Victor S. Cortese

The efficacy of modified-live bovine respiratory syncytial virus vaccines in experimentally infected calves

The efficacy of modified-live (MLV) bovine respiratory syncytial virus (BRSV) vaccines and the correlates of vaccine-induced immunity were investigated in calves using a virulent experimental infection. Clinical disease and pulmonary pathology were significantly reduced, relative to unvaccinated controls, in calves vaccinated according to label directions with commercial multivalent MLV BRSV vaccines. In vitro assays of cellular immunity were more consistent correlates of vaccine associated protection than presence of post vaccination serum antibody. Most vaccinated calves shed virus, but peak virus titre was suppressed compared to unvaccinated controls, with clearance coincident with the simultaneous appearance of mucosal antibody, cytotoxic cells in the lung and anamnestic or primary serum antibody responses. Virus clearance in unvaccinated calves was coincident with the appearance of BRSV specific cytotoxic cells, before mucosal antibody was detected.

Genetic characterization of bovine viral diarrhea viruses isolated from persistently infected calves born to dams vaccinated against bovine viral diarrhea virus before breeding.

OBJECTIVE To collect and partially characterize strains of bovine viral diarrhea viruses(BVDVs) isolated from persistently infected (PI) calves born to vaccinated dams, determine genetic diversity of the isolated viruses, and identify regional distribution of genetically similar virus subpopulations. SAMPLE POPULATION 17 noncytopathic (NCP) BVDVs from PI calves from 11 herds of beef or dairy cattle. PROCEDURES Viral RNA was extracted from infected cell cultures, and BVDV-specific PCR primers were used to amplify > 1,000 bases of the viral genome. Derived sequences were used for molecular phylogenetic analyses to determine the viral genotype and viral genogroup and to assess genetic similarity among BVDVs. RESULTS Analysis of the 17 NCP strains of BVDV failed to detect a viral genotype or viral genogroup not already reported to exist in the United States. One virus was classified as genotype 1, genogroup 1b, and 16 viruses were classified as genotype 2, genogroup 2a. Genotype 2 strains were genetically diverse, and genetic similarities were not obvious among viruses from geographic regions larger than a small locale. CONCLUSIONS AND CLINICAL RELEVANCE Viruses isolated from herds where a genotype 1, genogroup 1a BVDV vaccine was administered prior to breeding were primarily genetically diverse genotype 2, genogroup 2a BVDVs. Vaccination with multiple BVDV genotypes may be needed to improve protection. Methods used in this study to obtain and analyze field strains are applicable to assessing efficacy of current BVDV vaccines. Candidates for future vaccines are viruses that appear able to elude the immune response of cattle vaccinated against BVDV with existing vaccines.

Efficacy of a flexible schedule for administration of a Leptospira borgpetersenii serovar Hardjo bacterin to beef calves

OBJECTIVE To determine whether a flexible vaccination regimen provides protection against challenge exposure with a virulent Leptospira borgpetersenii serovar Hardjo isolate. ANIMALS Fifty-five 4-week-old calves seronegative for antibodies against L borgpetersenii serovar Hardjo. PROCEDURES Calves were assigned to 3 groups and administered 2 doses of adjuvant (control calves; n = 11), 1 dose of serovar Hardjo bacterin and 1 dose of adjuvant (22), or 2 doses of the serovar Hardjo bacterin (22); there was a 16-week interval between dose administrations. Three weeks after the second dose, all calves were challenge exposed by use of conjunctival instillation of a heterologous strain of L borgpetersenii serovar Hardjo for 3 consecutive days. Urine samples for leptospiral culture were collected for 5 weeks after challenge exposure; at that time, all calves were euthanized and kidney samples collected for leptospiral culture. RESULTS Antibody titers increased in both leptospiral-vaccinated groups of calves. A significant increase in antibody titers against L borgpetersenii serovar Hardjo was detected after administration of the second dose of L borgpetersenii serovar Hardjo bacterin and challenge exposure. In 10 of 11 adjuvant-treated control calves, serovar Hardjo was isolated from both urine and kidney samples. Leptospira borgpetersenii serovar Hardjo was not isolated from the urine or kidney samples obtained from any of the 21 remaining calves that received 1 dose of bacterin or the 20 remaining calves that received 2 doses of bacterin. CONCLUSIONS AND CLINICAL RELEVANCE Protection in young calves was induced by vaccination with 1 or 2 doses of a serovar Hardjo bacterin.

Serologic response to Mannheimia haemolytica in calves concurrently inoculated with inactivated or modified-live preparations of M haemolytica and viral combination vaccines containing modified-live bovine herpesvirus type 1

OBJECTIVE To assess the serologic response of calves to inactivated and modified-live (ML) Mannheimia haemolytica (MH) preparations given alone and concurrently with combination viral vaccines containing ML bovine herpesvirus type 1 (BHV-1). ANIMALS 642 calves seronegative for BHV-1. PROCEDURES In experiment 1, 192 calves received 1 of 3 MH preparations alone or concurrently received 1 of 3 MH preparations and 1 of 4 combination viral vaccines. In experiment 2, 450 calves received 1 of 4 MH preparations alone or concurrently received 1 of 4 MH preparations and 1 of 5 combination viral vaccines. Pretreatment and posttreatment blood samples were processed to obtain serum, which was analyzed to detect concentrations of antibodies against MH leukotoxin and BHV-1. RESULTS In experiment 1, antibody titers against MH leukotoxin in calves receiving MH and ML virus vaccine appeared decreased, albeit nonsignificantly, compared with titers for calves receiving MH preparations alone. In experiment 2, all groups (except for 1) concurrently receiving an MH preparation and viral vaccine had a significant decrease in antibodies against MH leukotoxin. In both experiments, there was a significant decrease in the number of calves responding to MH leukotoxin when ML viral vaccine was coadministered. CONCLUSIONS AND CLINICAL RELEVANCE Coadministration of ML BHV-1 and MH preparations interfered with the serologic response to MH leukotoxin in calves seronegative for BHV-1. Serologic response to MH leukotoxin may be substantially improved in seronegative calves when MH vaccination is delayed until after calves have received a dose of ML BHV-1 vaccine.

Effect of constant exposure to cattle persistently infected with bovine viral diarrhea virus on morbidity and mortality rates and performance of feedlot cattle

OBJECTIVE To determine the effects of constant exposure to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) on health and performance of feedlot cattle. DESIGN 3 controlled trials. ANIMALS Crossbred feedlot cattle (trial 1, n = 184; trial 2, 138; trial 3, 138). PROCEDURES Weaned calves were or were not vaccinated against BVDV at feedlot arrival (trial 1) or 2 (trial 2) or 3 (trial 3) weeks before feedlot arrival. During trial 1, half of the calves were commingled with PI cattle throughout the feeding period. During trial 2, 63 calves were exposed to PI cattle before weaning and all calves were exposed to PI cattle throughout the feeding period. During trial 3, all study calves were exposed to PI cattle throughout the feeding period. Morbidity and mortality rates and average daily gain (ADG) data were analyzed. RESULTS During trial 1, calves maintained with PI cattle had a higher morbidity rate regardless of BVDV vaccination than did calves not exposed to PI cattle; however, for calves maintained with PI cattle, the morbidity rate for those vaccinated against BVDV was less than that for those not vaccinated against BVDV. During trial 2, calves exposed to PI cattle before weaning or vaccinated against BVDV had lower morbidity and mortality rates and increased ADG, compared with those for calves not exposed to PI cattle before weaning or vaccinated against BVDV. During trial 3, health and performance did not vary between calves that were and were not vaccinated against BVDV. CONCLUSIONS AND CLINICAL RELEVANCE Exposure of cattle to BVDV naturally or through vaccination before or at feedlot arrival mitigated the negative effects of constant exposure to PI cattle.

Comparison of interferon and bovine herpesvirus-1-specific IgA levels in nasal secretions of dairy cattle administered an intranasal modified live viral vaccine prior to calving or on the day of calving

Thirty-two Holstein cows were allocated to receive intranasal vaccination with modified live bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus (BRSV) and parainfluenza type 3 virus (PI3V) vaccine either two weeks prior to their projected calving date, or within 24h after calving. Nasal secretions were collected twice at a 12-h interval on the day prior to vaccination (day 0) and at 2, 4, 7, 10 and 14days post vaccination to measure interferon (IFN) alpha, IFN-beta, IFN-gamma, and BHV-1-specific IgA by ELISA. Serum neutralizing antibody titers to BHV-1 and BRSV were measured on days 0, 7, and 14. There was a significant treatment effect (p<0.0004) and interaction (p<0.05) on nasal BHV-1 IgA levels, with higher IgA levels in cows vaccinated within 24h after calving. There was a significant treatment effect on nasal IFN-gamma concentration (p<0.05) and on nasal total IFN concentration (p<0.05), with higher IFN-gamma and total IFN concentrations seen in cows vaccinated within 24h after calving. There was no significant treatment or interaction effect on nasal IFN-alpha or IFN-beta concentrations, or on serum neutralizing titers to BRSV. In spite of prior viral vaccination during the previous lactation, cows vaccinated on the day of calving responded to an intranasal viral vaccination with increased concentrations of IFN-gamma and increased titers of IgA following vaccination which was significantly higher than cows vaccinated precalving. This study is the first to examine respiratory mucosal responses in immunologically mature dairy cattle vaccinated intranasally before and after calving.

Comparison of reproductive protection against bovine viral diarrhea virus provided by multivalent viral vaccines containing inactivated fractions of bovine viral diarrhea virus 1 and 2

Bovine viral diarrhea virus (BVDV) is an important viral cause of reproductive disease, immune suppression and clinical disease in cattle. The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. BVDV negative beef heifers and cows (n = 122) were randomly assigned to one of four groups. Groups A-C (n = 34/group) received two pre-breeding doses of one of three commercially available multivalent vaccines containing inactivated fractions of BVDV 1 and BVDV 2, and Group D (n = 20) served as negative control and received two doses of saline prior to breeding. Animals were bred, and following pregnancy diagnosis, 110 cattle [Group A (n = 31); Group B (n = 32); Group C (n = 31); Group D (n = 16)] were subjected to a 28-day exposure to cattle persistently infected (PI) with BVDV (1a, 1b and 2a). Of the 110 pregnancies, 6 pregnancies resulted in fetal resorption with no material for testing. From the resultant 104 pregnancies, BVDV transplacental infections were demonstrated in 73 pregnancies. The BVDV fetal infection rate (FI) was calculated at 13/30 (43%) for Group A cows, 27/29 (93%) for Group B cows, 18/30 (60%) for Group C cows, and 15/15 (100%) for Group D cows. Statistical differences were observed between groups with respect to post-vaccination antibody titers, presence and duration of viremia in pregnant cattle, and fetal infection rates in offspring from BVDV-exposed cows. Group A vaccination resulted in significant protection against BVDV infection as compared to all other groups based upon outcome measurements, while Group B vaccination did not differ in protection against BVDV infection from control Group D. Ability of inactivated BVDV vaccines to provide protection against BVDV fetal infection varies significantly among commercially available products; however, in this challenge model, the inactivated vaccines provided unacceptable levels of BVDV FI protection.

Virus detection by PCR following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines

We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values <25 were observed in group 1 calves from PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

Review of the Michigan Upper Peninsula bovine viral diarrhea virus eradication project.

OBJECTIVE To evaluate the effects of a voluntary regional bovine viral diarrhea virus (BVDV) control project implemented in the Upper Peninsula of Michigan. DESIGN Longitudinal study. Sample-294 cattle producers and 11,917 cattle from the Upper Peninsula. PROCEDURES Producer participation was assessed to determine the effectiveness of the projects promotional and educational campaigns. Participating herds were screened for cattle persistently infected (PI) with BVDV by real-time reverse transcriptase PCR assay on ear notch specimens from all newborn calves and cattle that did not calve (bulls and young stock) during the year of enrollment. Responses to a survey administered to producers 4 years after project initiation were evaluated to assess the projects effect on BVDV management practices implemented by producers. RESULTS 294 of 495 (59%) known cattle producers in the Upper Peninsula participated in the project, and 11,917 cattle from 232 herds were tested for BVDV, of which 22 (0.18%) cattle from 9 (3.9%) herds were identified as PI with BVDV and euthanized or slaughtered. Of 140 survey respondents, 85 (61%) indicated they would test all new herd additions for BVDV, 83 (59%) would quarantine new herd additions for 30 days before introducing them to the main herd, and 81 (58%) would use the fact that their herd was free of cattle PI with BVDV for marketing purposes. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the project enhanced producer knowledge about BVDV and led to changes in producer behavior regarding BVDV management. Stakeholder engagement was as critical to project success as was increased BVDV knowledge.