Antidote Developed Against Venom of World's 19 Deadliest Snakes

For 18 years, a volunteer has subjected himself to hundreds of bites and self-immunizations with increasing doses from 16 highly lethal snake species that would normally kill a horse, until the most effective antivenom to date was developed, protecting against species like the black mamba, king cobra, and tiger snake in mouse trials.

Scientists led by Columbia University in the United States have developed this antidote, which combines protective antibodies and a small molecule inhibitor, paving the way for a universal antiserum, as described in the journal 'Cell' by Cell Press.

The production of antivenoms has not changed much in the last century. It typically involves immunizing horses or sheep with venom from a single snake species and collecting the produced antibodies. While effective, this process could cause adverse reactions to non-human antibodies, and treatments are often specific to each species and region.

While exploring ways to improve this process, scientists encountered someone hyperimmune to the effects of snake neurotoxins. The donor, Tim Friede, has allowed himself to be inoculated with venom from various snakes for nearly 18 years, generating effective antibodies against several snake neurotoxins simultaneously. "The exciting aspect of the donor was his unique immune history," exclaims Jacob Glanville, CEO of the American company Centivax, Inc. "Not only did he potentially create these broadly neutralizing antibodies, but in this case, it could lead to a broad-spectrum or universal antivenom."

To develop the antivenom, the team first created a test panel with 19 of the World Health Organization's (WHO) category 1 and 2 deadliest snakes from the elapid family, a group that includes approximately half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits. Next, researchers isolated target antibodies from the donor's blood that reacted with the neurotoxins present in the analyzed snake species. One by one, the antibodies were tested on mice envenomed by each species in the panel. This way, scientists were able to systematically create a combination with a minimal but sufficient number of components to neutralize all the venoms.

The team formulated a mixture with three main components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, protected mice from a lethal dose of whole venom from six of the snake species in the panel. To further enhance the antiserum, the team added the small molecule varespladib, a known toxin inhibitor, which provided protection against three more species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection to the entire panel.

"By reaching the three components, we achieved unprecedented total protection for 13 of the 19 species and subsequently partial protection for the remaining ones we analyzed," says Glanville. Following the efficacy of the antivenom cocktail in murine models, the team now seeks to test its effectiveness in the field, starting by administering the antivenom to dogs brought to veterinary clinics for snake bites in Australia. Additionally, they aim to develop an antivenom targeting the other major snake family: vipers.

"We are working diligently to prepare reagents that allow this iterative process: determining what is the minimal sufficient combination to provide broad protection against viperid venom," details the lead author, Peter Kwong, professor of Medical Sciences at Columbia University's Vagelos College of Physicians and Surgeons and former member of the National Institutes of Health. "The final product envisioned would be a unique combination of antivenom or, potentially, two: one for elapids and another for vipers, as in some parts of the world only one combination exists."