ESAT-6 subunit vaccination against Mycobacterium tuberculosis

The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patie nts as well as in various animal models. The purpose of our study was to ev aluate the potential of ESAT-6 in an experimental TB vaccine. We started ou t using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has b een demonstrated to be efficient for the induction of cellular immune respo nses and has been used successfully before as a delivery system for TB vacc ines. Here we demonstrate that, whereas immune responses to both short-term -culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore , we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong ad juvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination o f MPL and DDA elicited a strong ESAT-6-specific T-cell response and protect ive immunity comparable to that achieved with Mycobacterium bovis BCG.