Snaking Toward a Universal Antivenom
Published:18 Apr.2024 Source:Scripps Research Institute
More than 100,000 people a year, mostly in Asia and Africa, die from snakebite envenoming -- rendering it more deadly than most neglected tropical diseases. Current antivenoms are produced by immunizing animals with snake venom, and each generally only works against a single snake species. This means that many different antivenoms must be manufactured to treat snake bites in the different regions. The new research used forms of the toxins produced in the laboratory to screen billions of different human antibodies and identify one that can block the toxins' activity. It represents a large step toward a universal antivenom that would be effective against the venom of all snakes.
Jardine and his colleagues have previously studied how broadly neutralizing antibodies against the human immunodeficiency virus (HIV) can work by targeting areas of the virus that cannot mutate. They realized that the challenge of finding a universal antivenom was similar to their quest for an HIV vaccine; just like quickly evolving HIV proteins show small differences between each other, different snake venoms have enough variations that an antibody binding to one generally doesn't bind to others. But like HIV, snake toxins also have conserved regions that cannot mutate, and an antibody targeting those could possibly work against all variants of that toxin.
But like HIV, snake toxins also have conserved regions that cannot mutate, and an antibody targeting those could possibly work against all variants of that toxin. They found that a type of protein called three-finger toxins (3FTx), present in all elapid snakes, contained small sections that looked similar across different species. Among the 30 antibodies identified in that screen, one stood out as having the strongest interactions across all the toxin variants: an antibody called 95Mat5. While 95Mat5 is effective against the venom of all elapids, it does not block the venom of vipers -- the second group of venomous snakes. Jardine's group is now pursuing broadly neutralizing antibodies against another elapid toxin, as well as two viper toxins.