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.     

Fetal protection against bovine viral diarrhea virus types 1 and 2 after the use of a modified-live virus vaccine

The objective of this study was to demonstrate the efficacy of a modified-live virus (MLV) vaccine in protecting fetuses from infection with type 1 or type 2 Bovine viral diarrhea virus (BVDV) when pregnant heifers were challenged at approximately 170 d of gestation with noncytopathic field isolates. The 83 pregnant heifers had been bred naturally 4 wk after vaccination. Fetuses were collected 60 d after BVDV type 2 challenge, and newborn calves were collected before colostrum intake after BVDV type 1 challenge. Protection was determined by measuring the serum neutralizing (SN) antibody response in the fetus or calf and by virus isolation from thymus, lung, spleen, and kidney tissue samples. There was a measurable SN antibody response to BVDV in all the fetuses and calves of the control heifers, which had received a placebo vaccine. However, only 4 of 22 calves and 7 of the 28 fetuses of the MLV-vaccinated heifers demonstrated SN antibody after BVDV challenge. Type 1 BVDV was isolated from tissue samples of 5 of the 12 calves of control heifers and none of 22 calves of the MLV-vaccinated heifers challenged with type 1 BVDV. Type 2 BVDV was isolated from tissue samples of 17 of the 18 fetuses of the control heifers and 2 of the 28 fetuses of the MLV-vaccinated heifers challenged with type 2 BVDV. The results of this study demonstrate that the MLV vaccine reduces the fetal infection rate by at least 82% for BVDV type 1 and by 75% for BVDV type 2 when heifers are exposed to highly fetotrophic BVDV at 170 d of gestation.     

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.     

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.     

Protection against fetal infection with either bovine viral diarrhea virus type 1 or type 2 using a noncytopathic type 1 modified-live virus vaccine

Two bovine viral diarrhea virus (BVDV) fetal protection studies were done using a monovalent noncytopathic (NCP) BVDV vaccine containing type 1 BVDV. In study 1, thirty-two fetuses (23 vaccinates and nine controls) were recovered following fetal challenge with the type 1a BJ strain. Twenty of twenty-three fetuses from the vaccinates were negative for BVDV type 1 while all of the controls (nine of nine) were infected. In study 2, twenty-two animals (14 vaccinates and eight controls) were challenged with the type 2 PA131 strain. Thirteen of the fourteen fetuses from the vaccinates were negative for BVDV type 2 while all of the nonvaccinated controls (eight of eight) were infected. These results indicate the efficacy of a monovalent NCP BVDV vaccine in providing excellent protection against either BVDV type 1 or 2 fetal infection.     

Attenuation of a virulent type 2 bovine viral diarrhea virus

The purpose of this study was to produce an attenuated bovine viral diarrhea virus (BVDV) type 2 strain as a tool for identifying potential virulence markers in the BVDV2 genome. The attenuation of the virulent strain, BVDV2-24515, was accomplished by in vivo and in vitro passage. The strain was initially used to infect an elk (Cervus elaphus) [J. Wildl. Dis. 35 (1999) 671], re-isolated at 7 days post-inoculation from serum, and then subsequently passaged 56 times in cell culture. Two groups of calves were inoculated intranasally with either BVDV2-24515 or the putative attenuated virus, designated BVDV2-LATT. Calves inoculated with BVDV2-24515 had cumulative clinical scores which ranged from 6 to 53. Clinical signs in these calves consisted of anorexia, depression, dehydration, diarrhea (±bloody), and pneumonia. Several calves developed leukocytopenia, primarily a neutrocytopenia, and presented lesions of enteritis or pneumonia at necropsy. In contrast, cattle inoculated with BVDV2-LATT had cumulative clinical scores which ranged from 0 to 2. This was not significantly different from that of controls which received no virus (range: 0–1). Calves inoculated with BVDV2-LATT produced high neutralizing antibody titers against BVDV2. Thus, in addition to its potential use as a tool for identifying virulence markers, the attenuated virus is also worthy of further study as a candidate virus for inclusion in a modified-live vaccine.     

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.     

Efficacy of bovine viral diarrhea vaccine used in Japan against bovine viral diarrhea virus type 2 strain 890

Bovine viral diarrhea virus (BVDV) has been segregated into two genotypes, type 1 and type 2. To determine the efficacy of the commercially available bovine viral diarrhea type 1 vaccine used in Japan against BVDV type 2, calves were infected with BVDV type 2 strain 890 4 weeks after administration of the vaccine. The vaccinated calves did not develop any clinical signs and hematological changes such as observed in unvaccinated calves after the challenge. Furthermore, the challenge virus was not recovered from the vaccinated calves throughout the duration of the experiment, whereas it was recovered from all unvaccinated calves. The bovine viral diarrhea vaccine used in Japan is efficacious against infection with BVDV type 2 strain 890.     

Correlation between maternal serum antibodies and protection against bovine rotavirus diarrhea in calves

The correlation between maternal serum antibodies in beef calves at 2 days old and protection against diarrhea induced by natural bovine rotavirus (BRV) infection was examined. Virus neutralizing (VN) antibody titers against BRV in sera from calves that developed diarrhea by BRV infection within 14 days of age (BRV-diarrheal calves) were significantly lower than those from calves that had no diarrhea. In the BRV-diarrheal calves, a positive correlation was found between the VN antibody titers and age of the onset of diarrhea. There were negative correlations between the VN antibody titers and duration of the diarrhea, VN antibody titers and cumulative diarrhea scores, and the VN antibody titers and duration of virus shedding. These results suggest that the VN antibody titers against BRV in newborn calf serum could be an indicator of protection against BRV-induced diarrhea.     

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.     

Specificity of neutralizing and precipitating antibodies induced in healthy calves by monovalent modified-live bovine viral diarrhea virus vaccines

Serum was obtained at weekly intervals after vaccination of 6 healthy calves with either of 2 commercially available monovalent modified-live bovine viral diarrhea (BVD) virus vaccines. Detectable neutralizing antibodies to each of 10 cytopathic and 10 noncytopathic isolates of BVD virus were produced by 1 or more of the calves by 14 days after vaccination, but no calf produced detectable neutralizing antibodies to all 20 BVD viruses. At that time, precipitating antibodies against viral-induced polypeptides of approximately 115,000; 80,000; 56,000; 48,000; 39,000; and 25,000 daltons were detected in sera from some calves. Also at that time, specificity of the antibodies for polypeptides of certain viruses was detected. At 21 days after vaccination, each calf produced neutralizing antibodies to all 20 BVD viruses. At that time, precipitating antibodies to each of the aforementioned viral induced polypeptides were detected in serum from each calf. Precipitating antibodies to viral induced polypeptides of 61,000 and 37,000 daltons were detected in samples of sera obtained from some calves at 42 days after vaccination.     

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

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

Use of a modified-live vaccine to prevent persistent testicular infection with bovine viral diarrhea virus

A commercial vaccine containing modified-live bovine viral diarrhea virus (BVDV; types 1 and 2) was administered to one group of 22 peripubertal bulls 28 days before intranasal inoculation with a type 1 strain of BVDV. A second group of 23 peripubertal bulls did not receive the modified-live BVDV vaccine before intranasal inoculation. Ten of 23 unvaccinated bulls--but none of the vaccinated bulls--developed a persistent testicular infection as determined by immunohistochemistry and polymerase chain reaction. Results of this study indicate that administration of a modified-live vaccine containing BVDV can prevent persistent testicular infection if peripubertal bulls are vaccinated before viral exposure.     

Effect of maternal antibodies on induction and persistence of vaccine-induced immune responses against bovine viral diarrhea virus type II in young calves

OBJECTIVE: To determine the effect of maternally derived antibodies on induction of protective immune responses against bovine viral diarrhea virus (BVDV) type II in young calves vaccinated with a modified-live bovine viral diarrhea virus (BVDV) type I vaccine. DESIGN: Blinded controlled challenge study. ANIMALS: 24 neonatal Holstein and Holstein-cross calves that were deprived of maternal colostrum and fed pooled colostrum that contained a high concentration of (n = 6) or no (18) antibodies to BVDV. PROCEDURE: At 10 to 14 days of age, 6 seropositive and 6 seronegative calves were given a combination vaccine containing modified-live BVDV type I. All calves were kept in isolation for 4.5 months. Six calves of the remaining 12 untreated calves were vaccinated with the same combination vaccine at approximately 4 months of age. Three weeks later, all calves were challenged intranasally with a virulent BVDV type II. RESULTS: Seronegative unvaccinated calves and seropositive calves that were vaccinated at 2 weeks of age developed severe disease, and 4 calves in each of these groups required euthanasia. Seronegative calves that were vaccinated at 2 weeks or 4 months of age developed only mild or no clinical signs of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that a single dose of a modified-live BVDV type-I vaccine given at 10 to 14 days of age can protect susceptible young calves from virulent BVDV type II infection for at least 4 months, but high concentrations of BVDV-specific maternally derived antibodies can block the induction of the response.     

Virus neutralising antibodies against 22 bovine viral diarrhoea virus isolates in vaccinated calves.

Seven of nine colostrum deprived calves, free from bovine viral diarrhoea virus (BVDV), were vaccinated with a commercially available vaccine containing two inactivated strains of BVDV, an inactivated strain of bovine herpesvirus-1 and modified-live strains of bovine respiratory syncytial virus and para-influenza-3 virus. The two other calves were kept as controls. The virus neutralising (VN) antibodies induced by vaccination were tested against 22 antigenically diverse BVDV isolates, including reference strains and field isolates, both cytopathic and non-cytopathic, as well as genotypes I and II. The strains were isolated in Belgium, France, Germany, the United Kingdom and the USA. While there were variations in the VN titres of the individual calves against all the strains, serum from the seven animals neutralised 20 or more of the strains tested. From the results, it can be concluded that the vaccine can stimulate the production of VN antibodies capable of neutralising a wide range of European and American isolates of BVDV, including genotypes I and II.