Mycobacterium tuberculosis antigen fusion protein H56 (H56)

Mycobacterium tuberculosis antigen fusion protein H56 is a recombinant multistage vaccine candidate designed to enhance protection against tuberculosis (TB) across all phases of infection [1, 3]. It is a fusion protein comprising three Mycobacterium tuberculosis antigens: Ag85B and ESAT-6, which are secreted during the early, active stages of infection, and Rv2660c, a protein associated with bacterial latency and persistence [1, 7]. By combining these antigens, H56 aims to provide a broader range of protection than the traditional BCG vaccine, targeting both the initial infection and the dormant bacteria that can lead to later reactivation [3, 12]. In clinical development, H56 is typically formulated with the IC31 adjuvant (a TLR9 agonist) to stimulate a robust Th1-type cell-mediated immune response [3, 8]. This response is characterized by the induction of polyfunctional CD4+ T cells that secrete critical cytokines such as interferon-gamma and tumor necrosis factor-alpha [11, 15, 22]. While H56 has demonstrated safety and immunogenicity in various populations, including BCG-primed individuals and those recently treated for TB, a recent Phase 2b trial failed to show significant efficacy in preventing TB recurrence [18]. This has led to a re-evaluation of its clinical path, although it remains a prominent example of the multistage antigen strategy in TB vaccine research [2, 18].

Other names

Ag85B-ESAT-6-Rv2660c fusion protein [1]Hybrid 56 [6]H56:IC31 [3]H56 antigen [17]

H56 is a multistage vaccine candidate that induces a Th1-polarized cell-mediated immune response by presenting antigens from both the active (Ag85B, ESAT-6) and latent (Rv2660c) phases of Mycobacterium tuberculosis infection to the host immune system [1, 3]. This leads to the activation and expansion of polyfunctional CD4+ and CD8+ T cells that produce protective cytokines such as IFN-gamma, TNF-alpha, and IL-2, which are essential for controlling bacterial replication and preventing disease reactivation [11, 15, 22].