Scientists have used antibodies from a human donor with a self-induced hyper-immunity to snake venom to develop what they claim is the most broadly effective antivenom cocktail to date. Their preclinical in vivo tests demonstrate that the antivenom, which comprises two protective antibodies and a small molecule phospholipase inhibitor, varespladib, protected mice from whole-venom challenge of each of all 19 WHO Category 1 and Category 2 snakes, including black mamba, king cobra, and tiger snakes. The team suggests their development opens a path toward a universal antiserum.
First and co-corresponding author Jacob Glanville, PhD, CEO at Centivax, together with researchers at the National Institute of Allergy and Infectious Diseases, and at Columbia University, reported on their studies in Cell, in a paper titled “Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies.” In their paper they concluded, “We demonstrate the successful combination of a minimal cocktail of broadly neutralizing antibodies and a small-molecule inhibitor as a proof of principle for a universal antivenom.”
![Dr Jacob Glanville [Barak Slave Blazer Photography]](https://www.genengnews.com/wp-content/uploads/2025/05/2dDliy5w-201x300.png "Dr Jacob Glanville [Barak Slave Blazer Photography]")
Dr Jacob Glanville [Barak Slave Blazer Photography]
“Snake-bite envenoming, which was added to the World Health Organization (WHO) list of neglected tropical diseases in 2017, causes 81,000–138,000 deaths and 300,000–400,000 permanent disabilities annually,” the authors wrote. How an antivenom is made has not changed much over the past century.
Typically, it involves immunizing horses or sheep with venom from single snake species and collecting the antibodies produced. “For over a century, the standard treatment has been antivenom—a polyclonal serum derived from animals immunized with venom from one or more species of snakes,” the team commented. While effective, this process could result in adverse reactions to the nonhuman antibodies, and treatments tend to be species and region specific. “… most snake species lack a specific antivenom, and efficacy can vary widely even within a species due to geographic genetic variations,” the investigators added.
While exploring ways to improve this process, scientists identified an individual who is hyperimmune to the effects of snake neurotoxins. “The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” Glanville explained.
The individual, Tim Friede, agreed to participate in the study, and consented to a blood sample being taken. “In a non-interventional study design, 40 mL of blood was collected from the donor, after obtaining informed consent,” the researchers noted. “They found that having exposed himself to the venom of various snakes over several years, Friede had generated antibodies that were effective against several snake neurotoxins at once. “What was exciting about the donor was his once-in-a-lifetime unique immune history,” added Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”
![Graphical abstract [Glanville et al. / Cell]](https://www.genengnews.com/wp-content/uploads/2025/05/low-res-300x300.jpeg "Graphical abstract [Glanville et al. / Cell]")
Graphical abstract [Glanville et al. / Cell]
To build their antivenom candidate, the team first created a testing panel with 19 of the World Health Organization’s Category 1 and 2 deadliest snakes across the Elapidae family, a group which contains roughly half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits.
Next, the researchers isolated target antibodies from the donor’s blood that reacted with neurotoxins found within the snake species tested. “Hypothesizing that this repeated exposure to diverse venoms may have selected for broadly reactive antivenom antibodies that recognize conserved epitopes shared across the venom toxins of multiple snake species, we sought to isolate such broadly neutralizing antibodies from the immune memory of this donor,” they stated.
One by one, the antibodies were tested in mice envenomated from each species included in the panel. In this way, scientists could systematically build a cocktail comprising a minimum but sufficient number of components to render all the venoms ineffective.
The team stepwise formulated a mixture comprising three major components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, binds specifically to long-chain neurotoxin (LNX) homologs. Their binding experiments demonstrated that “… LNX-D09 binds specifically to LNX homologs, with breadth extending to all 22 diverse LNX+ elapids tested, and that the antibody binds with high affinity in all genera where affinity was directly evaluated.”
![Authors Mark Bellin and Hannah Hirou, preparing antivenom [Dr Nicholas Bayless]](https://www.genengnews.com/wp-content/uploads/2025/05/sP8AnTXg-300x225.jpeg "Authors Mark Bellin and Hannah Hirou, preparing antivenom [Dr Nicholas Bayless]")
Authors Mark Bellin and Hannah Hirou, preparing antivenom [Dr Nicholas Bayless]
Further tests showed that LNX-D09 protected mice from a lethal dose of whole venom from six of the snake species present in the panel. “LNX-D09 alone fully protected against lethal venom challenges from four cobra species, black mamba, and king cobra, even with a 10-min treatment delay,” the team stated.
To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. “When combined with the PLA2 inhibitor varespladib, complete protection extended to the tiger snake, inland taipan, and coastal taipan, mainly due to the effects of varespladib.”
Finally, they added a second antibody isolated from the donor, called SNX-B03, which was reactive against short-chain neurotoxins, and which extended protection to all 19 members of the diversity panel. “Adding SNX-B03 further extended full protection to the common krait, mulga, Eastern coral snake, and banded krait,” they noted.
![Tim Friede (center), Mark Bellin (right), Joel Andrade (left), Gengan Li (back left), Nicholas Bayless (back center) [Dr Jacob Glanville]](https://www.genengnews.com/wp-content/uploads/2025/05/26LRpo7A-1-225x300.jpeg "Tim Friede (center), Mark Bellin (right), Joel Andrade (left), Gengan Li (back left), Nicholas Bayless (back center) [Dr Jacob Glanville]")
Tim Friede (center), Mark Bellin (right), Joel Andrade (left), Gengan Li (back left), Nicholas Bayless (back center) [Dr Jacob Glanville]
The final antivenom cocktail also provided partial protection against the Russian cobra, Javan spitting cobra, Arabian cobra, Western green mamba, and common death adder.
“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study. “Overall, the cocktail protected against lethal challenges from all 19 elapid species tested, including 10 genera on the WHO’s Category 1 and Category 2 lists, suggesting that LNX, PLA2, and SNX are the dominant toxins in most elapid venoms,” they reported.
![Dr Peter Kwong [NIH]](https://www.genengnews.com/wp-content/uploads/2025/05/QoR5MV92-1-200x300.jpeg "Dr Peter Kwong [NIH]")
Dr Peter Kwong [NIH]
With the antivenom cocktail proving effective in mouse models, the team now looks to test its efficacy out in the field, beginning by providing the antivenom to dogs brought into veterinary clinics for snake bites in Australia. Further, they wish to develop an antivenom targeting the other major snake family, the vipers.
“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” commented author Peter Kwong, PhD, Richard J. Stock professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and formerly of the National Institutes of Health. “The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”
The other major goal is to approach philanthropic foundations, governments, and pharmaceutical companies to support the manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville said.
The post Antivenom Cocktail Protects Against 19 of World’s Deadliest Snakes appeared first on GEN - Genetic Engineering and Biotechnology News.
First and co-corresponding author Jacob Glanville, PhD, CEO at Centivax, together with researchers at the National Institute of Allergy and Infectious Diseases, and at Columbia University, reported on their studies in Cell, in a paper titled “Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies.” In their paper they concluded, “We demonstrate the successful combination of a minimal cocktail of broadly neutralizing antibodies and a small-molecule inhibitor as a proof of principle for a universal antivenom.”
Dr Jacob Glanville [Barak Slave Blazer Photography]
“Snake-bite envenoming, which was added to the World Health Organization (WHO) list of neglected tropical diseases in 2017, causes 81,000–138,000 deaths and 300,000–400,000 permanent disabilities annually,” the authors wrote. How an antivenom is made has not changed much over the past century.
Typically, it involves immunizing horses or sheep with venom from single snake species and collecting the antibodies produced. “For over a century, the standard treatment has been antivenom—a polyclonal serum derived from animals immunized with venom from one or more species of snakes,” the team commented. While effective, this process could result in adverse reactions to the nonhuman antibodies, and treatments tend to be species and region specific. “… most snake species lack a specific antivenom, and efficacy can vary widely even within a species due to geographic genetic variations,” the investigators added.
While exploring ways to improve this process, scientists identified an individual who is hyperimmune to the effects of snake neurotoxins. “The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” Glanville explained.
The individual, Tim Friede, agreed to participate in the study, and consented to a blood sample being taken. “In a non-interventional study design, 40 mL of blood was collected from the donor, after obtaining informed consent,” the researchers noted. “They found that having exposed himself to the venom of various snakes over several years, Friede had generated antibodies that were effective against several snake neurotoxins at once. “What was exciting about the donor was his once-in-a-lifetime unique immune history,” added Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”
Graphical abstract [Glanville et al. / Cell]
To build their antivenom candidate, the team first created a testing panel with 19 of the World Health Organization’s Category 1 and 2 deadliest snakes across the Elapidae family, a group which contains roughly half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits.
Next, the researchers isolated target antibodies from the donor’s blood that reacted with neurotoxins found within the snake species tested. “Hypothesizing that this repeated exposure to diverse venoms may have selected for broadly reactive antivenom antibodies that recognize conserved epitopes shared across the venom toxins of multiple snake species, we sought to isolate such broadly neutralizing antibodies from the immune memory of this donor,” they stated.
One by one, the antibodies were tested in mice envenomated from each species included in the panel. In this way, scientists could systematically build a cocktail comprising a minimum but sufficient number of components to render all the venoms ineffective.
The team stepwise formulated a mixture comprising three major components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, binds specifically to long-chain neurotoxin (LNX) homologs. Their binding experiments demonstrated that “… LNX-D09 binds specifically to LNX homologs, with breadth extending to all 22 diverse LNX+ elapids tested, and that the antibody binds with high affinity in all genera where affinity was directly evaluated.”
Authors Mark Bellin and Hannah Hirou, preparing antivenom [Dr Nicholas Bayless]
Further tests showed that LNX-D09 protected mice from a lethal dose of whole venom from six of the snake species present in the panel. “LNX-D09 alone fully protected against lethal venom challenges from four cobra species, black mamba, and king cobra, even with a 10-min treatment delay,” the team stated.
To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. “When combined with the PLA2 inhibitor varespladib, complete protection extended to the tiger snake, inland taipan, and coastal taipan, mainly due to the effects of varespladib.”
Finally, they added a second antibody isolated from the donor, called SNX-B03, which was reactive against short-chain neurotoxins, and which extended protection to all 19 members of the diversity panel. “Adding SNX-B03 further extended full protection to the common krait, mulga, Eastern coral snake, and banded krait,” they noted.
Tim Friede (center), Mark Bellin (right), Joel Andrade (left), Gengan Li (back left), Nicholas Bayless (back center) [Dr Jacob Glanville]
The final antivenom cocktail also provided partial protection against the Russian cobra, Javan spitting cobra, Arabian cobra, Western green mamba, and common death adder.
“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study. “Overall, the cocktail protected against lethal challenges from all 19 elapid species tested, including 10 genera on the WHO’s Category 1 and Category 2 lists, suggesting that LNX, PLA2, and SNX are the dominant toxins in most elapid venoms,” they reported.
Dr Peter Kwong [NIH]
With the antivenom cocktail proving effective in mouse models, the team now looks to test its efficacy out in the field, beginning by providing the antivenom to dogs brought into veterinary clinics for snake bites in Australia. Further, they wish to develop an antivenom targeting the other major snake family, the vipers.
“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” commented author Peter Kwong, PhD, Richard J. Stock professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and formerly of the National Institutes of Health. “The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”
The other major goal is to approach philanthropic foundations, governments, and pharmaceutical companies to support the manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville said.
The post Antivenom Cocktail Protects Against 19 of World’s Deadliest Snakes appeared first on GEN - Genetic Engineering and Biotechnology News.