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Infection and Immunity, May 2004, p. 3031-3037, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.3031-3037.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protection Elicited by a Double Leucine and Pantothenate Auxotroph of Mycobacterium tuberculosis in Guinea Pigs

Samantha L. Sampson,1 Christopher C. Dascher,2 Vasan K. Sambandamurthy,3 Robert G. Russell,4 William R. Jacobs Jr.,3 Barry R. Bloom,1 and Mary K. Hondalus1*

Department of Immunology and Infectious Diseases, Harvard School of Public Health,1 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115,2 Albert Einstein College of Medicine, Bronx, New York 10461,3 Department of Pathology, Lombardi Cancer Center, Georgetown University, Washington, D.C. 200574

Received 9 September 2003/ Returned for modification 4 December 2003/ Accepted 26 January 2004

We developed a live, fully attenuated Mycobacterium tuberculosis vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. The {Delta}leuD {Delta}panCD double auxotroph is fully attenuated in the SCID mouse model and highly immunogenic and protective in the extremely sensitive guinea pig tuberculosis model, reducing both bacterial burden and disease pathology.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. Phone: (617) 432-2940. Fax: (617) 432-3259. E-mail: mhondalu{at}hsph.harvard.edu.

Editor: A. D. O'Brien

Infection and Immunity, May 2004, p. 3031-3037, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.3031-3037.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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