When Nipah or Hendra virus strikes, there is currently nothing doctors can do. These rare but devastating pathogens—cousins in the henipavirus family—kill between 40% and 75% of those they infect, leaving healthcare workers with no vaccines, no therapeutics, and little hope. But new research from the Icahn School of Medicine at Mount Sinai suggests that could change.
Scientists there have developed the first fully human monoclonal antibody cocktail shown to provide complete protection against lethal Nipah and Hendra virus infection, even when given after the infection has already begun. Published in Science Translational Medicine, the breakthrough represents a potential lifeline for communities at risk from these overlooked but terrifying viruses.
The team, led by graduate student Axel Guzman-Solis in the Department of Microbiology, identified two powerful antibodies that attack the virus through completely independent mechanisms. One antibody, called 8G3, targets a critical region of the virus that appears highly resistant to mutation—the virus would need multiple simultaneous genetic changes to escape it, an unlikely event. The other antibody, called 2A1, works in a way that surprised even the researchers: rather than blocking or dislodging a key viral structure, it stabilizes a sugar-containing region on the virus's fusion protein, preventing the virus from entering human cells.
"We were surprised to find that the antibody essentially embraces a structure on the virus that many antibodies try to move out of the way," said Dr. Benhur Lee, Ward-Coleman Chair in Microbiology at Mount Sinai and senior author of the study. "The finding suggests that stabilizing a viral protein can sometimes be just as effective—or even more effective—than disrupting it."
The dual-antibody approach is deliberate. Previous therapeutic candidates focused on blocking one viral protein or the other in isolation, which gave the virus room to evolve resistance. By targeting two different stages of infection at once, the researchers created multiple barriers the virus must overcome—making escape nearly impossible.
One major hurdle the team overcame was the extreme scarcity of human survivor samples needed to develop antibody treatments. To solve this, they used transgenic humanized mice—genetically engineered mice capable of producing fully human antibodies—eliminating the need for the complex additional engineering traditionally required to adapt animal antibodies for human use.
In hamster models exposed to otherwise lethal doses of Nipah virus, the antibody cocktail provided complete protection. While animal results do not guarantee human outcomes, the findings mark an important step toward the first antibody-based therapy for these deadly viruses and offer a promising blueprint for tackling other emerging infectious diseases.
"One of the biggest challenges in developing treatments for henipaviruses is that human survivor samples are extremely rare," Guzman-Solis said. "We wanted to determine whether we could create fully human antibodies that target the virus in multiple ways at once, making it much more difficult for the virus to evolve resistance." With this study, they have answered that question with a decisive yes.