This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) will provide $278,390 to The Regents of the University of California, San Francisco (UCSF) to conduct research on determining the value of the ESAT-6 antigen in Mycobacterium tuberculosis (MTB) infection and vaccines.
The key objectives are to: 1) Determine whether CD4 T cell responses to ESAT-6 are beneficial, detrimental, or neutral in MTB infection; 2) Evaluate whether ESAT-6 is a "decoy antigen" that alters recognition of other MTB antigens; and 3) Test the hypothesis that ESAT-6 contributes to vaccine efficacy through mechanisms beyond serving as a T cell immunogen. The project will utilize a novel transgenic mouse model to dissociate the role of ESAT-6 as a T cell antigen from its function as a virulence factor for MTB. Findings from this research will guide antigen selection for new tuberculosis vaccines and either increase confidence in ESAT-6 as a valuable vaccine candidate or provide evidence that alternative antigens should be prioritized.