Hendra and Nipah viruses (henipaviruses, HNVs) are emerging threats to public health. These viruses primarily reside in bats, but they can lead to viral spillovers into humans and cause often fatal respiratory and neurological disease—from 40 to 75 percent. Presently, there are no treatments for humans, with only one human monoclonal antibody (mAb) therapy in clinical trials.
However, progress is limited to animal mAbs, which may provoke adverse immune responses in humans. Consequently, there is a great need for human-compatible antibodies. Yet, there is a scarcity of patient samples from which to isolate human antibodies against henipaviruses. To address this limitation, researchers at Icahn School of Medicine at Mount Sinai used a humanized mouse model to produce therapeutic mAbs. In their study, published in Science Translational Medicine, the team isolated two mAbs with the ability to neutralize Nipah and Hendra viruses by binding to the viral fusion protein or the receptor binding protein, respectively.1 When combined in a cocktail, these mAbs protected Nipah virus-infected hamsters. These findings underscore a promising antiviral strategy.
HNV relies on two of its surface glycoproteins to enter the host cell: the receptor binding protein (RBP) and the fusion protein (F). To infect cells, the RBP binds to the host cell. This action then signals the F protein to trigger a conformational change, fusing the viral and host cell membranes.
So, the researchers wanted to generate antibodies capable of targeting RBP and F. To do this, they immunized humanized mice with HNV pseudoviruses, which are lab-engineered viral particles that mimic the envelope protein structure of HNVs but are stripped of their lethal genetic material. This immunization prompted the rodents to produce human antibodies. Then, the team isolated 10 neutralizing antibodies against multiple strains of both HNVs.
From these, the researchers isolated two antibodies named 8G3 and 2A1 from the rodents. Through functional cell assays, they found that 8G3 neutralized HNVs by competing with RBP. They also found that 2A1 targeted a prefusion epitope involved in F activation, preventing the typical conformational change and neutralizing the viruses.
Next, the researchers investigated the antibodies’ effectiveness in an animal model. Because monotherapy with anti-F and anti-RBP can result in escape mutations, a genetic change in a pathogen that alters its surface proteins to evade treatment, the researchers tested a cocktail of 8G3 and 2A1 in animals. They gave hamsters a lethal dose of Nipah virus and split the animals into early (day one and three) and late (day two and four) treatment groups. Hamsters received doses of h8G3 or h2A1 and then received the cocktail postinfection.
Early treatment with h8G3, h2A1, or the cocktail resulted in 100 percent survival compared to animals that did not receive the antibodies. Animals that received late treatment developed clinical signs of disease and lost weight; however, late treatment still improved the animals’ survival compared to control hamsters.
Overall, these findings demonstrate that immunization of humanized mice can elicit the production of human mAbs against HNVs. Although these mAbs could neutralize HNVs alone, their combinatory effects were additive and protected hamsters from lethal doses of virus. While the researchers acknowledge further development is needed, this antibody cocktail represents a promising antiviral strategy in combating HNV outbreaks.
- Guzmán-Solís AA, et al. A cocktail of human mAbs targeting the henipavirus fusion and receptor binding proteins provides cross-species neutralization. Sci Transl Med. 2026.
