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Infection and Immunity, July 2004, p. 4031-4039, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.4031-4039.2004

Oral Vaccination with Brucella melitensis WR201 Protects Mice against Intranasal Challenge with Virulent Brucella melitensis 16M

Mina J. Izadjoo,^1* Apurba K. Bhattacharjee,² Chrysanthi M. Paranavitana,² Ted L. Hadfield,¹ and David L. Hoover²

Department of Infectious and Parasitic Diseases, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000,¹ Department of Bacterial Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-5100²

Received 8 December 2003/ Returned for modification 26 January 2004/ Accepted 26 March 2004

Human brucellosis can be acquired from infected animal tissues by ingestion, inhalation, or contamination of conjunctiva or traumatized skin by infected animal products. In addition, Brucella is recognized as a biowarfare threat agent. Although a vaccine to protect humans from natural or deliberate infection could be useful, vaccines presently used in animals are unsuitable for human use. We tested orally administered live, attenuated, purine auxotrophic B. melitensis WR201 bacteria for their ability to elicit cellular and humoral immune responses and to protect mice against intranasal challenge with B. melitensis 16M bacteria. Immunized mice made serum antibody to lipopolysaccharide and non-O-polysaccharide antigens. Splenocytes from immunized animals released interleukin-2 and gamma interferon when grown in cultures with Brucella antigens. Immunization led to protection from disseminated infection and enhanced clearance of the challenge inoculum from the lungs. Optimal protection required administration of live bacteria, was related to immunizing dose, and was enhanced by booster immunization. These results establish the usefulness of oral vaccination against respiratory challenge with virulent Brucella and suggest that WR201 should be further investigated as a vaccine to prevent human brucellosis.

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* Corresponding author. Mailing address: Department of Bacterial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910-5100. Phone: (301) 319-9495. Fax: (301) 319-9123. E-mail: mina.izadjoo{at}na.amedd.army.mil.

Editor: F. C. Fang

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Infection and Immunity, July 2004, p. 4031-4039, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.4031-4039.2004

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