Objective:To determine the effectiveness of canine parvovirus (CPV-2) monoclonal antibody (CPMA) to prevent CPV-2 disease after an experimental challenge to support a label claim for prophylactic use. Methods:25 Beagle pups aged 7 to 8 weeks were randomized to CPMA-treated (n = 20) or PBS-treated control (5) groups. One day after SC administration of PBS or CPMA (0.1 mL/kg) on study day (SD) 0, all pups were challenged by intranasal administration of virulent CPV-2b. Personnel masked to treatment groups monitored clinical signs, including rectal temperature, vomiting, and/or abnormal feces, over SD 2 through SD 14. Samples collected included sera, whole blood, and feces to assess antibody responses, lymphopenia, and fecal shedding of CPV-2, respectively. The CPV-2 disease case definition included at least 3 of 4 criteria: fever of 39.7 °C (103.4 °F) or greater, decreased lymphocytes to 50% of baseline or below, presence of diarrhea, and detection of CPV-2 virus in feces. Results:All 5 control pups developed parvovirosis and met the CPV-2 case definition. In contrast, none of the 19 CPMA prophylactically treated pups developed more than 1 of the criteria for CPV-2 disease. One pup infected with CPV-2 via environmental exposure and treated therapeutically was also protected against CPV-2 disease signs. Conclusions:Prophylactic CPMA treatment successfully protected all pups from experimental CPV-2 disease. Clinical Relevance:Prophylactically administered CPMA provides a reasonable expectation of passive protection of naïve pups against parvovirosis in high-risk settings, such as outbreak situations.
Objective:To determine initial antibody titer, degradation profile, and duration of passive antibody blockade of active immunization by modified-live viral (MLV) canine parvovirus (CPV-2) vaccine following CPV monoclonal antibody (CPMA) prophylactic subcutaneous (SC) administration to CPV-2-naïve puppies. Methods:Purpose-bred, CPV-2-seronegative male and female Beagle dogs, 7 to 8 weeks of age, were randomized to CPMA treatment (n = 13) and control (7) groups. Dogs were commingled and group housed in a shower-in/shower-out facility. At study day 0, dogs were administered either 0.1 mL/kg body weight CPMA SC or an equivalent volume of saline. Sera collected weekly over 140 days were assayed via hemagglutination inhibition and serum virus neutralization. All dogs were administered a commercially available MLV vaccine containing CPV-2 in combination with other core vaccine viruses at 3-week time points beginning at study day 42. Results:All control dogs remained seronegative through day 42 and seroconverted to CPV-2 after the initial dose of MLV vaccine. By study day 1, the CPMA-treated group showed a mean passive hemagglutination inhibition titer of 1,674. The average degradation rate was calculated at R2 = 0.97, with a mean half-life of 18.9 days. Twelve of 13 (92%) in the treated group seroconverted after a fourth vaccination on day 105. Conclusions:Prophylactic CPMA at 0.1 mL/kg body weight SC can block active CPV-2 immunization for 15 weeks when given to seronegative puppies. Clinical Relevance:Initial puppy vaccination series should be extended after CPMA prophylactic use.
OBJECTIVE:To evaluate the effectiveness of canine parvovirus monoclonal antibody (CPMA) as a treatment against canine parvovirus (CPV-2)-induced mortality and to support USDA product licensure. ANIMALS:28 purpose-bred Beagle dogs aged 8 weeks were randomized to the treated (n = 21) or control (7) group. METHODS:Dogs were challenged intranasally with 104.2 TCID50 virulent CPV-2b on Day 0 and monitored for 14 days for fecal viral shed and clinical disease. All dogs began shedding CPV-2 on Day 4 and were treated intravenously with a single dose of either CPMA (0.2 mL/kg) or saline (equal volume). No additional treatments were given to either group. Feces and sera were collected for quantitative analysis of fecal viral shed (hemagglutination) and antibody responses (hemagglutination inhibition and dot-blot ELISA), respectively. Dogs were monitored twice daily for parameters including lymphopenia, fever, vomiting, abnormal feces, inappetence, and lethargy. Humane endpoints triggered euthanasia by a veterinarian masked to treatment groups. The primary outcome variable was prevention of mortality as compared to controls. RESULTS:Mortality was prevented in all CPMA-treated dogs compared to 57% mortality in the control group (P = .0017, Fisher exact test). Canine parvovirus monoclonal antibody-treated dogs also experienced less severe and/or shorter durations of diarrhea, fever, vomiting, CPV-2 shedding in feces, and lymphopenia. Both groups showed similar immunoglobulin M responses as measured by semiquantitative analysis. CLINICAL RELEVANCE:Intravenous administration of CPMA can effectively improve clinical outcome when administered early in CPV-2 disease. Canine parvovirus monoclonal antibody treatment after proven infection does not interfere with adaptive immunity.
Since first emerging in the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. The severity of disease is variable, and coinfection by other respiratory pathogens is an important factor in the degree of morbidity and mortality. The first influenza vaccine for dogs, an inactivated vaccine containing CIV subtype H3N8, was conditionally approved by the U. S. Department of Agriculture (USDA) for licensure in May 2009 and fully licensed in June 2010. This study evaluates the efficacy of this vaccine to reduce the severity of illness in dogs cochallenged with virulent CIV and Streptococcus equi subsp. zooepidemicus.
Twelve cats were vaccinated at 8 and 11 weeks of age with a commercially available inactivated FeLV vaccine (Nobivac FeLV, Intervet/Schering-Plough Animal Health). Eleven cats served as age-matched, placebo-vaccinated controls. All cats were kept in isolation for 2 years after vaccination and were then challenged with virulent FeLV to evaluate vaccine efficacy and duration of immunity. Cats were monitored for 12 weeks after challenge for development of persistent viremia using a commercial FeLV p27 ELISA. Persistent viremia developed in all 11 (100%) of the control cats, whereas 10 of 12 (83%) vaccinated cats were fully protected from persistent viremia following challenge. The results demonstrate that the vaccine used in this study protects cats from persistent FeLV viremia for at least 2 years after vaccination.
Canine influenza virus (CIV) subtype H3N8 has emerged as a new pathogen with sustained transmission in the dog population in the United States. In this study, we report the experimental induction of respiratory disease in dogs using three CIV field isolates. Young (14 to 15 weeks of age) CIV-seronegative pups were challenged with one of three CIV isolates and monitored for clinical signs of respiratory disease, nasal virus shedding, seroconversion, lung lesions, and virus isolation from the lower respiratory tract. The challenged pups developed clinical signs and lung lesions typical of influenza virus infection, shed virus in their nasal secretions for 7 to 8 days after challenge, and exhibited serum antibodies at 7 and 14 days after challenge. Lung tissues and tracheal swabs collected at 3 and 6 days after challenge exhibited active virus replication. These results demonstrate that CIV causes respiratory disease in dogs.
Canine influenza virus (CIV) subtype H3N8 is an emerging pathogen with sustained horizontal transmission in the dog population in the United States. This study evaluated the efficacy of an inactivated CIV vaccine in 6- to 8-week-old beagle pups challenged with virulent CIV. One group of CIV-seronegative pups was vaccinated with two doses of a CIV vaccine 3 weeks apart; a second group of pups received adjuvanted placebo as a control. Blood samples were collected at various times to determine antibody titers. All pups were challenged with a virulent CIV isolate 13 days after the second vaccination and monitored for clinical signs of respiratory disease, virus shedding, and lung consolidation. Vaccinated pups developed hemagglutination inhibition antibody titers after vaccination. The severity of clinical signs (P < .001) and the magnitude and duration of virus shedding (P < .0001) were significantly lower in vaccinated pups compared with control pups. These results demonstrate that the CIV vaccine used in this study provides protection against virulent CIV challenge in dogs.
Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.
Enterotoxigenic Escherichia coli is one of the primary etiologic agents for diarrhea in neonatal calves. Immunization of dams can provide passive protection in neonatal calves; antibodies transferred through colostrum block colonization of bacteria, thereby preventing disease. In this study, healthy pregnant heifers were vaccinated at approximately 3 months of gestation with either a polyvalent oil-adjuvanted vaccine containing inactivated coronavirus, rotavirus, E. coli K99 subunit antigen, and Clostridium perfringens b and e toxoid or normal saline as a placebo. Calves were allowed to nurse immediately after birth, were orally challenged with virulent heterologous enterotoxigenic E. coli at 1 day of age, and were observed for clinical signs of scours for 10 days. Signs of severe scours were noted in 75% of control calves and 28.6% of vaccinates, and the severity of scours was significantly higher (P = .0382) in the control group. The mortality rate was significantly higher (P = .0007) in the control group (80%) than in the vaccinate group (14%). These findings indicate that the vaccination of pregnant heifers at as early as 3 months of gestation (6 months before calving) provides passive protection in neonatal calves against colibacillosis.
Introduction Mycoplasma hyopneumoniae causes enzootic pneumonia that primarily affects growing pigs. Although the disease is nonfatal, it causes substantial losses attributable to reduced growth performance, increased susceptibility to secondary bacterial pneumonia, and potentiation of PRRSV-induced pneumonia.1, 2 Both cell-mediated and humoral immune responses appear to be important in providing protection against infection.3
Objectives: To evaluate the ability of needleless intradermal (ID) vaccines to induce protection against clinical disease and to compare the serological response of pigs to intramuscular (IM) and ID vaccination with Mycoplasma hyopneumoniae bacterins.Materials and methods: In each study, pigs seronegative for M hyopneumoniae were vaccinated either once or twice with M hyopneumoniae bacterins. The serological response to ID and IM vaccination was evaluated by the DAKO M hyopneumoniae blocking ELISA, and ID vaccine efficacy was tested by experimental respiratory challenge with a heterologous strain of virulent M hyopneumoniae.Results: Injection site reactions were minimal for all vaccines. Pigs vaccinated ID, either by needle or needleless injector, had significantly higher M hyopneumoniae antibody titers than did pigs vaccinated by IM injection. Pigs vaccinated by needleless ID injection had lower lung lesion scores and higher IgA and IgG titers in bronchoalveolar lavage fluid than did nonvaccinates following challenge. Protective immunity was established by 21 days postvaccination after a single ID dose of vaccine. Intradermal vaccination of swine for M hyopneumoniae by needleless injector was safe and efficacious, and did not require shaving or other preparation of the skin.Implications: Intradermal vaccination of swine with needleless injectors is feasible if vaccines are formulated for small doses (eg, 0.2 mL).
Condemnation of bovine livers because of liver abscesses causes a substantial economic loss to meat packers. Fusobacterium necrophorum and Arcano-bacterium pyogenes are believed to act synergistically to cause liver abscesses in cattle on high energy diets. A leukotoxin and a hemolysin have been shown to be important virulence factors of F. necrophorum and A pyogenes, respectively. The lysis of neutrophils and macrophages by the leukotoxin is thought to lead to the release of reactive oxygen radicals and cytolytic enzymes that damage the hepatic cells. The studies reported herein were done to test the efficacy of single-dose, bivalent F. necrophorum-A. pyogenes bacterin-toxoid to aid in the reduction of liver abscess incidence and severity under field conditions and natural challenge.
The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.