Monoclonal antibodies for Mpox: protective targets and therapeutic potential

To highlight current knowledge on antibody targets in MPXV and evaluate how these insights can inform the development of effective therapeutics or next-generation orthopoxvirus vaccines.

Since 2022, mpox infection has emerged as a global public health concern. While the spread of clade IIb of the monkeypox virus (MPXV) has declined, the new clade Ib is now demonstrating sustained human-to-human transmission outside Central Africa. Despite the rising number of mpox cases, no effective antiviral is currently available for treating mpox or any infection caused by other Orthopoxvirus. Moreover, the only licensed vaccine for mpox prevention was developed based on an attenuated strain of Vaccinia virus and elicits only moderate antibody responses. These challenges demonstrate the urgent need to identify specific viral epitopes among the more than 200 proteins encoded by MPXV that serve as targets for antibody recognition and represent sites of viral vulnerability. Defining such epitopes will be essential for the rational design of next-generation therapeutics and vaccines aimed at achieving durable and broad protection against mpox and other orthopoxvirus infections.

This review summarizes the major antibody targets identified in MPXV, recent advances in understanding antibody-mediated neutralization and protection, and how the therapeutic potential of antibodies can be leveraged to treat mpox and other orthopoxvirus infections as well as to guide the design of effective antiorthopoxvirus vaccines.