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ABSTRACT: Bovine respiratory disease (BRD) is one of the most common infectious causes of morbidity and mortality in young dairy cattle. The objective of this randomized clinical trial was to determine the effectiveness of 1 or 2 doses of a 5-way, modified-live viral vaccine, administered to heifer calves before weaning to aid in the prevention of BRD. The hypotheses were that vaccination would reduce the incidence of BRD and mortality, and that 2 doses would be more effective than 1. A total of 2,874 heifer calves from 19 commercial dairy farms in Minnesota and Ontario were enrolled at 1 to 7d of age and were followed until 3mo of age. Calves were randomly assigned to receive a commercial, intramuscular, modified-live vaccine against bovine viral diarrhea virus types 1 and 2, bovine respiratory syncytial virus, bovine herpesvirus type 1, and parainfluenza virus type 3 at 15 to 21d of age (2wk only), 35 to 42d (5wk only), both 2 and 5wk, or sterile saline at both times (unvaccinated controls). The incidence of failure of passive transfer was 11 or 32%, using cut-points of serum total protein of 5.2 and 5.7g/dL, respectively. Overall, 22% of calves were treated at least once for BRD. The incidence risk of naturally occurring BRD was 7.7% before 2wk of age, 8.0% between 2 and 5wk, and 9.5% between 5wk and 3mo of age, and was not different between vaccination groups. Overall mortality throughout the 3-mo study period was 3.5%. Mortality was 1.6% before 2wk of age, 0.5% between 2 and 5wk, and 1.2% between 5wk and 3mo of age. The risk of mortality was not affected by vaccination. Mean average daily gain of 1.07kg/d from 5wk to 3mo of age was not different between vaccine groups. In this population of commercial, home-raised calves, with an overall low incidence of failure of passive transfer, intramuscular vaccination with a multivalent, modified live viral vaccine at 2 or 5wk of age or both was not associated with a decreased risk of BRD or mortality, or with growth until 3mo of age. Reasons for these findings may include interference by maternal antibodies, unresponsiveness of the neonatal immune system, timing of immunity relative to pathogen exposure, disease caused by pathogens other than the viruses in the vaccine, or herd immunity. However, in populations with higher incidence of failure of passive transfer or risk of BRD, calves with low levels of specific antibodies may respond differently to vaccination.
Journal of Dairy Science 09/2012; 95(11):6731-9. · 2.56 Impact Factor
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ABSTRACT: The aim of this study was to incorporate antigens from Mannheimia haemolytica culture supernatant, and an immune modulatory molecule, recombinant bovine C3d (rBoC3d), into immune stimulating complexes (ISCOMs) using neutravidin-biotin interaction. Biotinylated ISCOM matrix was generated using a commercial kit. The biotinylated ISCOM matrix was incubated with neutravidin and then centrifuged in a sucrose density gradient. The rBoC3d was expressed as an in vivo biotinylated protein and with a c-Myc tag (EQKLISEEDL) engineered to facilitate detection. The neutravidin-coated ISCOM matrix was incubated with biotinylated antigens from M. haemolytica culture supernatants and rBoC3d. To test the association among the neutravidin-coated ISCOM matrix, biotinylated antigens and rBoC3d, an analytical sucrose density gradient (10-40%, w/w) was performed. The experimental formulations were run in SDS-PAGE gels under reducing conditions. For Western immunoblot analysis, polyclonal bovine antiavidin, monoclonal anti-c-Myc, monoclonal antileukotoxin, and anti-GS60 antibodies were used to detect the presence of neutravidin, rBoC3d, leukotoxin, and GS60 antigens, respectively. By taking advantage of the biotin-neutravidin interaction, not only leukotoxin but also the recombinant immunomodulatory molecule, rBoC3d, was incorporated into ISCOM particles.
Biotechnology and Applied Biochemistry 05/2011; 58(3):198-202. · 1.53 Impact Factor
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05/2010: pages 15 - 32; , ISBN: 9780470958209
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ABSTRACT: Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. The oral route is problematic in cattle and other ruminants where antigen degradation in the rumen is likely, prior to transit to the intestine. On the other hand, rumination can be exploited for exposure of nasopharyngeal tissues during cudding if vaccine antigen is expressed by a fibrous feed like alfalfa. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. Intranasal vaccination is an alternative approach for use in pre-ruminating calves. Intranasal administration of ISCOMs carrying soluble antigens of M. haemolytica, including native Lkt, induced Lkt specific IgA in nasal secretions after vaccination at 4 and 6 weeks of age. Subcutaneous (s.c.) administration of the same vaccine induced Lkt specific IgG in both serum and nasal secretions, whereas s.c. administration of a commercial M. haemolytica vaccine did not. Regardless of the vaccination strategy employed it is difficult to assess the immunogenicity of mucosally administered vaccines because production of secreted antibodies tends to be transient, and they do not persist on the mucosal surface in the absence of ongoing antigenic stimulation. An additional challenge is demonstration of vaccine efficacy in response to experimental infection. Protection of the mucosally vaccinated animal will most probably result from recall response, which may not amplify sufficiently to counter the effects of experimental pulmonary delivery of a large bolus of virulent bacteria, even though the response would suffice over the more prolonged and gradual infection that occurs in natural induction of pneumonia.
Veterinary Immunology and Immunopathology 11/2008; 128(1-3):192-8. · 2.08 Impact Factor
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ABSTRACT: Mannheimia haemolytica is the principal bacterium isolated from respiratory disease in feedlot cattle and is a significant component of enzootic pneumonia in all neonatal calves. A commensal of the nasopharynx, M. haemolytica is an opportunist, gaining access to the lungs when host defenses are compromised by stress or infection with respiratory viruses or mycoplasma. Although several serotypes act as commensals, A1 and A6 are the most frequent isolates from pneumonic lungs. Potential virulence factors include adhesin, capsular polysaccharide, fimbriae, iron-regulated outer membrane proteins, leukotoxin (Lkt), lipopolysaccharide (LPS), lipoproteins, neuraminidase, sialoglycoprotease and transferrin-binding proteins. Of these, Lkt is pivotal in induction of pneumonia. Lkt-mediated infiltration and destruction of neutrophils and other leukocytes impairs bacterial clearance and contributes to development of fibrinous pneumonia. LPS may act synergistically with Lkt, enhancing its effects and contributing endotoxic activity. Antibiotics are employed extensively in the feedlot industry, both prophylactically and therapeutically, but their efficacy varies because of inconsistencies in diagnosis and treatment regimes and development of antibiotic resistance. Vaccines have been used for many decades, even though traditional bacterins failed to demonstrate protection and their use often enhanced disease in vaccinated animals. Modern vaccines use culture supernatants containing Lkt and other soluble antigens, or bacterial extracts, alone or combined with bacterins. These vaccines have 50-70% efficacy in prevention of M. haemolytica pneumonia. Effective control of M. haemolytica pneumonia is likely to require a combination of more definitive diagnosis, efficacious vaccines, therapeutic intervention and improved management practices.
Animal Health Research Reviews 01/2008; 8(2):117-28.
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ABSTRACT: Colostrum-deprived Holstein calves were vaccinated at 2 and 4 wk of age with a Pasteurella haemolytica A1 culture supernatant vaccine to determine whether active immune responses and protection could be induced in this age group in the absence of maternal antibodies. All calves responded to vaccination with high titers of IgM antibodies to capsular polysaccharide within 1 wk of primary vaccination. Mean titers of IgG1 and IgG2 antibodies to this antigen increased significantly by 2 wk after secondary vaccination, but peak antibody titers were low. All of the vaccinated calves seroconverted with production of leukotoxin-neutralizing antibodies, but peak antibody titers were low. Vaccinated calves experienced considerable lung damage after experimental challenge, but survival rate, clinical scores, and percent lung involvement were significantly better than those of control (placebo-injected) calves.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire 02/2000; 64(1):3-8. · 0.94 Impact Factor
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ABSTRACT: The potential and limitations of early calfhood vaccination to induce active immunity to Pasteurella haemolytica A1 in conventional colostrum fed calves were investigated. Holstein dairy calves (n = 29) were vaccinated at 2 and 4 weeks of age, or at 6 and 8 weeks of age with a commercial culture supernatant vaccine (Presponse, Langford Inc., Guelph, Ont., Canada), or remained unvaccinated as controls. Serum antibody titres were measured using an indirect bacterial agglutination assay, a leukotoxin neutralization assay, and enzyme immunoassays for antibodies of the IgM, IgG1, and IgG2 isotypes binding purified capsular polysaccharide of P. haemolytica A1. Seroconversion (fourfold or greater increase in serum antibody titre) rates were compared using Fisher's exact test. The effects of passive antibody titres and age on response to vaccination were assessed by linear modelling. Vaccination at 2 and 4 weeks of age was associated with 40%, and 0% of calves seroconverting on the basis of agglutinating antibody titres, and leukotoxin neutralizing titres respectively, and 50%, 0%, and 0% seroconverting on the basis of IgM, IgG1 and IgG2 antibodies to capsular polysaccharide, respectively. Agglutinating antibody responses were not related to prevaccination antibody titres, or to age at vaccination. Higher responses (p = 0.08) to leukotoxin were observed in older calves (after taking differences in prevaccination titres into account). Statistical analyses of responses to capsular polysaccharide among calves with comparable prevaccination IgG1 antibody titres revealed significantly higher IgM, IgG1 and IgG2 responses in older calves. Rising titres of IgM antibodies in nonvaccinated calves after 5 weeks of age suggest natural exposure to P. haemolytica A1 or antigens which result in serologic cross-reactions as a means of priming immune responses.
Vaccine 01/1999; 16(20):2018-25. · 3.77 Impact Factor
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ABSTRACT: The potential to increase passive serum antibody titres to a polysaccharide antigen in neonates, by preparturient vaccination of the dams was investigated. Dairy cows in five private herds were vaccinated with a commercial Pasteurella haemolytica culture supernatant vaccine (Presponse, Langford Inc.), at 6 and 3 weeks before their calculated due dates. Dams' sera, colostral whey, and post-colostral calf sera were assayed for antibodies of the IgG1 isotype binding purified capsular polysaccharide of P. haemolytica A1, using an enzyme immunoassay. Antibody titres were analyzed using the General Linear Model procedure (Statistical Analysis Systems Institute Inc.). Vaccinated dams had a significant increase in serum antibody titre after vaccination compared with non-vaccinates (P <0.01), and their antibody titres in colostral whey were significantly higher (P <0.05). Calves of vaccinated dams had significantly higher passive antibody titres than those of non-vaccinates (P <0.01) in all herds.
Veterinary Immunology and Immunopathology 03/1996; 50(1-2):67-77. · 2.08 Impact Factor
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ABSTRACT: Dairy cows from five herds were assigned to receive a commercial Pasteurella haemolytica vaccine or no vaccine at all, administered at six and three weeks before parturition. Vaccination was associated with increased leukotoxin neutralizing serum antibody titers in the dams (p < 0.001), and with increased titers in colostrum (p < 0.001). Vaccination of dams also had a significant association with increased passive leukotoxin neutralizing antibody titers in their calves (p < 0.001). Vaccination was also associated with increased indirect agglutinating antibody titers in serum of the dams (p < 0.001). In the analysis of agglutinating antibody titers in colostral whey the interaction "vaccination*herd" was found to be significant (p < 0.001), indicating that the effects of vaccination on colostral titers were not consistent from herd to herd. The analysis was repeated, stratifying by herd. Vaccination was associated with increased agglutinating antibody titers in colostrum (p < 0.05) in three herds of the five in the study. In two of these three herds there were significant increases in passive neonatal titers associated with vaccination. In the remaining herd the mean IgG1 level in the calves was consistent with failure of passive transfer of immunoglobulins (IgG1 < 8.0 g/L). These results suggest that preparturient vaccination of dairy cows can induce modest increases in passive antibody titers to antigens of Pasteurella haemolytica in their calves, but the antigen of interest and the population being studied can affect the outcome.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire 01/1994; 58(1):31-5. · 0.94 Impact Factor
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ABSTRACT: Recognition of the mucosal portal of entry for many infectious diseases and of the relevance of mucosal immune response to protection has encouraged the development of vaccines administered by mucosal routes, principally oral and intranasal, for stimulation of intestinal and nasopharyngeal lymphoid tissues respectively. The oral route is problematic in cattle and other ruminants where antigen degradation in the rumen is likely, prior to transit to the intestine. On the other hand, rumination can be exploited for exposure of nasopharyngeal tissues during cudding if vaccine antigen is expressed by a fibrous feed like alfalfa. An increase in anti-leukotoxin (Lkt) IgA was demonstrated in nasal secretions of calves following feeding of alfalfa expressing a truncated Lkt50 from Mannheimia haemolytica, and there is evidence suggesting that such vaccination may protect against experimentally induced pneumonia. Intranasal vaccination is an alternative approach for use in pre-ruminating calves. Intranasal administration of ISCOMs carrying soluble antigens of M. haemolytica, including native Lkt, induced Lkt specific IgA in nasal secretions after vaccination at 4 and 6 weeks of age. Subcutaneous (s.c.) administration of the same vaccine induced Lkt specific IgG in both serum and nasal secretions, whereas s.c. administration of a commercial M. haemolytica vaccine did not. Regardless of the vaccination strategy employed it is difficult to assess the immunogenicity of mucosally administered vaccines because production of secreted antibodies tends to be transient, and they do not persist on the mucosal surface in the absence of ongoing antigenic stimulation. An additional challenge is demonstration of vaccine efficacy in response to experimental infection. Protection of the mucosally vaccinated animal will most probably result from recall response, which may not amplify sufficiently to counter the effects of experimental pulmonary delivery of a large bolus of virulent bacteria, even though the response would suffice over the more prolonged and gradual infection that occurs in natural induction of pneumonia.
Veterinary Immunology and Immunopathology.
