Aerosol vaccination against Newcastle disease. I. Studies on particle size.

Studies revealed that the majority of particles emitted by three different aerosol generators were in the size ranges of 0.5-1 and 1-3 mum. In general, the smaller the aperture setting, the larger the total number of particles. The difference between the generators in number of particles emitted were not significant enough to produce appreciable difference in antibody titers obtained from vaccinated chickens. Antibody titers were higher in birds vaccinated with the LaSota strain of Newcastle disease virus than in birds vaccinated with the B-1 strain, although protection against challenge was approximately similar. Aerosol challenge was found as effective as intramuscular challenge.     

Bovine herpesvirus-1 vaccination against experimental bovine herpesvirus-1 and Pasteurella haemolytica respiratory tract infection: onset of protection

The onset of protection offered by intranasal vaccination with attenuated bovine herpesvirus-1 (BHV-1) was studied in 18 calves given a virulent BHV-1 aerosol challenge inoculum and an aerosol challenge exposure to Pasteurella haemolytica. Calves challenge exposed with virus 3, 7, 11, 15, or 19 days after vaccination and challenge exposed 4 days later with Pasteurella haemolytica did not develop viral-bacterial pneumonia, whereas 2 of 3 control calves died of fibrinous bronchopneumonia 40 and 60 hours after the bacterial aerosol and the 3rd control calf had similar lesions. All vaccinated and control calves had detectable amounts of interferon at the time of viral challenge exposure. Protection was observed before detection of neutralizing antibodies to BHV-1 in nasal secretions or in serum. Protection was therefore present from day 3 through day 19 after vaccination, but the mechanism could not be explained completely by neutralizing antibody or interferon.     

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.     

Effects of tilmicosin treatment on Pasteurella haemolytica organisms in nasal secretion specimens of calves with respiratory tract disease

OBJECTIVE: To determine the effect of tilmicosin treatment on number of Pasteurella haemolytica (PH) organisms in nasal secretion specimens of calves with respiratory tract disease. ANIMALS: 206 British mixed-breed beef calves, 2 to 5 months old. PROCEDURE: In 2 separate studies of outbreaks, calves (study 1, n = 101; study 2, n = 105) that developed respiratory tract disease after transport to a feedlot were treated with tilmicosin. Nasal secretion specimens were examined for PH organisms to determine the status of colonization. RESULTS: In both studies, PH serotypes A1 and A6 were isolated. In study 1, tilmicosin treatment eliminated or markedly reduced the number of PH organisms in calves on days 1, 4, and 5 after treatment. In study 2, tilmicosin treatment eliminated PH organisms in calves on days 1, 2, 5, and 6 after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, tilmicosin treatment increased the number of culture-positive calves that became culture-negative and decreased the number of culture-negative calves that became culture-positive for up to 6 days after treatment. Tilmicosin treatment decreased the number of PH organisms in nasal secretion specimens, which indicated that fewer PH organisms were available to infect the lungs or to infect other calves. By reducing colonization, prophylactic use of tilmicosin before transport or at the time of arrival at a feedlot is likely to reduce the incidence of acute respiratory tract disease in calves for the initial several days after arrival, which is the period when they are most susceptible to infectious organisms.     

Mannheimia haemolytica and bovine respiratory disease

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.     

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.     

Colonization of the tonsils of calves with Pasteurella haemolytica.

Tonsils of 10 calves were inoculated with Pasteurella haemolytica (PH) and the degree of colonization was followed by collecting sequential tonsil. wash specimens. Tonsils were colonized for at least 3 weeks after instillation of PH into the tonsillar sinus. Calves with colonized tonsils responded with serum and nasal secretion antibody responses to PH and to leukotoxin. Pasteurella haemolytica was detected in nasal mucus specimens of 2 calves during the week after inoculation of the tonsils, but all other specimens were culture-negative. Infectious bovine rhinotracheitis virus-induced respiratory tract disease 25 days later did not elicit a population increase of PH in the tonsils, and did not elicit shedding of PH in nasal mucus.     

Respiratory disease in calves produced with aerosols of parainfluenza-3 virus and Pasteurella haemolytica.

In four experiments, 22 calves were exposed to aerosols of parainfluenza-3 virus, followed by Pasteurella haemolytica at intervals of three to 13 days. The purpose of each experiment was to study viral-bacterial interactions in the respiratory tracts. Two experiments, in which the viral aerosols were diluted by the addition of air, produced sporadic temperature elevations while two experiments with undiluted viral aerosols produced consistent temperature elevations. Diluted viral aerosols produced lobular sized lesions in the lungs and hemagglutinating inhibition antibodies in sera, whilst undiluted aerosols produced a synergistic effect in the form of purulent pneumonia in ten of 14 calves when the interval between viral and bacterial aerosols was from three to ten days. Histopathological changes attributable to the virus only were seen in all experiments, and the histopathological changes due to mixed infection of parainfluenza-3 virus and P. haemolytica are described in detail. This is the first report of extensive purulent pneumonia in calves after parainfluenza-3 virus and P. haemolytica exposure. This was achieved using much smaller inocula than in experiments previously reported.     

Vaccination of calves with leukotoxic culture supernatant from Pasteurella haemolytica.

In three experiments subcutaneous vaccination of calves with adjuvanted bacteria-free leukotoxic culture supernatant from log phase cultures of Pasteurella haemolytica A1 (toxin 1) was shown to induce some protection against intrabronchial challenge with live P. haemolytica A1. This toxin 1 vaccine was as effective as a whole cell bacterin in stimulating agglutinating antibody to P. haemolytica. Induction of leukotoxin neutralizing activity was variable; in some cases vaccination only primed the animal to produce an anamnestic response after challenge, whereas in other instances antitoxic activity increased in response to immunization. Two doses of vaccine were shown to be more effective than a single immunization. Vaccination with leukotoxic culture supernatant from the nonpathogenic P. haemolytica serotype 11 was as effective as vaccination with toxin 1 in stimulating antitoxic activity but was not protective. This implies that both serospecific agglutinating activity and an antitoxic response are needed for immunity.