The duration of immunity to an inactivated adjuvanted canine parvovirus vaccine. A 52 and 64 week postvaccination challenge study

Dogs were successfully isolated for a period of either 52 or 64 weeks following vaccination with an inactivated, adjuvanted canine parvovirus-2 vaccine. Antibody persisted in all ten vaccinated dogs, although in one case by 52 weeks postvaccination only virus neutralizing antibody, and not hemagglutination-inhibiting antibody, could be detected. Sentinel unvaccinated dogs housed alongside the vaccinated dogs throughout the study remained free of canine parvovirus-2 antibody until challenged. Upon oral challenge with canine parvovirus-2 infected material all unvaccinated dogs developed one or more signs of canine parvovirus-2 disease, shed virus and developed antibody. None of the vaccinated dogs became overtly sick. Of the five vaccinated dogs challenged 52 weeks after vaccination, three shed virus and one showed a significant rise in antibody. At 64 weeks after vaccination only one of the five challenged dogs shed virus and showed a boost in antibody titer.     

Experimental respiratory disease in dogs due to Bordetella bronchiseptica.

Young dogs of two age groups, six weeks and 12 weeks respectively, were infected by aerosol with a strain of Bordetella bronchiseptica which had been isolated from a dog with pneumonia. Clinical respiratory disease characterised by coughing and in some cases purulent nasal discharge was induced in both groups of infected dogs and also in dogs kept in contact. B bronchiseptica was recovered from the nasal cavity, trachea, bronchi and lung parenchyma of infected and contact animals. At necropsy, masses of Gram-negative bacteria were found trapped in the cilia of the respiratory epithelia and there was an exudate containing neutrophils in the mucosae of the respiratory tract at all levels. A close similarity was noted between the lesions produced in the dog and those described in pertussis infection in man. Experimental respiratory disease in the dog due to B bronchiseptica may offer a model system for the study of the human disease.     

Effect of vaccination on experimental infection with Bordetella bronchiseptica in dogs

OBJECTIVE: To determine comparative efficacy of vaccines administered IM and intranasally, used alone or sequentially, to protect puppies from infection with Bordetella bronchiseptica and determine whether systemic or mucosal antibody response correlated with protection. DESIGN: Randomized controlled trial. ANIMALS: 50 specific-pathogen-free Beagle puppies. PROCEDURE: In 2 replicates of 25 dogs each, 14-week-old puppies that were vaccinated against canine distemper virus and parvovirus were vaccinated against B bronchiseptica via intranasal, IM, intranasal-IM, or IM-intranasal administration or were unvaccinated controls. Puppies were challenge exposed via aerosol administration of B bronchiseptica 2 weeks after final vaccination. Clinical variables and systemic and mucosal antibody responses were monitored for 10 days after challenge exposure. Puppies in replicate 1 were necropsied for histologic and immunohistochemical studies. RESULTS: Control puppies that were seronegative before challenge exposure developed paroxysmal coughing, signs of depression, anorexia, and fever. Vaccinated puppies (either vaccine) that were seronegative before challenge exposure had fewer clinical signs. Puppies that received both vaccines had the least severe clinical signs and fewest lesions in the respiratory tract. Vaccinated dogs had significantly higher concentrations of B bronchiseptica-reactive antibodies in serum saliva before and after challenge. Antibody concentrations were negatively correlated with bacterial growth in nasal cavity and pharyngeal samples after challenge exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Parenterally and intranasally administered vaccines containing B bronchiseptica may provide substantial protection from clinical signs of respiratory tract disease associated with infection by this bacterium. Administration of both types of vaccines in sequence afforded the greatest degree of protection against disease.     

Vaccination against paratuberculosis of lambs already infected experimentally with Mycobacterium avium subspecies paratuberculosis

OBJECTIVE: To assess the protective value of a live-attenuated vaccine in sheep already exposed to Mycobacterium avium subsp paratuberculosis and to investigate the progression of a systemic immune response in experimentally infected sheep. STUDY DESIGN: Twenty-eight lambs, aged 1 to 1.5 months, were dosed via stomach tube with approximately 4.4 x 10(8) M a paratuberculosis organisms. Two weeks later, 14 of these 28 animals received subcutaneous injections of 1 mL of a live-attenuated vaccine. Thirteen additional lambs were neither dosed nor vaccinated (negative controls). Antigen-induced production of IFN-gamma in blood, and antibody concentrations in serum were sequentially monitored in vaccinated, unvaccinated and control animals for 1 year. Each sheep was examined for infection by an IS900-based PCR test on samples of ileum and ileocaecal lymph node and histological examination at the time of necropsy. RESULTS: Seven of 14 unvaccinated and two of 14 vaccinated sheep developed clinical paratuberculosis that was later confirmed by histological examination and/or the IS900-based PCR test. The granulomatous inflammation in the jejunal and ileal mucosa was less severe in vaccinated than in unvaccinated sheep. Acid-fast organisms were detected only in the unvaccinated group. The PCR assay on ileal samples gave positive reactions in two vaccinated and eight unvaccinated sheep. Both the antibody response and IFN-gamma response were detected earlier and were more substantial in vaccinated than in unvaccinated sheep. Furthermore, in experimentally infected but unvaccinated sheep, the IFN-gamma concentrations were higher in those animals without acid-fast organisms than in those with them. CONCLUSIONS: Vaccination of lambs with live-attenuated vaccine 2 weeks after oral inoculation with M a paratuberculosis stimulated the host response against the organism and led to a reduced mycobacterial burden. The diminished IFN-gamma responses in experimentally infected sheep with acid-fast organisms suggest a positive relationship between the magnitude of the systemic cell-mediated immune response and an animal's ability to control infection.     

Studies of the efficacy of a novel intranasal vaccine against feline bordetellosis

A novel intranasal vaccine against disease caused by Bordetella bronchiseptica in cats was tested in a series of three experiments. In the first experiment a vaccinated group and an unvaccinated control group of kittens were challenged by the aerosol route with virulent B bronchiseptica three weeks after they had been vaccinated. The control kittens developed upper respiratory tract signs typical of feline B bronchiseptica infection, including rhinitis, a serous ocular and nasal discharge, fever, sneezing and coughing. The mean (sd) clinical score for the cats in the unvaccinated control group was 19.5 (5.4) compared with 1.53 (1.9) for the vaccinated group. In the second experiment vaccinated kittens were challenged with virulent B bronchiseptica 72 hours after they were vaccinated. Their mean clinical score was 2.76 (2.62) compared with 13.4 (3.33) for the control group. In the final experiment, vaccinated and unvaccinated control cats were challenged after six or 12 months. After six months the mean clinical scores were 13.9 (4.7) for the control group, compared with 1.33 (1.56) for the vaccinated group, and after 12 months the scores were 9.92 (5.79) for the control group compared with 0.92 (0.89) for the vaccinated group.     

An evaluation in pigs of Nobi-Vac AR and an experimental atrophic rhinitis vaccine containing P multocida DNT-toxoid and B bronchiseptica

The trial involved eight large white sows obtained from a closed experimental specific pathogen free herd. Four sows (two each for an experimental vaccine and for Nobi-Vac AR) were vaccinated twice (eight weeks and two weeks before parturition) with 2 ml of vaccine administered intramuscularly. Two unvaccinated sows were used as an infected control group and two unvaccinated sows served as an uninfected control group. Forty-six piglets (28 from vaccinated sows and 18 from unvaccinated sows) were challenged by intranasal instillation of Bordetella bronchiseptica at two days of age and Pasteurella multocida type D, dermonecrotic toxin at seven days of age. Among the infected control group some piglets died and there were clinical signs of pneumonia and severe turbinate atrophy. In the vaccinated groups the results showed that immunisation of the pregnant sows had provided a good level of antibodies, which were transmitted to their offspring. There was a significant reduction in the clinical signs and no lesions were observed in the group vaccinated with the experimental vaccine and only moderate atrophy of the turbinates in the Nobi-Vac AR group. B bronchiseptica and P multocida were never recovered from the lungs of the vaccinated groups and in the nasal cavities their frequency declined with age.     

Protective efficacy of a live attenuated Mycoplasma hyopneumoniae vaccine with an ISCOM-matrix adjuvant in pigs

An attenuated Mycoplasma hyopneumoniae vaccine that requires intrathoracic administration is commercially available for use against mycoplasmal pneumonia in China. Given the limitations of such a route of administration, this study was undertaken to assess the capacity of an ISCOM-matrix adjuvant to enhance immunogenicity following intramuscular use. Immune responses in pigs following vaccination and subsequent intra-tracheal bacterial inoculation were examined using lymphocyte proliferation, serology and mucosal IgA in both nasal and saliva swabs.Vaccination induced clear lymphocyte proliferation, but only slight serum antibody responses although these were significantly increased following experimental infection. Mucosal IgA was not detected in either nasal or salivary secretions. Following bacterial challenge, animals vaccinated with the adjuvant-containing live vaccine exhibited less severe pulmonary lesions (median score 3.67) than unvaccinated pigs (median score 13.58). The degree of ciliary loss on the respiratory tract surface was reduced in vaccinated pigs compared with experimentally infected controls. The findings indicated that the adjuvant vaccine administered IM provided protection against experimentally induced mycoplasmal pneumonia and could have commercial potential.     

Oronasal challenge of fattening pigs after vaccination with an inactivated Aujeszky's disease vaccine

Groups of pigs from vaccinated and unvaccinated sows were vaccinated once or twice between the ages of eight and 20 weeks with a commercial inactivated, oil adjuvanted Aujeszky's disease virus vaccine. Pigs were challenged by the oronasal route when 22 to 27 weeks old. Pigs from unvaccinated sows developed neutralising antibodies after vaccination but no seroconversion was detected in eight-week-old pigs or in 80 per cent of 15-week-old pigs from vaccinated sows. Challenge resulted in severe disease and weight loss in control pigs. In vaccinated animals the duration and severity of clinical signs and the amount of weight lost decreased with increasing serum neutralisation titres. The results indicate that parenteral vaccination at weaning with the vaccine described will not protect pigs at slaughter age against infection and disease, particularly if they were born from seropositive mothers.     

Protection of dogs for 13 months against Bordetella bronchiseptica and canine parainfluenza virus with a modified live vaccine

Twelve specific pathogen-free (spf) puppies were vaccinated intranasally with a bivalent, modified live vaccine against infectious tracheobronchitis (group 1) and six puppies of the same age and from the same source served as unvaccinated controls (group 2). Both groups were challenged with wild-type Bordetella bronchiseptica and canine parainfluenza virus by the aerosol route 56 weeks after group 1 had been vaccinated, and at the same time six 10-week-old spf puppies from the same source (group 3) were also challenged. Oronasal swabs were taken regularly before and after the challenge, for the isolation of bacteria and viruses, and the dogs were observed for clinical signs for three weeks after the challenge. The control dogs became culture-positive for B bronchiseptica and canine parainfluenza virus, but the isolation yields from the vaccinated group were significantly lower (P<0.05). The mean clinical scores of the vaccinated group were 61 per cent lower than the scores of group 2 (P=0.009), and 90 per cent lower than the scores of group 3 (P=0.001).     

Evaluation of an atrophic rhinitis vaccine under controlled conditions.

A vaccine containing inactivated cultures of Bordetella bronchiseptica, toxigenic Pasteurella multocida type D and dermonecrotic P multocida type D toxoid in an oil-in-water adjuvant was given to seven sows, with seven others acting as controls. Half the piglets in each litter were exposed intranasally when four days old to B bronchiseptica and when eight days old to toxigenic P multocida type D. There was considerably less sneezing in the litters of the vaccinated sows and when the piglets were 10 weeks old, only 18 per cent had deformed snouts compared with 74 per cent in the litters of the control sows. The average liveweight gain of the piglets born to vaccinated sows was significantly better (P less than 0.05) between two and 10 weeks of age than that of the piglets born to unvaccinated sows, although there were no significant lower respiratory tract lesions in either group. The conchal atrophy scores were significantly lower (P less than 0.001) in the piglets from the vaccinated sows and were negatively correlated (r = -0.37) with increasing liveweight gain. In the liters of the vaccinated sows, P multocida was not isolated from the nasal passages of the in-contact piglets and from only 7 per cent of those deliberately exposed compared with 65 per cent and 79 per cent, respectively, in the litters of the control sows. P multocida was isolated post mortem from the tonsils of 23 per cent of the piglets of vaccinated sows and from 87 per cent of those from unvaccinated sows.     

Protection of piglets against atrophic rhinitis by vaccinating the sow with a vaccine against Pasteurella multocida and Bordetella bronchiseptica

The efficacy of a new vaccine against atrophic rhinitis in pigs was tested in the Netherlands and Denmark. The vaccine contained protein dO (a truncated Pasteurella multocida toxin which is immunogenic and non-toxic), inactivated Bordetella bronchiseptica whole cells, and an adjuvant. The sows were either vaccinated intramuscularly with 2 ml of the vaccine at six to eight and two to four weeks before expected farrowing or left unvaccinated as controls. All the piglets were challenged intranasally with B bronchiseptica when three to seven days old and with P multocida three to four days later. Pigs born to the vaccinated sows performed significantly better than pigs born to the control sows when judged on growth, average daily weight gain and snout scores. The challenge organisms were reisolated more frequently from the control pigs than from the pigs in the vaccinated group. The vaccinated sows and their progeny developed high titres of antibodies against B bronchiseptica and P multocida toxin.     

Immunity to canine adenovirus respiratory disease: a comparison of attenuated CAV-1 and CAV-2 vaccines

Four litters of puppies were divided into three groups. One group was vaccinated with a live CAV-1 vaccine and another with a live CAV-2 vaccine. Throat swabs were collected from two dogs in each of these groups to monitor the possible excretion of vaccine virus, but none was found. Both groups, together with the third group of unvaccinated controls, were challenged 17 days later with an aerosol of virulent CAV-2. One dog from each group was killed on the third, fourth, seventh, ninth, 11th and 14th days after challenge. The unvaccinated dogs developed a clinical disease characterised by anorexia, dullness, coughing and tachypnoea. The lungs were consolidated and histological examination revealed the main lesion to be a severe necrotising bronchiolitis. Large amounts of virus were present in the respiratory tissues of these dogs and high titres of virus were isolated from throat swabs. In contrast, both groups of vaccinated dogs remained clinically almost normal with minimal lesions, present for a much shorter period of time. Virus was found on day 4 in the respiratory tissues of one dog vaccinated with CAV-1 but the other vaccinated animals contained little or no virus. In general, the degree of protection afforded by CAV-1 vaccine seemed similar to that provided by CAV-2 vaccine.     

Comparative efficacy of an injectable vaccine and an intranasal vaccine in stimulating Bordetella bronchiseptica-reactive antibody responses in seropositive dogs

OBJECTIVE: To compare antibody responses to intranasal and SC Bordetella bronchiseptica vaccines in seropositive dogs. DESIGN: Randomized controlled study. ANIMALS: 40 young adult Beagles vaccinated against B bronchiseptica. PROCEDURE: Dogs were randomly assigned to 1 of 4 groups (intranasal vaccine, SC vaccine, intranasal and SC vaccines, no vaccine) and vaccinated on day 0. Serum and salivary B bronchiseptica-reactive antibody responses were measured on days 0 through 7, 10, 14, 21, and 28. RESULTS: Dogs that were vaccinated with the SC vaccine, alone or in combination with the intranasal vaccine, had a significant increase in serum concentration of B bronchiseptica-reactive IgG beginning on day 5 and persisting through day 28. Dogs that were vaccinated with the intranasal vaccine alone had a significant increase in serum concentration of B bronchiseptica-reactive IgG beginning on day 10 and persisting through day 28, but serum IgG concentration in these dogs was significantly less than concentration in dogs that received the SC vaccine. Neither vaccine had a demonstrable effect on salivary concentrations of B bronchiseptica-reactive IgA or IgG. On day 10, all vaccinated groups had significantly higher serum IgA concentrations than did unvaccinated control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the SC B bronchiseptica vaccine may be used to stimulate antibody responses in seropositive dogs. There was no apparent benefit to administering these vaccines simultaneously. Intranasal vaccines may not be effective for booster vaccination of dogs previously exposed to or immunized against B bronchiseptica. Dogs should be vaccinated at least 5 days prior to exposure to B bronchiseptica.     

Canine parainfluenza-Bordetella bronchiseptica vaccine immunogenicity

The immunogenicity and safety of 3 serials of a canine parainfluenza (CPI) virus-Bordetella bronchiseptica vaccine was evaluated. Each serial was used to vaccinate 10 dogs with single doses given intranasally. The 30 vaccinated and 10 nonvaccinated controls dogs were challenge exposed with aerosols of virulent CPI virus and B bronchiseptica at 18 days and at 21 days, respectively, after vaccination. After challenge exposure, none of the 30 vaccinated dogs had clinical signs of disease; however, 9 of the 10 nonvaccinated dogs developed coughing problems. The CPI virus was isolated from nasal swab specimens obtained from nonvaccinated dogs on an average of 5.1 days after challenge exposure, but was not isolated from any of the specimens obtained from the vaccinated dogs. Bordetella bronchiseptica was isolated from nasal swab specimens obtained from both vaccinated and nonvaccinated dogs up to 18 days after challenge exposure. The erythrocyte sedimentation rates and total leukocyte counts for control dogs were generally increased, in contrast to those for the vaccinated groups. Dogs showed a primary serologic response to CPI virus and B bronchiseptica after vaccination and an anamnestic response to the bacterium after challenge exposure. Adverse local or systemic reactions attributable to the bivalent vaccine were not observed in the vaccinated dogs.     

Prior infection with Bordetella bronchiseptica increases nasal colonization by Haemophilus parasuis in swine

The objective of this study was to determine whether Bordetella bronchiseptica would predispose to colonization or disease with Haemophilus parasuis. Three experiments were completed. In the first experiment, three groups of pigs (10 pigs/group) were inoculated intranasally with either B. bronchiseptica, H. parasuis, or with B. bronchiseptica followed by H. parasuis 1 week later. A fourth group of 10 pigs served as a non-infected control group. The second experiment was like the first, except that there were only five pigs per experimental group. The third experiment consisted of only two groups (10 pigs/group), one of which was inoculated intranasally with H. parasuis, whereas the other was inoculated with B. bronchiseptica followed by H. parasuis 1 week later. Pigs were necropsied 1-2 weeks after inoculation with H. parasuis. Mean nasal colonization by H. parasuis was significantly higher in the coinfected groups compared to the groups infected with H. parasuis alone. Pneumonia was present in 9/25 pigs coinfected with B. bronchiseptica and H. parasuis, 5/25 pigs infected with H. parasuis alone, 1/15 pigs infected with B. bronchiseptica alone, and in none of the pigs in the non-inoculated groups. Thus, B. bronchiseptica increased colonization of the upper respiratory tract with H. parasuis.     

Canine infectious tracheobronchitis: effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough)

A modified-live intranasal (IN) canine parainfluenza (CPI)-virus Bordetella bronchiseptica vaccine was evaluated in dogs for efficacy against laboratory-induced canine infectious tracheobronchitis. The comparative efficacies of IN and parenteral administrations of the CPI virus fraction were also evaluated. The frequency and duration of clinical tracheobronchitis, blood serum agglutination titer, humoral antibody response, and duration of CPI virus and B bronchiseptica shedding were measured. Group A dogs were vaccinated subcutaneously or IM with an experimental CPI vaccine and challenge exposed with CPI virus. Group B dogs were vaccinated IN with avirulent CPI virus-B bronchiseptica live antigens and challenge exposed with virulent CPI virus and virulent B bronchiseptica. The IN vaccination (group B) significantly reduced (P less than or equal to 0.001) the occurrence of clinical tracheobronchitis by 96%. The combined challenge exposure of virulent CPI and virulent B bronchiseptica produced a synergistic enhancement of the clinical signs of kennel cough. The percentage of days after challenge exposure that virus shedding was detected for controls equaled 70% as compared with 50% and only 1% for parenterally and IN vaccinated dogs, respectively. Isolation of virulent B bronchiseptica microorganisms was reduced 89% in dogs vaccinated IN compared to controls. The geometric mean humoral antibody titers to CPI virus after 2 parenteral vaccinations and 1 IN vaccination were 1:43 and 1:34, respectively.     

Safety, efficacy and cross-protectivity of a live intranasal aerosol haemorrhagic septicaemia vaccine

The safety, efficacy and cross-protectivity of a live intranasal aerosol haemorrhagic septicaemia vaccine containing Pasteurella multocida serotype B:3,4 were tested in young cattle and buffaloes in Myanmar, where more than 1.5 million animals had been inoculated with this vaccine between 1989 and 1999. A recommended dose of 2 x 10(7) viable organisms was used for the efficacy test. The administration of 100 times the recommended dose to 50 cattle and 39 buffalo calves was innocuous. Seven months after they were vaccinated, three of three buffaloes were protected and 12 months after they were vaccinated, three of four buffaloes were protected against a subcutaneous challenge with serotype B:2 which killed three of three unvaccinated buffaloes. Twelve months after they were vaccinated, eight of eight cattle survived a serotype B:2 challenge, which killed four of four unvaccinated controls. The vaccinated cattle had developed serum antibodies detectable by the passive mouse protection test. Indirect haemagglutination tests on sera taken from cattle 10 days and five weeks after they were vaccinated showed high titres of antibodies. The serum of vaccinated cattle cross-protected passively immunised mice against infection with P. multocida serotypes E:2, F:3,4 and A:3,4.     

Canine bordetellosis: chemotherapy using a sulphadiazine-trimethoprim combination

Respiratory disease was induced in young dogs by exposure to an aerosol of Bordetella bronchiseptica. The affected dogs were then treated with a sulphadiazine-trimethoprim combination by daily subcutaneous injection for five days. There was marked improvement in the clinical, bacteriological and pathological features of the respiratory disease during and immediately after the treatment period but treated dogs relapsed a few days after chemotherapy was stopped. The use of a sulphadiazine-trimethoprim combination over a longer period of time may be of value in the treatment of dogs with respiratory disease associated with B bronchiseptica.     

Effects of intranasal inoculation of porcine reproductive and respiratory syndrome virus, Bordetella bronchiseptica, or a combination of both organisms in pigs

OBJECTIVE: To examine effects of co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Bordetella bronchiseptica in pigs. ANIMALS: Forty 3-week-old pigs. Procedure-30 pigs (10 pigs/group) were inoculated with PRRSV, B bronchiseptica, or both. Ten noninoculated pigs were control animals. RESULTS: Clinical signs, febrile response, and decreased weight gain were most severe in the group inoculated with both organisms. The PRRSV was isolated from all pigs in both groups inoculated with virus. All pigs in both groups that received PRRSV had gross and microscopic lesions consistent with interstitial pneumonia. Bordetella bronchiseptica was cultured from all pigs in both groups inoculated with that bacterium. Colonization of anatomic sites by B bronchiseptica was comparable between both groups. Pigs in the group that received only B bronchiseptica lacked gross or microscopic lung lesions, and B bronchiseptica was not isolated from lung tissue. In the group inoculated with B bronchiseptica and PRRSV, 3 of 5 pigs 10 days after inoculation and 5 of 5 pigs 21 days after inoculation had gross and microscopic lesions consistent with bacterial bronchopneumonia, and B bronchiseptica was isolated from the lungs of 7 of those 10 pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical disease was exacerbated in co-infected pigs, including an increased febrile response, decreased weight gain, and B bronchiseptica-induced pneumonia. Bordetella bronchiseptica and PRRSV may circulate in a herd and cause subclinical infections. Therefore, co-infection with these organisms may cause clinical respiratory tract disease and leave pigs more susceptible to subsequent infection with opportunistic bacteria.