Through the use of antibodies of a human donor with a self -induced hyperimmunity to the snake poison, scientists have developed the most effective antivennene to date, which is protector against the tastes of the snakes of the mamba, the King Cobra and the tiger in the mice tests. Described on May 2 in the Diario de la Press CellThe antivenene combines protective antibodies and an inhibitor of the small molecule and opens a path to a universal anti -narration.
The way we do antivennene has not changed much during the last century. Typically, it implies immunizing horses or sheep with venom of individual snake species and collecting the antibodies produced. While it is effective, this process could lead to adverse reactions to non -human antibodies, and treatments tend to be special and specific in the region.
While exploring ways to improve this process, scientists ran into someone hyperimmune for the effects of snake neurotoxins. “The donor, for a period of almost 18 years, had undertaken hundreds of snacks and autoimmunizations with increasing doses of 16 species of very lethal snakes that would normally kill a horse,” says the first author Jacob Glanville, CEO of Centivax, Inc.
After the donor, Tim Friede, agreed to participate in the study, the researchers found that when exposed to the poison of several snakes for several years, he had generated antibodies that were effective against several snake neurotoxins at the same time.
“The exciting donor was his unique unique immune story in life,” says Glanville. “Not only did he potentially create these widely neutralizing antibodies, in this case, but could lead to a broad spectrum or universal antivenene.”
To build the Antivenom, the team created for the first time a test panel with 19 of category 1 and 2 mortal snakes of the World Health Organization through the ELAPID family, a group that contains approximately half of all venomous species, including coral snakes, mambas, cobras, taipans and kraits. Then, the researchers isolated the target antibodies of the donor’s blood that reacted with neurotoxins found within the species of proven snakes. One by one, the antibodies were tested in poisoned mice of each species included in the panel. In this way, scientists could systematically build a cocktail that includes a minimum but sufficient component number to make all poisons ineffective.
The team formulated a mixture that includes three main components: two donor isolated antibodies and a small molecule. The first donor antibody, called LNX-D09, protected mice of a whole lethal dose of six of the snake species present in the panel. To further strengthen the antisuente, the team added the small molecule VARESPLADIB, a known toxin inhibitor, which granted protection against three additional species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection throughout the panel.
“When we reached the 3 components, we had an amplitude of completely incomparable protection for 13 of the 19 species and then partial protection for the rest we look at,” says Glanville. “We were looking at our list and thought: ‘What is that fourth agent’? And if we could neutralize that, do we get more protection?” Even without a fourth agent, their results suggest that the three -part cocktail could be effective against many other elapides snakes, if not most, not tested in this study.
With the antivenom cocktail, demonstrating to be effective in mice models, the team now seeks to prove its effectiveness in the field, starting by providing the antivenene to dogs taken to veterinary clinics for snake bites in Australia. In addition, they wish to develop an antivenene aimed at the other great snake family, the vipers.
“We are turning the crank now, establishing reagents to go through this iterative process of saying which is the minimal cocktail to provide wide protection against the venom of the viperals,” says Principal Author Peter Kwong, professor of Stock of Medical Sciences at the College of Physics of the University of Columbia of the University of Columbia and surgeons and previously of the National National Health Institutes. “The final product contemplated would be a unique cocktail in the bread panel or potentially would do two: one that is for the Elapides and another that is for the voperids because some areas of the world only have one or the other.”
The other important objective is to address the philanthropic bases, governments and pharmaceutical companies to support the manufacture and clinical development of broad spectrum antivenomo. “This is critical, because although there are millions of snake packaging per year, most of them are in the developing world, disproportionately affecting rural communities,” says Glanville.
This work was supported by the National Institute of Allergies and Infectious Diseases of the National Health Institutes, the small business innovation research program of the National Health Institutes and the United States Department of Energy.