Monophosphoryl lipid A-induced immune enhancement of Brucella abortus salt-extractable protein and lipopolysaccharide vaccines in balb/c mice

Louisa B. Tabatabai From the USDA, Agricultural Research Service, National Animal Disease Center, PO Box 70, Ames, IA 50010.

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George W. Pugh Jr. From the USDA, Agricultural Research Service, National Animal Disease Center, PO Box 70, Ames, IA 50010.

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Mark G. Stevens From the USDA, Agricultural Research Service, National Animal Disease Center, PO Box 70, Ames, IA 50010.

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Marshall Phillips From the USDA, Agricultural Research Service, National Animal Disease Center, PO Box 70, Ames, IA 50010.

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Timothy J. McDonald From the USDA, Agricultural Research Service, National Animal Disease Center, PO Box 70, Ames, IA 50010.

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SUMMARY

A study was conducted to determine the effect of monophosphoryl lipid A (mpl) and trehalose dimycolate (tdm) as adjuvants on the protective responses in balb/c mice vaccinated with Brucella abortus salt-extractable protein (bcsp) or proteinase-K-treated B abortus lipopolysaccharide (pklps). Mice were vaccinated with different doses of bcsp or pklps given alone or in combination with mpl or tdm. Mice were challenge-exposed 4 weeks later with virulent B abortus strain 2308. Two weeks after challenge exposure, the number of B abortus colony-forming units (cfu) per spleen, spleen weights, and spleen cell interleukin 1 production were measured. Serum IgG and IgM concentrations specific for vaccinal immunogens were measured before and after challenge exposure with B abortus.

Spleen weights and mean B abortus cfu per vaccine group were significantly lower in bcsp- and pklps-vaccinated mice, compared with those of nonvaccinated control mice. Monophosphoryl lipid A enhanced the suppression of splenic infection when given with the bcsp vaccine, but not when given with the pklps vaccine. Trehalose dimycolate had no effect on mean cfu when given with bcsp, but incorporation of tdm resulted in a significant increase in mean cfu when given with pklps. Spleen weights in bcsp- or pklps-vaccinated mice were not different when these vaccines were combined with mpl or tdm. Because of the wide variation in the results, we could not conclude that vaccination with bcsp or pklps alone, or in combination with mpl altered spleen cell interleukin-1 production in B abortus-infected mice. Increased host protection as defined by decreased cfu could not be related consistently to increased bcsp- or pklps-specific serum IgG or IgM antibodies introduced by any of the vaccines. These results do not eliminate a role for antibodies in the protection observed.

SUMMARY

A study was conducted to determine the effect of monophosphoryl lipid A (mpl) and trehalose dimycolate (tdm) as adjuvants on the protective responses in balb/c mice vaccinated with Brucella abortus salt-extractable protein (bcsp) or proteinase-K-treated B abortus lipopolysaccharide (pklps). Mice were vaccinated with different doses of bcsp or pklps given alone or in combination with mpl or tdm. Mice were challenge-exposed 4 weeks later with virulent B abortus strain 2308. Two weeks after challenge exposure, the number of B abortus colony-forming units (cfu) per spleen, spleen weights, and spleen cell interleukin 1 production were measured. Serum IgG and IgM concentrations specific for vaccinal immunogens were measured before and after challenge exposure with B abortus.

Spleen weights and mean B abortus cfu per vaccine group were significantly lower in bcsp- and pklps-vaccinated mice, compared with those of nonvaccinated control mice. Monophosphoryl lipid A enhanced the suppression of splenic infection when given with the bcsp vaccine, but not when given with the pklps vaccine. Trehalose dimycolate had no effect on mean cfu when given with bcsp, but incorporation of tdm resulted in a significant increase in mean cfu when given with pklps. Spleen weights in bcsp- or pklps-vaccinated mice were not different when these vaccines were combined with mpl or tdm. Because of the wide variation in the results, we could not conclude that vaccination with bcsp or pklps alone, or in combination with mpl altered spleen cell interleukin-1 production in B abortus-infected mice. Increased host protection as defined by decreased cfu could not be related consistently to increased bcsp- or pklps-specific serum IgG or IgM antibodies introduced by any of the vaccines. These results do not eliminate a role for antibodies in the protection observed.

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