Singer strain), type 2 BVDV (NVSL 125c strain), and bovine herpesvirus-1 (BHV-1) at the beginning of the trial. In addition, control heifers in group 1 remained seronegative to the 2 viruses till the end of the trial. Significant differences in humoral immune responses occurred among the 3 commercial vaccines at 4 weeks and 6 months following vaccination. The vaccine in group 2 elicited higher mean antibody titers and seroconversion rates to both type 1 and type 2 BVDV than that in groups 3 or 4. Vaccines in groups 2 and 3 induced higher mean antibody titers to BHV-1 than did the vaccine in group 4.     

Plasma progesterone concentration in beef heifers receiving exogenous glucose, insulin, or bovine somatotropin

Three experiments were conducted to evaluate plasma concentrations of glucose, insulin, IGF-I, and progesterone (P4) in pubertal beef heifers receiving exogenous glucose, insulin, or sometribove zinc. All heifers used had no luteal P4 synthesis but received a controlled internal drug-releasing device containing 1.38 g of P4 to estimate treatment effects on hepatic P4 degradation. In Exp. 1, 8 pubertal, nulliparous Angus × Hereford heifers (initial BW = 442 ± 14 kg; initial age = 656 ± 7 d) were randomly assigned to receive, in a crossover design containing 2 periods of 10 h, intravenous (i.v.) infusions (10 mL) of insulin (1 μg/kg of BW; INS) or saline (0.9%; SAL). Treatments were administered via jugular venipuncture in 7 applications (0.15 μg insulin/kg BW per application) 45 min apart (from 0 to 270 min). Blood samples were collected immediately before each infusion as well as at -120, -60, 330, 390, and 450 min relative to the first infusion. Heifers receiving INS had greater (P < 0.01) plasma insulin, reduced (P ≤ 0.04) plasma glucose and IGF-I, and similar (P = 0.62) plasma P4 concentrations compared with SAL heifers. In Exp. 2, the same heifers were assigned to receive, in a similar experimental design as Exp. 1, i.v. infusions (10 mL) of 1) insulin (1 μg/kg BW) and glucose (0.5 g/kg BW; INS+G) or 2) SAL. Heifers receiving INS+G had greater (P ≤ 0.02) plasma insulin, glucose, and P4 but reduced (P = 0.01) plasma IGF-I concentrations compared with SAL heifers. In Exp. 3, the same heifers were assigned to receive, in a crossover design containing 2 periods of 14 d, subcutaneous (s.c.) injections of 1) 250 mg of sometribove zinc (BST) or 2) SAL. Blood samples were collected 3 h apart (0900, 1200, 1500, and 1800 h) from heifers on d 6, 8, and 10 relative to treatment administration (d 1). Heifers receiving BST had greater (P < 0.01) plasma glucose and IGF-I and similar (P ≥ 0.67) plasma insulin and P4 concentrations compared with SAL heifers. Results from this series of experiments suggested that concurrent increases in glucose and insulin are required to reduce hepatic catabolism and increase plasma concentrations of P4 in bovine females.     

Pathogenetic studies of infection of the bovine fetus with bovine viral diarrhea virus. II. Ocular lesions.

Twenty-three susceptible pregnant heifers were inoculated with bovine viral diarrhea virus at 150 +/- 1 days of gestation. Seven additional heifers were inoculated between 65 and 115 days of gestation. Acute ocular lesions were seen in fetuses taken 17-21 days after inoculation of the dams at 150 days. By the fourth week, the acute lesions were beginning to resolve, and in newborn animals focal to total retinal atrophy was seen. The acute lesions were characterized by a mild to moderate retinitis that resulted in various degrees of destruction of the different layers, mononuclear cuffing of inner retinal vessels, proliferation of pigment epithelium, and choroiditis. Residually there was an absence of cellular elements in the atrophied areas of the retina, frequently a loss of layering and various numbers of pigment-containing cells. Moderately severe acute inflammation was seen in the retina of the fetus taken at 22 days after inoculation of its dam at 95 days. Ocular lesions did not occur in the other fetuses taken from heifers inoculated at earlier stages of gestation.     

Papillomatosis of the bovine teat (mammary papilla)

A 4th of 667 cattle examined at a Wisconsin abattoir had teat papillomas. Excised teat papillomas were sorted by gross morphologic characteristics into 3 groups: (i) atypical filiform, (ii) atypical flat, and (iii) typical fibropapilloma. Bovine papilloma virus capsid antigen was detected in thin-section slides of the 3 groups of teat papillomas by peroxidase-antiperoxidase assay. The bovine papilloma virus involved with the atypical papillomas could not be characterized by molecular hybridization, because enough pure virus could not be harvested. Homogenates of the 3 groups of teat papillomas were inoculated on 2 ponies and 4 calves. Typical fibropapillomas were produced on the 4 calves, and fibromas, on the 2 ponies. Atypical papillomas were produced only in 2 heifers.     

Demonstration of infectious bovine rhinotracheitis virus antigen in paraffin sections

Nine pregnant heifers were inoculated intravenously with infectious bovine rhinotracheitis virus (IBRV) in the sixth month of pregnancy. Tissues were collected from the fetus of a heifer killed 13 days postinoculation (PI), from fetuses of 6 heifers that aborted 16-27 days PI, and from mummified fetuses of 2 heifers that aborted 53 and 85 days PI, respectively. Control tissues were obtained from the fetus of a non-inoculated heifer that was killed in the seventh month of gestation. Tissues were fixed in 10% formalin, embedded in paraffin, and examined for viral antigen by immunohistochemistry, using biotinylated second antibody and alkaline phosphatase-labeled avidin-biotin complex. Antigen was detected in at least 1 tissue from the fetus of each inoculated heifer. Positive tissues included lung, liver, spleen, kidney, adrenal, and placenta. In several fetuses, antigen was identified in tissues from which virus was not isolated in cell culture. This appeared to occur when tissues had only a few small foci of infection or when tissues were severely autolyzed. The observation of viral antigen in tissues from mummified fetuses indicates that this technique may be useful in diagnostic laboratories to detect IBRV infection in tissues that are not suitable for virus isolation or for examination by the cryostat tissue section-fluorescent antibody technique.     

Inhibition of bovine luteal function by indomethacin

Experiments were conducted to determine the effects of infusing indomethacin, a prostaglandin synthetase inhibitor, into the uterine lumen on the development and function of the bovine corpus luteum in the presence and absence of concurrently administered oxytocin. Each treatment was given twice daily on d 4, 5 and 6 of the estrous cycle. Treatments (six heifers/group) and resulting estrous cycle lengths were as follows: (1) untreated controls, 20.6 +/- .4 d; (2) .2 M phosphate buffer vehicle infused into the uterine lumen, 21.0 +/- .6 d; (3) 40 mg indomethacin infused into the body of the uterus, 16.5 +/- 1.0 d; (4) 150 USP units oxytocin injected sc, 10.0 +/- 1.2 d and (5) a combination of oxytocin and indomethacin as in treatments 3 and 4, 14.1 +/- 1.3 d. Plasma concentrations of progesterone were lower (P less than .05) in each treatment group from d 7 onward, when compared with untreated and vehicle-treated controls. Indomethacin alone effectively inhibited the development and function of the corpus luteum, and was without effect on oxytocin-induced inhibition of luteal function. In summary, it appears that a prostaglandin of either uterine or ovarian origin, or both, is required for the normal development and function of the bovine corpus luteum.     

Protective effects against abortion and fetal infection following exposure to bovine viral diarrhea virus and bovine herpesvirus 1 during pregnancy in beef heifers that received two doses of a multivalent modified-live virus vaccine prior to breeding

Objective-To determine whether administration of 2 doses of a multivalent, modified-live virus vaccine prior to breeding of heifers would provide protection against abortion and fetal infection following exposure of pregnant heifers to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) and cattle with acute bovine herpesvirus 1 (BHV1) infection. Design-Randomized controlled clinical trial. Animals-33 crossbred beef heifers, 3 steers, 6 bulls, and 25 calves. Procedures-20 of 22 vaccinated and 10 of 11 unvaccinated heifers became pregnant and were commingled with 3 steers PI with BVDV type 1a, 1b, or 2 for 56 days beginning 102 days after the second vaccination (administered 30 days after the first vaccination). Eighty days following removal of BVDV-PI steers, heifers were commingled with 3 bulls with acute BHV1 infection for 14 days. Results-After BVDV exposure, 1 fetus (not evaluated) was aborted by a vaccinated heifer; BVDV was detected in 0 of 19 calves from vaccinated heifers and in all 4 fetuses (aborted after BHV1 exposure) and 6 calves from unvaccinated heifers. Bovine herpesvirus 1 was not detected in any fetus or calf and associated fetal membranes in either treatment group. Vaccinated heifers had longer gestation periods and calves with greater birth weights, weaning weights, average daily gains, and market value at weaning, compared with those for calves born to unvaccinated heifers. Conclusions and Clinical Relevance-Prebreeding administration of a modified-live virus vaccine to heifers resulted in fewer abortions and BVDV-PI offspring and improved growth and increased market value of weaned calves.