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Vaccine-Elicited 10-Kilodalton Culture Filtrate Protein-Specific CD8⁺ T Cells Are Sufficient To Mediate Protection against Mycobacterium tuberculosis Infection

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115,¹ Laboratory of Mycobacterial Diseases and Cellular Immunology, FDA/CBER, Bethesda, Maryland 20892²

Received 7 January 2008/ Returned for modification 23 February 2008/ Accepted 28 February 2008

The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are frequently recognized by T cells from infected people. The genes encoding these proteins have been deleted from the genome of the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG), and it is hypothesized that these proteins are important targets of protective immunity. Indeed, vaccination with ESAT-6 elicits protective CD4⁺ T cells in C57BL/6 mice. We have previously shown that M. tuberculosis infection of C3H mice elicits CFP-10-specific CD8⁺ and CD4⁺ T cells. Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a specific T-cell response only to the H-2K^k-restricted epitope CFP-10_32-39. These CFP-10_32-39-specific CD8⁺ cells undergo a rapid expansion and accumulate in the lung following challenge of immunized mice with aerosolized M. tuberculosis. Protective immunity is induced by CFP-10 DNA vaccination as measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge with M. tuberculosis. These data demonstrate that CFP-10 is a protective antigen and that CFP-10_32-39-specific CD8⁺ T cells elicited by vaccination are sufficient to mediate protection against tuberculosis.

Published ahead of print on 10 March 2008.

Editor: J. L. Flynn