Correlation of macrophage migration-inhibition factor and protection from challenge exposure in calves vaccinated with Salmonella typhimurium.

Migration of bovine macrophages under agarose was used to assess cellular immunity in 7 nonvaccinated calves and 9 calves vaccinated with Salmonella typhimurium. The 9 vaccinated calves were allotted to 4 groups. Group I calves were vaccinated twice orally with small doses of virulent S typhimurium; group II calves were vaccinated twice orally with genetically altered aromatic-dependent (aro-) S typhimurium SL3261; group III calves were vaccinated twice IM with small doses of virulent S typhimurium; and group IV calves were vaccinated twice IM with aro- S typhimurium SL1479. Samples of blood were obtained from these calves at 2 weeks after the 2nd vaccinal dose was given, and lymphocytes were harvested, using lymphocyte separation medium. Lymphocytes in serum-free medium were then incubated with S typhimurim antigen for 48 hours. Lymphocytes were then transferred to antigen-free medium and incubated for 48 hours, and the supernatant was assayed for the migration-inhibition factor (MIF). Lymphocyte supernatant was assayed for MIF by incubating it for 48 hours with 2.0 X 10(4) alveolar macrophages in agar wells. The macrophage migration distance was measured and compared with control values. Macrophage migration was inhibited in the presence of supernatant of lymphocytes from vaccinated calves that had been incubated with antigen, indicating the presence of the MIF in the supernatant. Migration distances, as a percentage of control, were 33% for group I calves (oral vaccination, virulent vaccinal organism), 60% for group II calves (oral vaccination, aro- vaccinal organism), 41% for group III (IM vaccination, virulent organism), and 25% for group IV (IM vaccination, aro- vaccinal organism).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of cutaneous delayed hypersensitivity to protection from challenge exposure with Salmonella typhimurium in calves.

The purpose of this investigation was to relate cutaneous delayed hypersensitivity reactions to the degree of immunity induced in calves given a live virulent or a modified-live strain of Salmonella typhimurium. Calves were placed into 1 of 5 groups on the basis of the vaccinal strain given and route of the vaccination: (I) nonvaccinated controls, (II) vaccinated twice by IM inoculation with small doses of the live virulent strain, (III) vaccinated (IM) twice with the modified-live strain, (IV) vaccinated (orally) twice with the modified-live strains, and (V) vaccinated (IM, and then orally) twice with the modified-live strain. Skin testing was performed by intradermal injection of fragmented S typhimurium as antigen. Double skin fold thickness and visual assessments were recorded at 3, 6, 24, 48, and 72 hours after antigen was administered. Biopsy samples for histopathologic evaluation were obtained. After vaccination and skin testing were complete, calves were orally challenge exposed with 1.5 X 10(11) virulent S typhimurium. Cutaneous delayed-type hypersensitivity reactions (48 hours) were observed in all except controls (group I) and 2 of 3 calves vaccinated orally with the modified-live vaccine strain (group IV). Significant correlations between positive skin tests and protection from challenge exposure were observed except in group V calves, in which positive skin test results were seen, but adequacy of the immunity (or survival after challenge exposure) was inconsistent.

Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves.

Strains of Salmonella sp with complete nonreverting aromatic biosynthesis (aro) defects are expected to be nonvirulent, in respect to invasive infection, because they need the aromatic metabolites paraaminobenzoate (for making folate) and dihydroxybenzoate (for making enterochelin) which are not available in host tissues. Derivatives with transposon-generated complete nonreverting aro-defects were prepared from 3 mouse-virulent strains of S typhimurium, namely, FIRN, WRAY, and UCD. The latter 2 parent strains originally were isolated from calves and are known to be calf-virulent. The resultant aromatic-dependent (aro-) strains were used to vaccinate 27 calves (2 to 3 weeks old), usually giving 2 doses by the IM route (10(9) bacteria) or orally (1.5 X 10(11)). Vaccination did not cause severe ill effects in any calf. Thus aro- defects cause loss of virulence for calves, as previously shown for mice. Vaccinated and control calves were challenge exposed, usually at 5 weeks of age, by feeding 1.5 X 10(11) cells of 1 of 2 calf-virulent S typhimurium strains, either UCD 108-11 or SL1323. Of the 16 challenge-exposed control calves, all became anorectic and depressed (CNS), and 15 had diarrhea. Fourteen of the 16 died; all tested tissues were bacteriologically culture-positive for Salmonella at necropsy. Vaccination with the live UCD aro- vaccine strain, SL1479 by either of 2 schedules (IM or orally) appeared effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunization of calves against salmonellosis.

Fifty-six normal colostrum-fed Holstein-Friesian and Holstein-Friesian X Angus crossbred calves ranging in age from 3 to 9 weeks were divided into 4 vaccinated groups and 1 nonvaccinated (control) group. Group I consisted of 10 calves vaccinated 2 or 3 times subcutaneously with formalin-killed Salmonella dublin-S typhimurium bacterin with added adjuvant. Group II consisted of 4 calves vaccinated orally with formalin-killed S typhimurium daily for 21 days. Group III consisted of 17 calves given colostrum from dams which had been vaccinated twice subcutaneously with a formalin-killed S dublin-S typhimurium bacterin with added adjuvant. Group IV consisted of 8 calves orally given small doses of live virulent S typhimurium twice. Seventeen calves served as nonvaccinated controls. One to 2 weeks after the final vaccine dose (or at 3-weeks of age for group III), all calves were orally challenge exposed with virulent S typhimurium. Oral challenge dose levels ranged from 1.5 X 10(9) viable organisms to 1.5 X 10(11) viable organisms. Mortality following oral challenge exposure was 11 of 17 controls, 6 of 10 group I calves (ns), 2 of 4 group II calves (ns), 11 of 17 group III calves (ns), and 1 of 8 group IV calves (p = 0.001). Twenty calves, 4 from group I, 8 from group III, and 8 from the control group, given 1.5 X 10(11) challenge organisms (the largest challenge, inoculum) died, whereas only 1 of 6 calves in group IV given this dose died. Group II calves were not given the 1.5 X 10(11) challenge dose. Under the conditions of this experiment, bacterins given parenterally or orally to calves or given parenterally to the dams of calves did not decrease morbidity and mortality, whereas small numbers of live organisms given orally to calves were effective in lessening morbidity and mortality following oral challenge exposure with virulent S typhimurium.

Bovine salmonellosis: experimental production and characterization of the disease in calves, using oral challenge with Salmonella typhimurium.

A highly virulent strain of Salmonella tyhimurium was given orally to produce disease experimentally in 21 normal colostrum-fed calves 3 to 9 weeks old. The challenge inoculum varied from 10(4) to 10(11) organisms. The disease was characterized by fever, depressed attitude, and decreased appetite. Many calves given larger challenge dose levels also had diarrheic feces containing mucus, fibrin, and blood. Fecal cultures were positive for salmonella. Septicemia occurred in some calves (9 of 15 calves cultured were positive). Eleven calves died and 10 calves survived challenge exposure. Survival was inversely related to the size of the challenge inoculum and directly related (although to a lesser degree) to age of the calf. White blood cell total and differential counts were variable. Both neutropenia and neutrophilia were observed. Plasma proteins decreased markedly in calves with diarrhea, probably indicating fecal protein loss. Fibrinogen increased during the acute stages of diarrhea.