Monkeypox virus antigens A35 and M1 (A35/M1)

Monkeypox virus (MPXV) antigens A35 and M1 are key structural proteins that represent critical targets for the development of vaccines and therapeutic monoclonal antibodies [3, 10]. A35, encoded by the A35R gene, is a glycoprotein primarily associated with the extracellular enveloped virus (EEV) form, where it mediates actin-based motility and efficient cell-to-cell dissemination [1, 2]. M1, encoded by the M1R gene, is a highly conserved myristoylated protein found on the intracellular mature virus (IMV) form and is a vital component of the entry fusion complex (EFC) required for host cell entry [8, 9]. Because MPXV utilizes both IMV and EEV forms for infection and spread, dual targeting of A35 and M1 is essential for achieving robust protective immunity [12, 13]. Experimental mRNA vaccines and monoclonal antibodies targeting these antigens, such as EV35-6, have shown high efficacy in neutralizing the virus and preventing lethal infection in animal models [16, 17]. These proteins are highly conserved among orthopoxviruses, suggesting their potential as targets for broad-spectrum countermeasures against various poxvirus threats [14, 20].

Other names

A35RM1ROPG161OPG162Vaccinia virus A33R homologVaccinia virus L1R homolog

Vaccines targeting A35 and M1 induce neutralizing antibodies and T-cell responses that block the two infectious forms of the virus: the intracellular mature virus (IMV) via M1 and the extracellular enveloped virus (EEV) via A35 [3, 12]. Monoclonal antibodies against A35 prevent viral spread by neutralizing EEV and engaging Fc-mediated effector functions like antibody-dependent cellular cytotoxicity (ADCC) [17, 21].