Safety and efficacy testing of a novel multivalent bovine bacterial respiratory vaccine composed of five bacterins and two immunogens

Bovine bacterial respiratory diseases have been one of the most serious problems due to their high mortality and economic loss in calves. The vaccinations of bovine bacterial respiratory vaccines have been complex because of no multivalent vaccine. In this study, novel multivalent bovine bacterial respiratory vaccine (BRV) was developed and tested for its safety and efficacy. BRV was composed of two immunogens and five bacterins. These were leukotoxoid and bacterin of Mannheimia haemolytica type A, outer membrane protein and bacterin of Pasteurella multocida type A, and bacterins of Haemophilus somnus, Mycoplasma bovis, and Arcanobacterium pyogenes. ELISA antibody titers to five bacterial antigens in vaccinated guinea pigs increased, compared with those in unvaccinated ones. BRV was safe for calves and pregnant cattle in this study. In calves challenged with M. haemolytica and P. multocida, the average daily weight gain and antibody titers of vaccinated calves increased, and respiratory symptoms (P<0.05) and treatment frequency (P<0.01) of vaccinated calves significantly decreased, compared with those of unvaccinated calves. Interestingly, the antibody titers of M. haemolytica leukotoxoid and Mycoplasma bovis were closely related with the reduction of respiratory symptoms. BRV would be an ecomonical measure for the protection against bovine bacterial respiratory diseases.     

Serum and colostrum antibody to Pasteurella species in dairy cattle

A survey of antibody to Pasteurella haemolytica and P multocida, using a fluorometric immunoassay, was conducted on sera collected from 264 dairy cattle from 3 herds. Serum antibody titers to P haemolytica were 0 to 270 with low titers (less than 25) seen in 48.1% of the cows and heifers. Serum antibody titers to P multocida were 0 to 380 and the frequency of distribution of these titers were more even than for P haemolytica. Mean serum antibody titers to P haemolytica were significantly (P less than 0.005) higher in cattle from an open dairy herd when compared with those from 2 closed herds. Antibody titers to these organisms was determined in 7 colostrum samples. Pasteurella haemolytica antibody titers varied, depending on the whey separation technique used. Passive transfer of colostrum-derived antibody in 5 neonatal calves resulted in a maximum mean serum antibody titer at 20 hours after birth for P haemolytica and at 8 hours after birth for P multocida. Serum titers were higher overall for P multocida than for P haemolytica. Serum titers for P haemolytica declined rapidly. A significant (P less than 0.05) increase in antibody to P multocida was observed at 5 days of age.     

Maternally and naturally acquired antibodies to Mannheimia haemolytica and Pasteurella multocida in beef calves

The dynamics and duration of maternally derived antibodies as well as the onset of acquired immunity against Mannheimia haemolytica and Pasteurella multocida in range-pastured beef calves were investigated. Two groups of unvaccinated cattle were used in this study. Serum antibody responses were measured by enzyme-linked immunoassay for antibodies of the IgG1, IgG2 and IgM isotypes binding M. haemolytica whole cells (WC) or leukotoxin (LKT) and P. multocida outer membrane proteins (OMPs). Comparisons of mean antibody responses to M. haemolytica LKT and WC and P. multocida OMPs were made within each group. Maternally derived antibodies against M. haemolytica and P. multocida reached lowest levels at 30-90 days after birth. Calves began production of antibodies against M. haemolytica and P. multocida between 60 and 90 days of age in both groups. Based on the results of this study, in beef herds vaccinated against M. haemolytica and/or P. multocida, it may be best to vaccinate calves around 3 months of age. In contrast, beef calves from unvaccinated herds might benefit from vaccination at 4 months of age.     

Effect of vaccination with live or killed Pasteurella haemolytica on resistance to experimental bovine pneumonic pasteurellosis

Using 6- to 8-month-old beef calves, 3 experiments were conducted to compare the effect of vaccination with live or killed Pasteurella haemolytica on resistance to a transthoracic challenge exposure with the organism and to correlate serum antibody response with resistance. In each experiment, calves were vaccinated twice at 1-week intervals and were challenge exposed 21 days after the first inoculation. Lung lesions were evaluated by a system, such that higher scores indicated the more severe lesions. In each experiment, calves immunized with live P haemolytica had lower lesion scores than calves vaccinated with saline solution or bacterin. In 2 of the experiments, the differences were significant (P less than 0.05). In all experiments, calves vaccinated parenterally with a commercial P haemolytica/P multocida bacterin or with a formalin-killed P haemolytica bacterin had lesion scores that were not significantly different (P greater than 0.05) than for control calves vaccinated with saline solution. Live and killed bacterial preparations induced a significant serum antibody response to P haemolytica as measured by a quantitative fluorometric immunoassay. The antibody response to vaccination was not affected by preexisting titers to P haemolytica. Serum antibody titers were not consistently as high for calves vaccinated with bacterins as for calves vaccinated with live organisms. Although high antibody titers correlated with low lesion scores when calves vaccinated with saline solution or live organisms were analyzed collectively, there was not a significant correlation between the 2 variables when calves, vaccinated with saline solution or with bacterin, were analyzed collectively. These data indicate that, although bacterins may induce a detectable serum antibody response, they do not induce protection against transthoracic challenge exposure to P haemolytica.     

Effect of age at the time of vaccination on antibody titers and feedlot performance in beef calves

OBJECTIVE: To compare antibody responses, feedlot morbidity and mortality rates, feedlot performance, and carcass value for calves vaccinated with 1 of 2 vaccination strategies and for unvaccinated control calves. DESIGN: Randomized controlled clinical trial. ANIMALS: 451 beef steers and heifers. PROCEDURES: Calves were vaccinated with a modified-live infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus vaccine and Mannheimia haemolytica and Pasteurella multocida bacterin-toxoid at approximately 67 and 190 days of age (group 1; n = 151) or at approximately 167 and 190 days of age (group 2; 150) or were not vaccinated (control; 150). Serum antibody titers were measured at approximately 2, 67, 167, 190, and 232 days of age. Morbidity and mortality rates, feedlot performance, and carcass value were recorded for 361 calves shipped to feedlots. RESULTS: Percentages of calves seroconverting to IBRV, BVDV1, and BVDV2 were significantly higher for groups 1 and 2 than for the control group. Mean treatment costs were significantly lower for vaccinated than for control calves, and mean mortality rate was significantly higher for control calves than for group 1 calves. Feedlot performance and carcass value did not vary significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that vaccination of beef calves with a 5-antigen modified-live virus vaccine at 67 and 190 days of age was as effective in terms of immunologic responses as was vaccination at 167 and 190 days of age.     

Preliminary studies with a live streptomycin-dependent Pasteurella multocida and Pasteurella haemolytica vaccine for the prevention of bovine pneumonic pasteurellosis.

Twelve Pasteurella-free Holstein-Friesian calves were used in a study to test the efficacy of a live streptomycin-dependent Pasteurella multocida A:3 and streptomycin-dependent Pasteurella haemolytica A1 vaccine. The calves were inoculated intramuscularly twice at 14-day intervals with either the streptomycin-dependent vaccine, containing 1 X 10(6) colony forming units/mL P. multocida and 4 X 10(8) colony forming units/mL P. haemolytica, commercial bacterin, or phosphate buffered saline. Two weeks following the second vaccination, all calves were challenged by intranasal inoculation of 10(8) TCID50/4.0 mL infectious bovine rhinotracheitis virus followed three days later by intratracheal injection with 2.3 X 10(7) colony forming units/mL of a 16 hour culture of P. multocida A:3 and 2.6 X 10(8) colony forming units/mL of an 8 hour culture of P. haemolytica A1. Seven days after challenge with Pasteurella, calves were killed for collection of tissues at necropsy. Each calf was given a score based on macroscopic and microscopic lesions. The scores for the calves receiving live vaccines were significantly lower (p less than 0.025) than those for the controls. Also, the calves receiving live vaccines had a significant (p less than 0.05) increase in the level of serum antibody to P. haemolytica. The results of this preliminary study showed that the streptomycin-dependent vaccine offered better protection than the commercial bacterin against a virulent homologous challenge.     

Efficacy of a live Pasteurella multocida vaccine for the prevention of experimentally induced bovine pneumonic pasteurellosis

Seventeen Holstein-Friesian calves weighing an average of 139.8 +/- 13.5 (mean +/- standard deviation) kg were used in a study to determine the efficacy of a live vaccine containing of Pasteurella multocida A:3 and Pasteurella haemolytica A:1. Eleven calves received the vaccine by intramuscular injection in the right shoulder, whereas six calves received vaccine diluent and served as non-vaccinated controls. Fourteen days following vaccination (Day 15) all calves were inoculated deep intranasally with 3.6 X 10(7) TCID50 bovine herpes virus-1. On Day 16, calves were stressed by transports, and on Day 17 calves were challenged intratracheally with P. multocida A:3. On Day 22 calves were euthanized and necropsied, and tissues were collected for pathological and microbiological evaluations. Scores were assigned to each calf based on the severity of observed clinical signs. Macroscopic lung lesions were expressed as percentage of tissue involved relative to the total lung tissue of a calf. Plasma fibrinogen concentration, rectal temperature, serum antibody level, microscopic appearance of lung, and microbiologic results were also recorded for analyses. The control calves had significantly higher clinical-sign scores (P less than 0.05) and more severe gross lesions (P less than 0.05) than the vaccinated calves. Although the vaccinated calves had a slight increase of immunoglobulins M and G classes, the differences were not statistically significant (P greater than 0.05, P greater than 0.05). The results of the study indicate that the live Pasteurella vaccine is effective against experimental P. multocida infection in calves.     

Effects of various vaccination protocols on passive and active immunity to Pasteurella haemolytica and Haemophilus somnus in beef calves.

Two field trials were conducted in a beef cow herd in Saskatchewan to determine the effectiveness of a combined Pasteurella haemolytica and Haemophilus somnus vaccine in increasing passively and actively acquired antibodies in beef calves. Vaccination of dams at 4 and/or 7 weeks prepartum was associated with increased antibody titers to P. haemolytica and H. somnus in their serum (P < 0.05), colostrum (P < 0.05), and serum of their calves at 3 days and 1 month of age (P < 0.05). There was no significant (P > 0.05) difference in antibody titers in the colostrum and serum of calves from single or double vaccinated dams. Calves vaccinated at 1 and 2 months of age in the face of maternal antibodies to P. haemolytica and H. somnus had significantly (P < 0.05) higher antibodies to P. haemolytica and H. somnus at 4 and 6 months of age than did unvaccinated calves. Calves vaccinated at 3 and 4 months of age in the face of low levels of preexisting antibodies had significantly (P < 0.05) higher antibodies to P. haemolytica at 5 months of age and to H. somnus at 5 and 6 months of age than did unvaccinated calves. Calves vaccinated once at 4 months of age had significantly (P < 0.05) higher antibody titers to P. haemolytica and H. somnus at 4.5 months of age than did unvaccinated calves, but this difference was not apparent at 6 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vaccination studies against experimental bovine Pasteurella pneumonia.

Vaccination-challenge experiments were conducted in colostrum-deprived calves to evaluate the efficacy of Pasteurella bacterins and vaccines against experimental pneumonic pasteurellosis. Calves were vaccinated with formalin-killed bacterins and live vaccines, then challenge exposed intratracheally with P. haemolytica or P. multocida. Infectious bovine rhinotracheitis virus was inoculated intranasally three to four days prior to P. haemolytica challenge-exposure. All calves were examined for macroscopic and microscopic lesions after being found dead or following euthanasia four to seven days after challenge exposure with the bacterial pathogen. Clinical, hematological, and pathological responses to challenge exposure in aluminum hydroxide absorbed P. haemolytica and P. multocida bacterin-treated calves were consistent with the pneumonic lesions of pulmonary pasteurellosis in the control calves. An oil-adjuvanted P. haemolytica bacterin limited clinical and pathological responses in the affected calves whereas a P. multocida oil-adjuvanted bacterin did not. Both clinical and pathological responses to challenge exposure in calves vaccinated with live Pasteurella vaccines were less severe than those of the control calves. Vaccine effectiveness appeared to be dose dependent.     

Effects of dietary energy and starch concentrations for newly received feedlot calves: I. Growth performance and health

Crossbred calves (n = 572; initial BW = 186 +/- 27 kg) purchased from northern Texas, Arkansas, and southeast Oklahoma auction markets were delivered to the Willard Sparks Beef Research Center, Stillwater, OK, and used to study the effects of dietary energy and starch concentrations on performance and health of newly received feedlot calves during a 42-d receiving period. On arrival, calves were assigned randomly to one of two dietary energy levels (0.85 or 1.07 Mcal NEg/kg DM) and one of two dietary starch levels (34 or 48% of ME from starch) in a 2 x 2 factorial arrangement of treatments. Cattle were weighed and serum samples were collected on d 0, 7, 14, 28, and 42. Individual animal records of morbidity were kept for all cases of respiratory and other disease. Nasal swabs were collected from each morbid animal and cultured for upper-respiratory pathogens. There were no energy x starch level interactions for performance or health response variables. Daily gain (1.14 kg/d) and gain efficiency (ADG:DMI = 0.179) were not affected by increasing dietary energy or starch concentrations. Calves fed low-energy diets consumed (P < 0.05) more DM. No difference (P = 0.54) was detected in morbidity for calves fed high-energy (62.4% calves treated) compared with low-energy (65.8% calves treated) diets; however, calves fed the high-starch diets had numerically (P = 0.11) greater morbidity than calves fed low-starch diets (68.8 vs. 59.4% calves treated, respectively). There were no energy or starch effects on Mannheimia haemolytica or Pasteurella multocida antibody titers; however, day effects (P < 0.02) occurred. On d 7, 14, and 28, calves had antibody titers for P. multocida that were greater (P < 0.05) than titers on d 0. In addition, calves had greater antibody titers to M. haemolytica on d 7 and 14 than on d 0. Nasal swabs revealed that calves fed the high-energy diets tended (P = 0.06) to have a lower percentage of morbid calves with P. multocida during the first antimicrobial treatment and a lower percentage of Haemophilus somnus isolates during the first (P = 0.01) and second (P = 0.06) antimicrobial treatments than calves fed the low-energy diets. Although animal performance was not influenced, the present data suggest that feeding the high-energy diet decreased the percentage of P. multocida and H. somnus pathogens in calves that received one or more antimicrobial treatments.     

Efficacy of an inactivated respiratory syncytial virus vaccine in calves.

OBJECTIVE: To determine whether an inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from infection with virulent BRSV. DESIGN: Randomized controlled trial. ANIMALS: 27 nine-week-old calves seronegative for BRSV exposure. PROCEDURE: Group-1 calves (n = 9) were not vaccinated. Group-2 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing a minimum immunizing dose of antigen. Group-3 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing an amount of antigen similar to that in a commercial vaccine. All calves were challenged with virulent BRSV on day 42. Clinical signs and immune responses were monitored for 8 days after challenge. Calves were euthanatized on day 50, and lungs were examined for lesions. RESULTS: Vaccination elicited increases in BRSV-specific IgG and virus neutralizing antibody titers and in production of interferon-gamma. Virus neutralizing antibody titers were consistently less than IgG titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, whereas vaccinated calves had less severe signs of clinical disease and less extensive pulmonary lesions. The percentage of vaccinated calves that shed virus in nasal secretions was significantly lower than the percentage of control calves that did, and peak viral titer was lower for vaccinated than for control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus and decreased the severity of pulmonary lesions. Efficacy was similar to that reported for modified-live BRSV vaccines.     

Vaccination of neonatal colostrum-deprived calves against Pasteurella haemolytica A1.

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.     

In vitro lymphocyte proliferative responses and gamma-interferon production as measures of cell-mediated immunity of cattle exposed to Pasteurella haemolytica.

Cell-mediated immune mechanisms may play a role in the pathogenesis and prevention of pneumonia in cattle caused by Pasteurella haemolytica serotype A1. To determine the circumstances required to stimulate and identify cell-mediated immune responses, calves were vaccinated with a commercial P. haemolytica bacterin or a live commercial P. haemolytica vaccine, or were infected intratracheally with virulent P. haemolytica. All calves were challenge-exposed intratracheally with P. haemolytica 31 d after vaccination or prior infection. Peripheral blood mononuclear cells and mediastinal and superficial cervical lymph node cells were stimulated with antigens prepared from P. haemolytica to evaluate in vitro proliferative responses and gamma-interferon production as measures of cell-mediated immunity. Strong proliferative responses and gamma-interferon production were detected in lymph node cells from calves vaccinated with the live vaccine and from infected calves, especially in response to stimulation with an outer membrane protein preparation from P. haemolytica. Greater proliferative responses and gamma-interferon production were associated with the lymph node nearer the site of bacterin administration (superficial cervical lymph node) or the site of infection (mediastinal lymph node), whereas greater proliferative responses and gamma-interferon production were associated with the more distant lymph node (mediastinal lymph node) in calves vaccinated with the live vaccine. Neither proliferative responses nor gamma-interferon production were detected in peripheral blood mononuclear cells from calves that were vaccinated for or infected with P. haemolytica. Antileukotoxin antibody titers were determined by a serum neutralization assay, and protection against pneumonic lesions was more closely correlated with antileukotoxin antibody responses than with lymphocyte proliferation or gamma-interferon responses.     

Evaluation of protection against virulent bovine viral diarrhea virus type 2 in calves that had maternal antibodies and were vaccinated with a modified-live vaccine

OBJECTIVE: To evaluate the efficacy of an adjuvanted modified-live bovine viral diarrhea virus (BVDV) vaccine against challenge with a virulent type 2 BVDV strain in calves with or without maternal antibodies against the virus. DESIGN: Challenge study. ANIMALS: 23 crossbred dairy calves. PROCEDURES: Calves were fed colostrum containing antibodies against BVDV or colostrum without anti-BVDV antibodies within 6 hours of birth and again 8 to 12 hours after the first feeding. Calves were vaccinated with a commercial modified-live virus combination vaccine or a sham vaccine at approximately 5 weeks of age and challenged with virulent type 2 BVDV 3.5 months after vaccination. Clinical signs of BVDV infection, development of viremia, and variation in WBC counts were recorded for 14 days after challenge exposure. RESULTS: Calves that received colostrum free of anti-BVDV antibodies and were vaccinated with the sham vaccine developed severe disease (4 of the 7 calves died or were euthanatized). Calves that received colostrum free of anti-BVDV antibodies and were vaccinated and calves that received colostrum with anti-BVDV antibodies and were vaccinated developed only mild or no clinical signs of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the modified-live virus vaccine induced a strong protective immune response in young calves, even when plasma concentrations of maternal antibody were high. In addition, all vaccinated calves were protected against viral shedding, whereas control calves vaccinated with the sham vaccine shed virus for an extended period of time.     

Induction of pulmonary antibodies to Pasteurella haemolytica following intraduodenal stimulation of the gut-associated lymphatic tissue in cattle.

The induction of pulmonary antibodies to a bacterial antigen following intraduodenal (D) stimulation of the gut-associated lymphatic tissue (GALT) was investigated. Six calves were divided into two groups of three calves each. The GALT-primed calves received an ID dose of live Pasteurella haemolytica A1 followed by a subcutaneous (SC) dose of killed P. haemolytica. The sham-primed calves received an ID dose of phosphate-buffered saline solution (PBSS) followed by a SC dose of killed bacteria. Serum and pulmonary lavage fluids were collected weekly from each calf and assayed for titers of leukotoxin neutralizing antibodies (LNA), as well as IgG and IgA (lavage fluids only) to P. haemolytica. The GALT-primed calves responded to the ID stimulation by bacteria with increased serum IgG. The sham-primed calves had no change in antibody titers following ID stimulation. The GALT-primed calves had increased serum IgG, lavage IgG and IgA and increased LNA titers in both lavage fluids and serum following the SC dose of killed bacteria. The sham-primed calves demonstrated only an increase in serum IgG following the SC inoculation. A challenge study to evaluate if antibodies induced by GALT stimulation could reduce pulmonary lesions was performed using six calves divided into two groups. One group received an ID dose of P. haemolytica followed two weeks later by a SC dose of killed P. haemolytica. The sham vaccinated calves received an ID dose of PBSS followed in two weeks by a SC dose of killed bacterin. Calves were challenged by an intrapulmonary dose of live P. haemolytica A1 eleven days after the SC inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The frequency, distribution and effects of antibodies, to seven putative respiratory pathogens, on respiratory disease and weight gain in feedlot calves in Ontario.

During 1983-85, 279 calves requiring treatment for bovine respiratory disease and 290 comparison (control) animals from 15 different groups of feedlot calves were bled on arrival and again at 28 days postarrival. Their sera were then analyzed for antibodies to seven putative respiratory pathogens. On arrival, the prevalences of indirect agglutination titers to Pasteurella haemolytica, P. haemolytica cytotoxin, Mycoplasma bovis and M. dispar were greater than 50%, the prevalence of titers to bovine virus diarrhea virus (BVDV) was approximately 40%, and the prevalences of titers to infectious bovine rhinotracheitis virus (IBRV), bovine respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) were all below 25%. Seroconversion during the first month after arrival occurred in more than half the calves to P. haemolytica cytotoxin, PIV3 and RSV. Seroconversion of agglutination titers to P. haemolytica, Mycoplasma and BVDV occurred in about 40% of calves, and seroconversion to IBRV was infrequent (less than 5%). Initial titers were negatively correlated to subsequent titer changes within organism. Initial titers, and titer changes between organisms were essentially independent. Light calves had an increased risk of being selected for treatment for respiratory disease. Seroconversion to P. haemolytica cytotoxin, RSV and BVDV were predictive of respiratory disease cases, explaining approximately 69% of all respiratory disease cases in the feedlots. It was not possible to accurately predict weight gain or relapse from the serological data.     

Vaccination of dairy calves with bovine adenovirus type 3

A field study was undertaken to determine the efficacy of vaccinating dairy calves with a killed bovine adenovirus type 3 (BA3) vaccine in a herd where pneumonia associated with BA3 infection had been a severe problem. Calves were first vaccinated when they were less than one week old; a second dose was given 10-14 days later. Efficacy of the vaccine was evaluated following natural exposure to the virus by comparing prevalence of pneumonia in control (n = 21) and vaccinated (n = 21) calves. Seroconversion to BA3 was shown in 9 of 12 control calves that developed pneumonia, 4 of these calves subsequently died as a result of the disease. Four additional control calves had a subclinical infection with the virus. All calves in the vaccinated group developed virus-neutralizing antibodies which averaged 1:20 eight weeks after the second vaccination. The serologic response to vaccination was not inhibited in calves possessing low levels of colostral antibodies. Two vaccinated calves developed pneumonia but they did not succumb to the disease. The prevalence of pneumonia in vaccinated calves was significantly reduced (P less than 0.05) when compared to control calves.     

Clinical study of the disease of calves associated with Mycoplasma bovis infection

Clinical, bacteriological and serological examination of 35 calves from the age of 5 to 26 days was performed in a Holstein-Friesian dairy herd endemically infected with Mycoplasma bovis. M. bovis was isolated from 48.6% of nasal swabs taken from the calves at the age of 5 days, and from 91.4% of the same calves at the age of 26 days, indicating the gradual spread of infection. The isolation rate of Pasteurella multocida did not change much, and varied from 28.6 to 25.7%. No P. haemolytica could be detected. In addition to M. bovis and P. multocida, the herd was also infected with different viruses (including bovine viral diarrhoea virus, infectious bovine rhinotracheitis virus, bovine adenoviruses, parainfluenza-3 virus, and bovine respiratory syncytial virus) as a large proportion of the sera of newborn calves contained colostral antibodies against these viruses. In most of the newborn calves severe clinical signs (fever, depression, inappetence, hyperventilation, dyspnoea, nasal discharge and coughing) due to M. bovis infection developed. The clinical signs appeared already on the fifth day of life, and their incidence was the highest at the age of 10 to 15 days. Three calves (8.6%) died as a result of severe serofibrinous pneumonia. The surviving calves showed very poor weight gain (ranging from 1.5 to 3.5 kg) during the first two weeks of life.     

The immune response to experimental Pasteurella haemolytica infection in calves

Four male dairy calves, ages 1-9 months, were inoculated intratracheally (IT), with log dilutions (1.5 X 10(3)-1.5 X 10(6)) of an isolate of P. haemolytica A-1. Doses of bacteria varied according to ages of the calves, older calves receiving the larger doses. All four calves became severely ill within 24 h after inoculation and antibiotic treatment was considered essential. Two months later the four calves remained healthy after IT injection of P. haemolytica, again given in log dilution (2.8 X 10(2)-2.8 X 10(5)). The control calf, given a dilution of only 28 viable P. haemolytica (plate count), developed severe respiratory infection 9 days post inoculation. Antibiotic treatment was given to this calf for 7 days, at which time recovery was evident. All five calves developed direct bacterial agglutination titers to P. haemolytica. Persistent leukocyte migration inhibition indexes of all calves were decreased by greater than or equal to 20% compared to their controls. Although the initial doses administered were low, the calves became ill. Most reports refer to massive doses necessary to produce primary disease and significant agglutination titers.