Vaccination with the T cell antigen Mtb 8.4 protects against challenge with Mycobacterium tuberculosis

The development of an effective vaccine against Mycobacterium tuberculosis is a research area of intense interest. Mounting evidence suggests that pro tective immunity to M. tuberculosis relies on both MHC class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells. By purifying poly peptides present in the culture filtrate of M. tuberculosis and evaluating these molecules for their ability to stimulate PBMC from purified protein d erivative-positive healthy individuals, we previously identified a low-m.w. immunoreactive T cell Ag, Mtb 8.4, which elicited strong Th1 T cell respon ses in healthy purified protein derivative-positive human PBMC and in mice immunized with recombinant Mtb 8.4. Herein we report that Mtb 8.4-specific T cells can be detected in mice immunized with the current live attenuated vaccine, Mycobacterium bovis-bacillus Calmette-Guerin as well as in mice in fected i.v. with M. tuberculosis. More importantly, immunization of mice wi th either plasmid DNA encoding Mtb 8.4 or Mtb 8.4 recombinant protein formu lated with IFA elicited strong CD4(+) T cell and CD8(+) CTL responses and i nduced protection on challenge with virulent M. tuberculosis. Thus, these r esults suggest that Mtb 8.4 is a potential candidate for inclusion in a sub unit vaccine against TB.