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Infection and Immunity, October 2006, p. 5820-5825, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00331-06

Comparison of Protective Efficacy of Subcutaneous versus Intranasal Immunization of Mice with a Brucella melitensis Lipopolysaccharide Subunit Vaccine

Apurba K. Bhattacharjee,^1* Mina J. Izadjoo,² Wendell D. Zollinger,¹ Mikeljon P. Nikolich,¹ and David L. Hoover^1,

Department of Bacterial Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500,¹ Department of Environmental and Infectious Disease Sciences, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000²

Received 28 February 2006/ Returned for modification 10 May 2006/ Accepted 7 July 2006

Groups of mice were immunized either subcutaneously or intranasally with purified Brucella melitensis lipopolysaccharide (LPS) or with LPS as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (LPS-GBOMP). Control mice were inoculated with sterile saline. Two doses of vaccine were given 4 weeks apart. Mice were challenged intranasally with virulent B. melitensis strain 16M 4 weeks after the second dose of vaccine. Sera, spleens, lungs, and livers of mice were harvested 8 weeks after challenge. The bacterial loads in the organs were determined by culture on brucella agar plates. Protective efficacy was determined by comparing the clearance of bacteria from organs of immunized mice with the clearance of bacteria from organs of control mice. At 8 weeks postchallenge there was significant protection from disseminated infection of spleens and livers of mice intranasally immunized with either vaccine compared to infection of control mice (P < 0.01). There was no significant difference in clearance of bacteria from the lungs of immunized mice and control mice. However, mice immunized subcutaneously with either LPS or LPS-GBOMP vaccine showed significant protection against infection of the spleen (P < 0.001), liver (P < 0.001), and lungs (P < 0.05). These results show that intranasal immunization of mice with either vaccine provided significant protection against disseminated infection of the spleen and liver but subcutaneous immunization of mice with the vaccines conferred significant protection against infection of the spleen, liver, and lungs.

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* Corresponding author. Mailing address: Department of Bacterial Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. Phone: (301) 319-9657. Fax: (301) 319-9123. E-mail: Apurba.Bhattacharjee{at}us.army.mil.

Editor: D. L. Burns

Present address: Clinical Research Department, DVC LLC, 64 Thomas Johnson Drive, Frederick, MD 21702.

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Infection and Immunity, October 2006, p. 5820-5825, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00331-06

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