ESAT-6 subunit vaccination against Mycobacterium tuberculosis

Abstract

The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. 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 adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved with Mycobacterium bovis BCG.

FIG. 1

Evaluation of immune responses induced by TB subunit vaccines. Proliferative responses and IFN-γ release were measured 14 days postinfection (spleen cell cultures) or 3 weeks after vaccination (lymph node cell cultures) with either ST-CF–DDA, Ag85B–DDA, or ESAT-6–DDA. Cells are pooled from three to five mice per group. Each bar represents the mean of triplicate values. Error bars, standard errors of the means. This experiment was performed twice with similar results.