Pioneering Antibodies Against Mpox Offer Promise for New Protective Therapies

A team from the Microbiology Department at the Icahn School of Medicine at Mount Sinai has identified three potent monoclonal antibodies in a person previously infected with mpox (previously known as monkeypox).

These antibodies, targeting the viral protein A35, halted viral spread in lab tests and protected rodents from severe disease while preventing death entirely. The study, published in Cell, shows that people previously exposed to mpox have high levels of these protective antibodies, which correlate with milder symptoms and no need for hospitalization.

Mpox is an orthopoxvirus-caused disease (like smallpox, responsible for over 300 million deaths in the 20th century alone). The virus spreads mainly through close contact, causing painful rashes, swollen lymph nodes, and fever. It can make people severely ill and leave lasting scars.

A global outbreak of mpox began in 2022 and persists today. The World Health Organization has declared it a public health emergency twice, yet no effective treatment exists for this virus family. Recent human clinical trials didn't show efficacy for leading therapies, meaning there's an urgent need for new treatments.

"A prior study in 2023 by our team indicated that human antibodies targeting A35 significantly increased after mpox infection compared to smallpox vaccination or other viral proteins," said Camila Coelho, Ph.D., MBA, Assistant Professor of Microbiology at Icahn and senior author. "We hypothesized these A35-targeting antibodies would protect against orthopoxviruses due to their high genetic similarity."

The newly discovered antibodies target a conserved region across the entire poxvirus family, suggesting they offer robust protection without being prone to mutation or immune evasion. Their ability to block viral spread and prevent severe disease suggests potential as drug candidates for mpox treatment.

"This study represents the first report of the crystal structure of a human antibody bound to an mpox virus protein," said Raianna Fantin, Ph.D., postdoctoral researcher and first author. "This discovery offers critical insights into this pathogen's vulnerabilities."

While promising, clinical trials are necessary to determine these antibodies' longevity, distribution in the body, and efficacy against orthopoxviruses.