Scientists Develop First Broad Antivenom to Counter Snakebites

Thanks to a man who allowed himself to be bitten by his pet snakes, scientists have developed the first broad-spectrum antivenom that neutralizes the neurotoxins in 19 of the world’s deadliest snakes.

Peter Kwong, the Richard J. Stock Professor of Medical Sciences at Columbia University Vagelos College of Physicians and Surgeons, co-led the research, which was reported in the journal Cell.

Two antibodies found in the man’s blood provided the basis for the antivenom cocktail that provides complete protection against most of the 19 species in the elapid family of snakes considered of greatest medical concern by the World Health Organization.

The need for better antivenoms for snake bites is vital. Snake venom kills more than 100,000 people each year and causes more than 400,000 permanent disabilities.

Existing antivenoms have several shortcomings. Since current antivenoms typically work for a single species or a few related snakes, the victim or health care worker must correctly identify the snake that bit. Most antivenoms contain antibodies from animals that have the potential to cause serious side effects. And with more than 600 venomous snake species on Earth, most lack a specific antivenom.

The ideal antivenom would be made with small molecules and/or human antibodies capable of neutralizing any snake toxin.

As a structural biologist focused on infectious diseases, Kwong was unaware of the need for better antivenoms until he met Jacob Glanville, an immunologist and entrepreneur and the study’s co-leader, at a Gates Foundation meeting.

“One of the main implications of my HIV vaccine work is the discovery that a single human antibody can recognize a broad variety of molecules,” says Kwong, who directs the Aaron Diamond AIDS Research Center at Columbia University. At a 2019 vaccine meeting, Glanville asked Kwong to join his search for antibodies that can recognize a wide variety of snake toxins, not just one. “He needed a structural biologist to characterize the interaction between identified antibodies and toxins,” Kwong says, “and my group and I took on this collaborative role.”

Glanville hypothesized that repeated exposure to venoms from dozens of different snakes may have created very powerful and broadly reactive antibodies in a snake enthusiast who had documented more than 200 bites and 600 self-injections of venom from a wide variety of poisonous snakes over nearly two decades.

The researchers combed through billions of different antibodies in the man’s blood and found two that were particularly protective against neurotoxins commonly found in snakes in the elapid family, which includes coral snakes, mambas, cobras, taipans, and kraits.

A cocktail containing the two antibodies and a third drug—varespladib, a known toxin inhibitor—provided full antivenom protection against 13 species and partial protection against six species.

So far, the researchers have only tested their antivenom cocktail in lab mice. To get a more realistic idea of their cocktail’s efficacy, the researchers plan to collaborate with veterinarians in Australia, where elapids are the sole family of venomous snakes and frequently bite dogs and other pets.

Kwong’s structural analyses revealed how the antibodies bind to and neutralize the neurotoxins, information that is helping the researchers find additional antibodies in the man’s blood that neutralize neurotoxins from other snake families.

“We are testing additional broadly acting antibodies, and since there are only about a dozen toxin classes, a cocktail that neutralizes all of them is likely to be truly universal,” Kwong says.