H4:IC31 tuberculosis vaccine (H4:IC31)

H4:IC31 is an investigational subunit vaccine candidate developed for the prevention of tuberculosis (TB) [1, 12]. It consists of a recombinant fusion protein, H4 (also known as HyVac4), which combines two immunodominant Mycobacterium tuberculosis antigens, Ag85B and TB10.4, with the synthetic cationic adjuvant IC31 [3, 8]. The IC31 adjuvant is composed of a leucine-rich peptide (KLK) and a Toll-like receptor 9 (TLR9) ligand (ODN1a), which together form a particulate delivery system that enhances the magnitude and duration of the cellular immune response [2, 7]. The vaccine is primarily designed as a booster for individuals previously vaccinated with Bacille Calmette-Guérin (BCG) to induce long-lasting, polyfunctional CD4+ T-cell responses characterized by the production of IFN-gamma, TNF-alpha, and IL-2 [8, 9]. Clinical trials have demonstrated that H4:IC31 has an acceptable safety profile, with common side effects including injection site pain and fatigue [1, 9]. While it has shown promise in preventing sustained M. tuberculosis infection in phase 2 trials, it did not meet the primary efficacy endpoint for preventing initial infection in some populations [1, 12].

Other names

AERAS-404SSI/SP H4-IC31HyVac4/IC31Ag85B-TB10.4:IC31H4:IC31 vaccine particle

H4:IC31 induces a Th1-polarized immune response by delivering mycobacterial antigens (Ag85B and TB10.4) alongside the IC31 adjuvant, which triggers TLR9 signaling to activate dendritic cells and promote the expansion of polyfunctional CD4+ T cells.