ESAT6-CFP10-Mtb32-HspX fusion protein (EC32H)

The ESAT6-CFP10-Mtb32-HspX fusion protein is a recombinant multi-stage subunit vaccine candidate designed to provide comprehensive protection against Mycobacterium tuberculosis (Mtb). This fusion construct integrates four immunodominant antigens: ESAT-6 and CFP-10, which are potent T-cell antigens secreted during the early stages of infection; Mtb32 (Rv0125), a serine protease associated with active bacterial replication; and HspX (Rv2031c), a heat shock protein predominantly expressed during the latent or persistent phase (Lu et al., 2015, Molecular Medicine Reports). By targeting multiple stages of the bacterial life cycle, the protein aims to prevent both initial infection and the reactivation of latent tuberculosis (Wu et al., 2021, Vaccine). It is typically administered with an adjuvant system, such as BC02 (comprising CpG and aluminum hydroxide), to elicit a robust Th1-type cellular immune response characterized by high levels of interferon-gamma and polyfunctional T cells (NCT05430100). This approach addresses the limitations of the current BCG vaccine, particularly its waning efficacy in adults and its inability to prevent latent TB reactivation. The fusion protein acts as the primary antigenic component in the AEC vaccine, which has progressed to Phase III clinical trials for the prevention of tuberculosis in high-risk populations (NCT05430100).

Other names

AEC vaccine antigenRecombinant Mycobacterium tuberculosis fusion protein ESAT6-CFP10-Mtb32-HspXEC32HESAT6-CFP10-Mtb32-alpha-crystallin fusion

The fusion protein serves as a multi-stage antigen that, when processed by antigen-presenting cells, stimulates the host immune system to produce a Th1-biased response; this includes the activation of antigen-specific CD4+ and CD8+ T cells and the secretion of protective cytokines like IFN-gamma and TNF-alpha, which are essential for controlling Mycobacterium tuberculosis across its active and latent phases (Lu et al., 2015; Wu et al., 2021).