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AERAS-456 (H56:IC31) is a recombinant subunit vaccine candidate developed for the prevention and adjunctive treatment of tuberculosis (TB). It was created through a collaboration between the Statens Serum Institut (SSI) and Aeras, utilizing the IC31 adjuvant technology from Valneva. The vaccine is composed of the H56 fusion protein—which integrates three *Mycobacterium tuberculosis* antigens: Ag85B, ESAT-6, and Rv2660c—formulated with the IC31 adjuvant. Ag85B and ESAT-6 are early-stage antigens associated with active bacterial replication, while Rv2660c is a latency-associated antigen, enabling the vaccine to target the pathogen across its entire lifecycle. The IC31 adjuvant consists of a cationic antimicrobial peptide (KLK) and a synthetic oligodeoxynucleotide (dIdC), the latter of which acts as a TLR9 agonist to promote a robust Th1-polarized immune response. AERAS-456 has been evaluated in Phase I and Phase II clinical trials for its safety and immunogenicity in healthy individuals, patients with latent TB, and those who have recently completed treatment for active pulmonary TB.
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