Mpox Death in Mice Prevented by Antibodies Targeting A35 Protein
August 27, 2025
The recent discovery of human monoclonal antibodies targeting the mpox viral protein A35 marks a major step forward in the search for effective treatments against orthopoxviruses. Researchers at Mount Sinai found that these antibodies not only blocked viral spread in the lab but also protected rodents from severe disease and death. Importantly, A35 is highly conserved across the poxvirus family, reducing the likelihood of mutations that escape immune defenses. This breakthrough opens the door to promising therapeutic candidates that could be tested in humans and underscores the critical role of antibody research in combating the ongoing mpox resurgence.
A study published in Cell has uncovered three monoclonal antibodies from a person previously infected with mpox that target the viral protein A35, offering strong potential for new therapeutic strategies against orthopoxviruses. The research, led by the Icahn School of Medicine at Mount Sinai, showed that these antibodies fully blocked viral spread in vitro, prevented severe disease in rodents, and completely protected them from death.
Mpox, a disease caused by monkeypox virus (MPXV), continues to pose a global threat with sustained human-to-human transmission and evolving epidemiology. Effective therapies for orthopoxviruses have historically been scarce, leaving clinicians reliant on limited antivirals like tecovirimat, which has not consistently demonstrated efficacy in trials. This new discovery could change the treatment landscape by providing a more targeted option rooted in the human immune response.
The A35 protein emerged as an especially promising target because it is highly conserved not only across orthopoxviruses but also across the broader poxvirus family. This means that antibodies targeting A35 are less likely to be undermined by viral mutations or immune escape. Researchers also report that individuals recovering from mpox consistently generate antibodies targeting this epitope, reinforcing its role as a key vulnerability in the virus. Importantly, this is the first reported crystal structure of a human antibody bound to an mpox protein, providing detailed insights into viral weaknesses that can guide drug and vaccine development.
The Mount Sinai team plans to move these antibodies into advanced preclinical testing while using structural findings to inform strategies for enhancing immune responses through vaccination. If successful, this work could yield the first antibody-based therapy against mpox and potentially other poxviruses, offering a powerful new tool for outbreak response and global biodefense.