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  • Author or Editor: Fred M. Enright x
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SUMMARY

Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 × 104 virulent Brucella abortus, caused significant (P < 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P < 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P < 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P < 0.01) greater in B abortus -infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P < 0.01) diminished. The increase in numbers of B abortus in organs of irradiated mice that began after the third week coincided with recovery of the immune response and an increase in numbers of neutrophils and monocytes in the infected organs. The course of B abortus infection was not substantially altered during the first 11 days after inoculation in mice infected at the height of a profound monocytopenia and neutropenia induced by azathioprine, a drug that by itself failed to activate macrophages. We hypothesized that, in irradiated mice, a rapid radiation-induced activation of resident macrophages to a brucellacidal state was coupled with an absence of newly formed monocytes in which virulent strains of B abortus could establish persistent infection, and that as susceptible monocytes emerged in mice recovering from the effects of irradiation, chronic infection became established.

Free access
in American Journal of Veterinary Research

Summary

A model of bovine pneumonic pasteurellosis, using an indwelling bronchial catheter for inoculation and subsequent lavage of a single main stem bronchus of the lung, was evaluated in a preliminary efficacy trial of an experimental therapeutic compound. Inoculation of 107 Pasteurella haemolytica organisms into the bronchus consistently induced a focal pneumonic lesion with typical morphology of pneumonic pasteurellosis in the left or right caudal lung lobe. The experimental treatment caused significant (P < 0.05) reduction in lung lesion volume, compared with that of a saline-treated control. It also caused significant (P < 0.05) reduction in lavage fluid bacterial counts at 48 hours after inoculation, compared with counts in the controls. The inflammatory cell count and the percentage of neutrophils increased markedly in lavage fluids 8 hours after inoculation, but differences were not detected between treatments. Significant differences between treatments were not found in clinical signs, rectal temperature, or histologic changes. This model appears to be a sensitive indicator of treatment efficacy and has the advantage over previous models of pneumonic pasteurellosis of allowing sequential monitoring of the primary lesion site.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate stable rough mutants derived from Brucella melitensis 16M and B suis 2579 (biovar 4) as vaccines against homologous and heterologous Brucella spp in the BALB/c mouse model.

Design, Animals, and Procedure

Rough mutants VTRM1 and VTRS1 were obtained from B melitensis 16M and B suis 2579, respectively, by allelic exchange of the rfbU gene encoding mannosyltransferase with a Tn5-disrupted rfbU gene. Mice were vaccinated with VTRM1 or VTRS1 and challenge exposed 8 weeks later.

Results

VTRM1 and VTRS1 replicated extensively in the spleen during the first 3 weeks of infection, then decreased rapidly. Antibodies specific for the O polysaccharide were not detected in sera of mice inoculated with either rough strain. Vaccination with VTRM1 or VTRS1 induced protection against virulent strains of B abortus (2308), B melitensis (16M), B suis biovar 1 (750), and B suis biovar 4 (2579). VTRM1 also protected against B ovis (PA) and against 4 field isolates of B abortus from bison or elk. VTRS1 conferred protection against 4 field isolates of B suis biovar 4 from reindeer. Vaccines prepared from live VTRM1 or VTRS1 provided significantly greater protection than that afforded by vaccines of killed cells in QS- 21 adjuvant. Vaccination with VTRM1 containing VTRS1 gave minimal protection against the antigenically unrelated Listeria monocytogenes, thus demonstrating the immunologic specificity of protection against Brucella spp.

Conclusions and Clinical Relevance

Results encourage evaluation, in primary host species, of VTRM1 and VTRS1, along with RB51, as alternative vaccines to strain 19, Rev 1, or other smooth phase vaccines. (Am J Vet Res 1996; 57:677–683)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To develop a novel oral vaccine delivery system for swine, using the rough vaccine strain of Brucella abortus.

Animals—56 crossbred pigs from a brucellosis-free facility.

Procedure—In 3 separate experiments, pigs were orally vaccinated with doses of 1 × 109 to > 1 × 1011 CFU of strain RB51 vaccine. The vaccine was placed directly on the normal corn ration, placed inside a whole pecan, or mixed with cracked pecans and corn.

Results—Oral vaccination of pigs with vaccine strain RB51 resulted in a humoral immune response to strain RB51 and short-term colonization of the regional lymph nodes.

Conclusions and Clinical Relevance—A viscous liquid such as Karo corn syrup in association with pecans that scarify the oral mucosa are necessary when placing the live vaccine directly onto corn or other food rations. Doses of > 1 × 1011 CFU of RB51 organisms/pig in this mixture ensures 100% colonization of regional lymph nodes via the oral route. This method may allow an efficient and economical means to vaccinate feral swine for brucellosis. (Am J Vet Res 2001;62:1328–1331)

Full access
in American Journal of Veterinary Research

Abstract

Objectives

To determine efficacy of orally administered Brucella abortus vaccine strain RB51 against virulent B abortus challenge exposure in cattle as a model for vaccination of wild ungulates.

Animals

20 mixed-breed beef cattle obtained from a brucellosis-free herd.

Procedure

Sexually mature, Brucella-negative beef heifers were vaccinated by mixing > 1010 viable RB51 organisms or diluent with their feed. Heifers were fed individually and consumed their entire ration. Each heifer received approximately 3×1010 colony-forming units (CFU). Six weeks after oral vaccination, heifers were pasture-bred to brucellosis-free bulls. At approximately 186 days' gestation, heifers were challenge exposed conjunctively with 107 CFU of virulent B abortus strain 2308.

Results

Vaccination with the rough variant of B abortus RB51 did not stimulate antibodies against the O-polysaccharide (OPS) of B abortus. After challenge exposure and parturition, strain 2308 was recovered from 80% of controls and only 20% of vaccinates. Only 30% of the vaccinates delivered dead, premature, or weak calves, whereas 70% of the controls had dead or weak calves.

Conclusions

Cattle vaccinated orally with the rough variant of B abortus strain RB51 develop significant (P< 0.05) protection against abortion and colonization and do not produce OPS-specific antibodies.

Clinical Relevance

Results encourage further investigation into use of strain RB51 to vaccinate wild ungulates (elk and bison) orally. (Am J Vet Res1998; 59:1575-1578)Vol 59, No. 12, December 1998

Free access
in American Journal of Veterinary Research