Scientific Publications by FDA Staff

Infect Immun 2008 May;76(5):2249-55

Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection.

Wu Y, Woodworth JS, Shin DS, Morris S, Behar SM

Behar, SM (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith Bldg,Room 516C,1 Jimmy Fund Way, Boston, MA 02115 USA Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA US FDA, CBER, Lab Mycobacteriol Dis & Cellular Immunol, Bethesda, MD 20892 USA

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.