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.     

Active and Passive Immunity to Bovine Viral Respiratory Diseases in Beef Calves After Shipment

Fifteen steers were vaccinated after shipment with a modified live virus vaccine containing infectious bovine rhinotracheitis (IBR), bovine virus diarrhea (BVD), and bovine myxovirus parainfluenza-3 (PI3), and 16 unvaccinated steers were kept as controls. Geometric mean titers one month after vaccination were highest to BVD, followed by PI3 and IBR. Weight gains were higher during 30 days after vaccination in the controls. One case of acute respiratory disease developed in one vaccinated calf. Revaccination 79 days after the first dose increased antibody to PI3 and BVD virus but not IBR. In a second trial, no clinical respiratory disease developed after shipment of 13 heifers that received an antibacterial-antiviral antiserum or in the 12 controls. Weight gains 30 days after shipment were identical in both groups.     

Effect of age at the time of vaccination on antibody titers and feedlot performance in beef calves

OBJECTIVE: To compare antibody responses, feedlot morbidity and mortality rates, feedlot performance, and carcass value for calves vaccinated with 1 of 2 vaccination strategies and for unvaccinated control calves. DESIGN: Randomized controlled clinical trial. ANIMALS: 451 beef steers and heifers. PROCEDURES: Calves were vaccinated with a modified-live infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus vaccine and Mannheimia haemolytica and Pasteurella multocida bacterin-toxoid at approximately 67 and 190 days of age (group 1; n = 151) or at approximately 167 and 190 days of age (group 2; 150) or were not vaccinated (control; 150). Serum antibody titers were measured at approximately 2, 67, 167, 190, and 232 days of age. Morbidity and mortality rates, feedlot performance, and carcass value were recorded for 361 calves shipped to feedlots. RESULTS: Percentages of calves seroconverting to IBRV, BVDV1, and BVDV2 were significantly higher for groups 1 and 2 than for the control group. Mean treatment costs were significantly lower for vaccinated than for control calves, and mean mortality rate was significantly higher for control calves than for group 1 calves. Feedlot performance and carcass value did not vary significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that vaccination of beef calves with a 5-antigen modified-live virus vaccine at 67 and 190 days of age was as effective in terms of immunologic responses as was vaccination at 167 and 190 days of age.     

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.     

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.     

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.     

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.     

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.     

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.     

Evaluation of a quadrivalent inactivated vaccine for the protection of cattle against diseases due to common viral infections

Efficacy of an inactivated quadrivalent vaccine containing infectious bovine rhinotracheitis (IBR) virus, parainfluenza type 3 (PI3) virus, bovine virus diarrhoea virus (BVDV) and bovine respiratory syncytial virus (BRSV) was assessed in naive bovine calves to evaluate short-term (4-18 weeks) and long-term (24-38 weeks) protection following the basic intramuscular vaccination regime of 2 inoculations a month apart. Vaccination was staggered between the long-term and the short-term groups by about 5 months so that both groups, along with a matched group of 6 unvaccinated (control) calves, could be challenged at the same time. Sequential challenges at intervals of 3-8 weeks were done in the order: IBR virus (intranasally, IN), PI3 virus (IN and intratracheally, IT), pestiviruses (IN) and BRSV (IN and IT). The IBR virus challenge produced febrile rhinotracheitis (FRT) in control calves but both the severity and the duration of FRT was significantly reduced in both vaccinated groups. The amount and the duration of IBR virus shed by the vaccinated groups was significantly reduced compared to the control group. Although PI3 virus, pooled pestivirus and BRSV challenges did not result in a noteworthy disease, challenge virus shedding (amount and duration) from the upper (all 3 viruses) and the lower (BRSV) respiratory tracts was significantly reduced in vaccinated groups. After pestivirus challenge, sera and leukocytes from all control calves were infectious for 6-9 days whereas virus was recovered only from leukocytes in vaccinated calves and only for 1.6-2.7 days. Thus a standard course of the quadrivalent vaccine afforded a significant protection against IBR virus, PI3 virus, BVDV and BRSV for at least 6 months.     

Fetal protection following exposure to calves persistently infected with bovine viral diarrhea virus type 2 sixteen months after primary vaccination of the dams

This study demonstrated that the bovine viral diarrhea virus (BVDV; types 1 and 2) fractions of a multivalent vaccine protected pregnant heifers and their fetuses at 149 to 217 days of gestation against exposure to calves persistently infected with BVDV type 2a. Eighty percent (eight of 10) of the control heifers were viremic at least 1 day following challenge, whereas all (20 of 20) BVDV-vaccinated heifers were virus isolation-negative on all postchallenge assessment days. Ninety percent (nine of 10) of the calves born to control heifers but only 5% (one of 20) of calves born to BVDV-vaccinated heifers seroconverted to BVDV type 2 before ingesting colostrum. One calf born to a control heifer was persistently infected. No calves from BVDV-vaccinated heifers were persistently infected.     

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 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.     

Serologic evaluation of five unvaccinated heifers to detect herds that have cattle persistently infected with bovine viral diarrhea virus

OBJECTIVE: To determine whether serologic evaluation of 5 unvaccinated 6- to 12-month-old heifers is a valid method for identifying herds that contain cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV). ANIMALS: 14 dairy herds with a history of BVDV infection, with health problems consistent with BVDV infection, or at risk for contracting BVDV infection. PROCEDURE: 5 unvaccinated 6- to 12-month-old heifers were randomly selected from each herd. Neutralizing antibody titers for type-I and -II BVDV were determined. A herd was classified as likely to contain PI cattle when at least 3/5 heifers had antibody titers > or = 128. Virus isolation was performed on all cattle to identify PI cattle. Genotype of isolated viruses was determined by nested multiplex polymerase chain reaction. RESULTS: 6 of 14 herds contained PI cattle. Sensitivity and specificity of serologic evaluation of 5 heifers for identifying these herds were 66 and 100%, respectively. In herds that contained PI cattle, the predominant BVDV titer in the tested heifers corresponded to the genotype of the isolated virus. CONCLUSIONS AND CLINICAL RELEVANCE: Serologic evaluation of unvaccinated 6- to 12- month-old heifers is an accurate method for identifying herds containing PI cattle. Both type-I and -II BVDV antibody titers should be determined to prevent herd misclassification. The genotype of BVDV found in PI cattle can be predicted by the predominant neutralizing antibody titers found in tested heifers. Serologic evaluation of 5 unvaccinated heifers can be used to determine whether a herd is likely to contain PI cattle.     

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.     

The associations of viral and mycoplasmal antibody titers with respiratory disease and weight gain in feedlot calves

Blood samples from 32 groups of calves (n = 700) were taken on arrival and after 28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and 21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and M. bovis, plus data on bovine corona virus (BCV) from a previous study were investigated for their association with the risk of bovine respiratory disease (BRD), and with 28-day weight change, both before and after controlling for titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M. bovis was infrequent, and although exposure to PIV-3 was more common, none of these agents had important associations with BRD. Higher titers to BVDV, BRSV, and BCV on arrival were associated with reduced risks of BRD and increased weight gains. However, there was some variation in these relationships and higher arrival titers to BVDV and BRSV in a subset of the calves were associated with increased risks of BRD. Titer increases to BVDV were associated with a higher risk of BRD and lower weight gains. Titer increases to BRSV were not usually associated with the occurrence of BRD, but titer increases to BRSV in a subset of calves that were vaccinated against BRSV, on arrival, were associated with an elevated risk of BRD. Of all the agents studied, BVDV had the most consistent associations with elevated risk of BRD and lower weight gains. Higher BRSV arrival titers were related to lower risk of BRD and higher weight gains; in some instances titer increases to BRSV were associated with higher BRD risk. Higher titers to BCV on arrival were related to reduced risks of BRD. Practical ways of adequately preventing the negative effects of these agents are still needed.     

Onset of protection from experimental infection with type 2 bovine viral diarrhea virus following vaccination with a modified-live vaccine

The onset of protection after the administration of a modified-live bovine viral diarrhea virus (BVDV) vaccine was determined. Protection was determined following experimental infection with a virulent type-2 BVDV (strain 1373) in cattle vaccinated 3, 5, or 7 days before BVDV infection. Protection, as measured by reduced virus shedding, lack of leukopenia, reduction in viremia, and reduced mortality, was present as early as 3 days after vaccination with a single dose of modified-live BVDV vaccine. Complete protection was obtained in cattle vaccinated 5 or 7 days before BVDV experimental infection.     

Effects of supplemental chromium on antibody responses of newly weaned feedlot calves to immunization with infectious bovine rhinotracheitis and parainfluenza 3 virus.

The objective of this study was to determine the effect of supplemental dietary chromium (Cr) on antibody responses of feedlot calves. Fifty-five newly weaned calves were divided into two groups, 28 that received supplemental Cr and 27 that did not, and were immunized with a commercial vaccine against bovine infectious rhinotracheitis virus (IBR) and bovine parainfluenza virus type 3(PI-3). Sera harvested from blood sampled preimmunization, and at days 14 and 28 postimmunization (PI), were assayed for anti-IBR and anti-PI-3 antibody titers. Individual calves were also scored as seroconverters if day 14 or 28 PI titers were > or = 3 times the value of the preimmunization titer. Thirty-five calves did not seroconvert to either antigen. Of 20 IBR seroconverters, 15 calves were from the Cr-supplemented group while only five calves were controls (p = 0.007). There was no treatment difference in the number of PI-3 seroconverters. Least squares analysis of actual antibody titers revealed that Cr supplementation increased the magnitude of the peak antibody response to the IBR (p = 0.003), but had no effect on anti-PI-3 antibody titers. These data confirmed and extended our previous observations that supplemental Cr can be immunomodulatory in cattle.