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Infection and Immunity, May 2002, p. 2535-2543, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2535-2543.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Recombinant Ochrobactrum anthropi Expressing Brucella abortus Cu,Zn Superoxide Dismutase Protects Mice against B. abortus Infection Only after Switching of Immune Responses to Th1 Type

Yongqun He, Ramesh Vemulapalli, and Gerhardt G. Schurig^*

Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0342

Received 9 July 2001/ Returned for modification 24 September 2001/ Accepted 29 January 2002

The members of the genus Brucella are gram-negative, facultatively intracellular bacterial pathogens that cause brucellosis in many animal species and humans. Although live, attenuated vaccines are available to protect several animal species from the disease, there is no safe and effective vaccine for human use. Here we report that a bacterium that is closely related to Brucella species, Ochrobactrum anthropi, can be used as a vaccine vector for the delivery of Brucella antigens to mice, leading to the elicitation of protective immunity against brucellosis. Brucella abortus Cu,Zn superoxide dismutase (SOD), a protective Brucella antigen, was expressed in large amounts in O. anthropi strain 49237 by use of the broad-host-range plasmid pBBR1MCS. Neither O. anthropi strain 49237 nor the recombinant O. anthropi strain 49237SOD, expressing B. abortus Cu,Zn SOD, provided protection against virulent Brucella infection in mice. Analysis of immune responses indicated that strains 49237 and 49237SOD stimulated a mix of Th1 and Th2 type responses in the mice. After the immune response was switched to a Th1-biased response by addition of oligonucleotides containing unmethylated CpG motifs, both O. anthropi strain 49237 and the recombinant O. anthropi strain 49237SOD induced protection in mice. However, the protection conferred by strain 49237SOD was significantly better than that induced by the parental strain, 49237.

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* Corresponding author. Mailing address: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd., Blacksburg, VA 24061-0342. Phone: (540) 231-7172. Fax: (540) 231-5815. E-mail: gschurig{at}vt.edu.

Editor: R. N. Moore

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Infection and Immunity, May 2002, p. 2535-2543, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2535-2543.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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