BNT166

**BNT166** is an investigational quadrivalent or trivalent mRNA-based vaccine developed by BioNTech for active immunization against mpox (monkeypox), caused by monkeypox virus (MPXV), a member of the Orthopoxvirus family. It encodes conserved surface antigens from both mature virion (MV) and enveloped virion (EV) forms of MPXV, specifically A35 (A35R homolog), B6 (B6R homolog), M1 (M1R homolog), and H3 (H3L homolog) for the quadrivalent version (BNT166a), or without H3 for the trivalent (BNT166c), to elicit neutralizing antibodies, Fc-mediated antibody functions, and T cell responses that block viral replication and infectivity across clades I and IIb. Preclinical studies in mice and cynomolgus macaques demonstrated complete protection against lethal MPXV challenge, including 100% survival, reduced viremia, and suppressed lesions, outperforming or matching modified vaccinia Ankara (MVA) vaccines in disease control. It is currently in a Phase 1/2 dose-escalation trial (NCT05988203) evaluating safety, tolerability, reactogenicity, and immunogenicity in healthy vaccinia-naïve and previously vaccinated adults, with recruitment complete for initial substudies and partnered with CEPI for up to $90M funding to support scalable manufacturing and equitable access.[1][2][3][5][10]