Mucosal immune responses in peri-parturient dairy cattle.

The objectives of this study were to evaluate mucosal immune responses in peripartum Holstein cows, to assess the impact of intranasal modified live viral (MLV) vaccination on mucosal immunity, and to explore the relationship between genotype and peripartum immune responses. Eighty multiparous Holstein cows were randomized to receive either: 1) intranasal MLV tri-valent viral vaccine 18-24 days prior to expected calving (DC); 2) the same vaccine within twelve hours after parturition (F); 3) vaccine at both time points (DCF), or 4) no vaccine (CON). Nasal secretions and sera were collected from all cattle pre-vaccination and on multiple days before and after calving to determine concentrations of interferon beta (IFN-beta) and IFN-gamma and bovine herpesvirus-1 (BHV-1-) and bovine respiratory syncytial virus (BRSV-) specific IgA in nasal secretions, and BHV-1 and BRSV serum neutralizing (SN) titers. Cows were genotyped by bead-based microarray, genotypes were used to categorize previously established health traits, and relationships between immune responses and genotype were evaluated. There was no significant effect of vaccination on immune responses, although all vaccinated groups demonstrated numerically increased IFN-gamma within four days post vaccination. There was a significant (P <0.0001) time effect on nasal IgA in CON, F, and DCF groups, with the highest nasal IgA titers measured post calving. There was a significant (P <0.0001) time effect on nasal IFN-beta in all groups. Significant relationships between genotype and immune response were not detected. Contrary to previous reports of systemic immunosuppression, bovine mucosal responses appear to be intact in the peripartum period.

Effect of serum total protein concentration on early-life health and growth of dairy calves.

OBJECTIVE: To assess the effect of serum total protein (STP) concentration on the early-life health and growth of dairy calves. ANIMALS: 39,619 neonatal Holstein, Jersey, and crossbred calves from 15 dairy operations. PROCEDURES: Calves arrived at a single calf-raising facility at approximately 2 days old. Each calf was weighed at facility arrival, and a blood sample was obtained the next day for determination of STP concentration by refractometry. All calves were managed in a standard manner, and health events were recorded for 120 days. A subset of 3,214 calves was weighed at 120 days old, and the average daily gain (ADG) was calculated. Linear mixed models were used to assess the effect of STP concentration on specific health events. RESULTS: STP concentration was associated with the incidences of death, diarrhea, pneumonia, and whether a calf received IV fluid therapy. In general, the incidence of adverse health events decreased as STP concentration increased to 6.0 g/dL, plateaued at STP concentrations between 6.0 and 8.5 g/dL, and increased at STP concentrations > 8.5 g/dL. Although STP concentration was not associated with ADG, the ADG for Holsteins increased as STP concentration increased to 8.5 g/dL and then decreased at STP concentrations > 8.5 g/dL. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that, for neonatal dairy calves, an STP concentration between 6.0 and 8.5 g/dL was optimal for health and growth, and calves with an STP concentration < 5.0 or > 8.5 g/dL should be considered at high risk for adverse health events.

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.

Neonatal immunology.

The field of neonatal immunology and calf vaccination is going through a revolution in veterinary medicine. The purpose of this article is to give an overview of basic neonatal immunology and principles of vaccination as they relate to beef and dairy calves. Opinions on when and what to vaccinate calves for vary widely among experts; therefore, this article focuses primarily on the documented literature. It is likely that vaccination approaches that might be effective or economic for one herd may not work for another.

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.

Evaluation of two antimicrobial therapies in the treatment of Leptospira borgpetersenii serovar hardjo infection in experimentally infected cattle.

This study demonstrated the ability of the antimicrobials tulathromycin (Draxxin) and ceftiofur crystalline free acid sterile suspension (Excede) to clear the spirochete Leptospira borgpetersenii serovar hardjo type hardjo-bovis (L. hardjo-bovis) from experimentally infected cattle. Treatment with tulathromycin resulted in clearance of L. hardjo-bovis organisms from the urine and kidney tissue of all animals (9 of 9), and treatment with ceftiofur crystalline free acid resulted in clearance of the organisms from the urine of 8 of 10 heifers and the kidney tissue of all 10 animals. In contrast, 10 of 10 placebo-treated cattle had L. hardjo-bovis organisms in their urine and 8 of 10 had the organisms in kidney tissue.

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.

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.

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.

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.

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.

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 project's 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 project's 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.

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.