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.     

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.     

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.     

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.     

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.     

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.     

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

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

Development of a fetal challenge method for the evaluation of bovine viral diarrhea virus vaccines

A method to evaluate the efficacy of bovine viral diarrhea virus (BVDV) vaccines using a multiple challenge model was investigated. Four pregnant heifers were challenged intranasally with a type I and type II isolate of BVDV at 75 days of gestation. At 60 days postinoculation, virus isolation and RT-PCR from blood and tissues of fetuses indicated that all fetus were persistently infected with both type I and type II isolates. Differing results of detection by PCR and virus isolation between the type I and type II isolates were obtained. These preliminary studies may indicate differences in the level of replication between type I and type II BVDV as well as predilected sites of replication in certain tissues.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Failure of foetal protection after vaccination against an experimental infection with bovine virus diarrhea virus

A protocol is described to measure the protection of the bovine fetus against an experimental bovine virus diarrhea virus (BVDV) infection after vaccination. Two inactivated experimental vaccines were applied twice with a 3 week interval. A mixture of three different Dutch field strains was used as challenge on mainly the 82nd day of gestation to vaccinated and unvaccinated control animals. The challenge was applied 5 months after completion of the two-fold vaccinations. All calves born from unvaccinated control animals were persistently infected. The calves born from dams vaccinated with the two different inactivated BVDV vaccines were persistently infected in 78 and 60%, 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.     

Transmission of Bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves

Bovine viral diarrhea virus (BVDV) persistently infected (PI) calves represent significant sources of infection to susceptible cattle. The objectives of this study were to determine if PI calves transmitted infection to vaccinated and unvaccinated calves, to determine if BVDV vaccine strains could be differentiated from the PI field strains by subtyping molecular techniques, and if there were different rates of recovery from peripheral blood leukocytes (PBL) versus serums for acutely infected calves. Calves PI with BVDV1b were placed in pens with nonvaccinated and vaccinated calves for 35 d. Peripheral blood leukocytes, serums, and nasal swabs were collected for viral isolation and serology. In addition, transmission of Bovine herpes virus 1 (BHV-1), Parainfluenza-3 virus (PI-3V), and Bovine respiratory syncytial virus (BRSV) was monitored during the 35 d observation period. Bovine viral diarrhea virus subtype 1b was transmitted to both vaccinated and nonvaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to PI calves. There was evidence of transmission by viral isolation from PBL, nasal swabs, or both, and seroconversions to BVDV1b. For the unvaccinated calves, 83.2% seroconverted to BVDV1b. The high level of transmission by PI calves is illustrated by seroconversion rates of nonvaccinated calves in individual pens: 70% to 100% seroconversion to the BVDV1b. Bovine viral diarrhea virus was isolated from 45 out of 202 calves in this study. These included BVDV1b in ranch and order buyer (OB) calves, plus BVDV strains identified as vaccinal strains that were in modified live virus (MLV) vaccines given to half the OB calves 3 d prior to the study. The BVDV1b isolates in exposed calves were detected between collection days 7 and 21 after exposure to PI calves. Bovine viral diarrhea virus was recovered more frequently from PBL than serum in acutely infected calves. Bovine viral diarrhea virus was also isolated from the lungs of 2 of 7 calves that were dying with pulmonary lesions. Two of the calves dying with pneumonic lesions in the study had been BVDV1b viremic prior to death. Bovine viral diarrhea virus 1b was isolated from both calves that received the killed or MLV vaccines. There were cytopathic (CP) strains isolated from MLV vaccinated calves during the same time frame as the BVDV1b isolations. These viruses were typed by polymerase chain reaction (PCR) and genetic sequencing, and most CP were confirmed as vaccinal origin. A BVDV2 NCP strain was found in only 1 OB calf, on multiple collections, and the calf seroconverted to BVDV2. This virus was not identical to the BVDV2 CP 296 vaccine strain. The use of subtyping is required to differentiate vaccinal strains from the field strains. This study detected 2 different vaccine strains, the BVDV1b in PI calves and infected contact calves, and a heterologous BVDV2 subtype brought in as an acutely infected calf. The MLV vaccination, with BVDV1a and BVDV2 components, administered 3 d prior to exposure to PI calves did not protect 100% against BVDV1b viremias or nasal shedding. There were other agents associated with the bovine respiratory disease signs and lesions in this study including Mannheimia haemolytica, Mycoplasma spp., PI-3V, BRSV, and BHV-1.     

A new inactivated BVDV genotype I and II vaccine. An immunisation and challenge study with BVDV genotype I

An inactivated vaccine containing BVDV I and II strains (PT810; BVDV I, and 890; BVDV II) and using different adjuvants and antigen dosages was tested in a cattle challenge model. Groups of six healthy, seronegative cattle were vaccinated twice with a low dose (10(6.6) TCID(50) PT810 and 10(7.2) TCID(50) 890) vaccine with the adjuvant Bay R1005 or a high dose (10(7.8) TCID(50) PT810 and 10(8. 2) TCID(50) 890) vaccine with two different adjuvants (Bay R1005 or Polygen). Thirty-eight days after the second vaccination, immunised animals (n=18) and non-vaccinated control animals (n=3) were challenged intranasally with 10(6) TCID(50) BVDV strain PT810. For a period of 16 days, virus was isolated from blood leukocytes and nasal swabs, and neutralising antibody titres were determined.The induction of antibodies following immunisation was strongly dependent on the antigen dosage in the vaccine. The high dose formulation induced high serum neutralising antibody titres against both genotypes of up to 32000 after the second immunisation. Animals with neutralising antibody titres >512 (n=14) did not show any marked leukopenia after challenge and only very little or no virus could be isolated from blood leukocytes and/or nasal swabs when compared to control cattle. Furthermore, some of these animals did not show any boost of neutralising or even NS3-specific antibodies, which renders viral replication unlikely and thus would prevent infection of the fetus. Both adjuvants (Bay R1005 or Polygen) were similarly efficient and induced nearly identical antibody responses. In contrast, four of the six low dosage vaccinates had a marked leukopenia and viraemia as well as detectable nasal virus shedding for several days.We conclude that the selected strains and the system of vaccine preparation with high BVDV antigen dosages and highly efficient new adjuvants provide an effective means of protection against BVDV I infections. Investigations to demonstrate the protection against BVDV II infections, the duration of immunity and the ability of fetal protection by using the high dose vaccine in a fetal challenge model will follow.     

Development of a classical swine fever subunit marker vaccine and companion diagnostic test

The development of a classical swine fever (CSF) subunit marker vaccine, based on viral envelope glycoprotein E2, and a companion diagnostic test, based on a second viral envelope glycoprotein E(RNS), will be described. Important properties of the vaccine, such as onset and duration of immunity, and prevention of horizontal and vertical transmission of virus were evaluated. A single dose of the vaccine protected pigs against clinical signs of CSF, following intranasal challenge with 100LD(50) of virulent classical swine fever virus (CSFV) at 2 weeks after vaccination. However, challenge virus transmission to unvaccinated sentinels was not always completely inhibited at this time point. From 3 weeks up to 6 months after vaccination, pigs were protected against clinical signs of CSF, and no longer transmitted challenge virus to unvaccinated sentinels. In contrast, unvaccinated control pigs died within 2 weeks after challenge. We also evaluated transmission of challenge virus in a setup enabling determination of the reproduction ratio (R value) of the virus. In such an experiment, transmission of challenge virus is determined in a fully vaccinated population at different time points after vaccination. Pigs challenged at 1 week after immunization died of CSF, whereas the vaccinated sentinels became infected, seroconverted for E(RNS) antibodies, but survived. At 2 weeks after vaccination, the challenged pigs seroconverted for E(RNS) antibodies, but none of the vaccinated sentinels did. Thus, at 1 week after vaccination, R1, and at 2 weeks, R=0, implying no control or control of an outbreak, respectively. Vertical transmission of CSFV to the immune-incompetent fetus may lead to the birth of highly viraemic, persistently infected piglets which are one of the major sources of virus spread. Protection against transplacental transmission of CSFV in vaccinated sows was, therefore, tested in once and twice vaccinated sows. Only one out of nine once-vaccinated sows transmitted challenge virus to the fetus, whereas none of the nine twice-vaccinated sows did. Finally, our data show that the E(RNS) test detects CSFV-specific antibodies in vaccinated or unvaccinated pigs as early as 14 days after infection with a virulent CSF strain. This indicates that the E2 vaccine and companion test fully comply with the marker vaccine concept. This concept implies the possibility of detecting infected animals within a vaccinated population.