Discovery of Three Human Antibodies Offers Hope for Mpox Treatments

A research team from the Icahn School of Medicine at Mount Sinai has made a significant breakthrough by identifying three potent monoclonal antibodies derived from a patient who recovered from mpox, previously known as monkeypox. These antibodies specifically target the viral protein A35, demonstrating the ability to neutralize the virus effectively in laboratory settings.

In rigorous in vitro tests, these antibodies not only inhibited viral spread but also provided notable protection to rodent models against severe disease, preventing fatalities entirely. The study, which has been published in the journal Cell, further indicates that individuals who have recovered from mpox possess elevated levels of these protective antibodies in their bloodstream, correlating with milder symptoms and a reduced risk of hospitalization.

Mpox is caused by an orthopoxvirus within the same family as the smallpox virus, responsible for over 300 million deaths in the 20th century alone. The disease primarily spreads through close contact with infected individuals, leading to painful rashes, swollen lymph nodes, and fever, with the potential for serious illness and scarring.

A resurgence of mpox cases began globally in 2022, prompting the World Health Organization to declare it a public health emergency on two separate occasions. Currently, there are no approved treatments for mpox, and recent clinical trials of leading therapies have failed to demonstrate efficacy.

Dr. Camila Coelho, an assistant professor of microbiology and senior author of the study, highlighted that their previous research had indicated an unusual increase in antibodies targeting A35 in individuals infected with mpox, compared to those vaccinated for smallpox. This discovery led to the hypothesis that these antibodies would provide robust protection against related orthopoxviruses, addressing an urgent need for effective treatments.

The identified antibodies bind to a particularly conserved region of the A35 protein, which is shared across the orthopoxvirus genus and the wider poxvirus family, making it less susceptible to mutations and immune evasion. Their capacity to prevent viral spread, severe disease, and death positions them as promising candidates for further development into therapeutic options for mpox.

Additionally, the research produced the first detailed crystal structure of a human antibody in complex with an mpox virus protein, providing valuable insights into the virus's vulnerabilities. This study also marks the first occasion monoclonal antibodies against orthopoxviruses have been quantified in human serum, revealing a consistent immune response among those recovering from mpox infection.

While the antibodies represent a significant advancement in potential next-generation therapies for mpox, the research is still in its preliminary stages. Upcoming clinical trials are necessary to assess the antibodies' behavior in the human body, their longevity, distribution post-administration, and overall effectiveness in preventing orthopoxvirus infections.

The research team is moving forward with advanced preclinical safety and efficacy testing of these antibodies while leveraging insights from the study to enhance understanding of the human immune response to mpox.