Newly created antivenom protects against 19 deadly snakes

By using antibodies from a human donor with a self-induced hyper-immunity to snake venom, US researchers claim to have developed the most broadly effective antivenom to date, which is protective against the likes of the black mamba, king cobra and eastern brown snake in mouse trials. Described in the journal Cell, the antivenom combines protective antibodies and a small molecule inhibitor, and opens a path toward a universal antiserum.

How we make antivenom has not changed much over the past century. Typically, it involves immunising horses or sheep with venom from single snake species and collecting the antibodies produced. While effective, this process could result in adverse reactions to the non-human antibodies, and treatments tend to be species and region-specific.

While exploring ways to improve this process, scientists stumbled upon Tim Friede, who is hyper-immune to the effects of snake neurotoxins. As explained by first author Jacob Glanville, who serves as CEO of Centivax, Friede agreed over a period of 18 years to undertake “hundreds of bites and self-immunisations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse”.

The researchers found that by exposing himself to the venom of various snakes over several years, Friede generated antibodies that were effective against several snake neurotoxins at once. Glanville explained, “What was exciting about the donor was his once-in-a-lifetime unique immune history. Not only did he potentially create these broadly neutralising antibodies; in this case, it could give rise to a broad-spectrum or universal antivenom.”

To build the antivenom, the research team first created a testing panel with 19 of the World Health Organization’s category 1 and 2 deadliest snakes across the elapid family — a group which contains roughly half of all venomous species. Next, researchers isolated target antibodies from Friede’s blood that reacted with neurotoxins found within the snake species tested. 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 formulated a mixture comprising three major 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 present in the panel. To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection across the full panel.

“By the time we reached three 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,” Glanville said. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralise 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.

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. Furthermore, 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,” said lead author Professor Peter Kwong, from Columbia University’s Vagelos College of Physicians and Surgeons and formerly of the US 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,” Glanville said, “because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities.”

Image credit: iStock.com/Ken Griffiths