Universal antivenom to heal all snakebites is closer to reality

In a significant advancement, scientists from Scripps Research have engineered an antibody capable of neutralizing the lethal toxins present in snake venoms from a multitude of species across Africa, Asia, and Australia. Their research marks a pivotal step towards creating a universal antivenom.

The innovative approach utilized laboratory-produced toxins to identify a human antibody, named 95Mat5, which effectively blocks the venom’s harmful effects.

The quest for a universal antivenom

This discovery promises a life-saving solution for treating snakebites globally, especially benefiting regions burdened by snakebite incidents.

Joseph Jardine, PhD, the study’s senior author and an assistant professor of immunology and microbiology at Scripps Research, emphasized the significance of this development.

“This antibody works against one of the major toxins found across numerous snake species that contribute to tens of thousands of deaths every year,” Jardine explained.

“This could be incredibly valuable for people in low- and middle-income countries that have the largest burden of deaths and injuries from snakebites.”

Science of saving lives from snakebites

Snakebite envenoming is a critical issue, particularly in Asia and Africa, causing over 100,000 deaths annually and surpassing the mortality rates of many neglected tropical diseases.

Traditional antivenoms are species-specific and produced through animal immunization, necessitating multiple antivenoms for different regions. The new research offers hope for a universal solution, eliminating the need for numerous antivenoms.

The researchers drew parallels between their antivenom quest and their work on HIV vaccines, focusing on targeting conserved regions of toxins that do not mutate.

By isolating venom proteins from elapids — a major venomous snake group including mambas, cobras, and kraits — they discovered that three-finger toxins (3FTx) have similar sections across species, making them an ideal target for therapeutic intervention.

The team’s innovative screening platform tested over fifty billion human antibodies against the 3FTx protein from the many-banded krait, identifying 3,800 potential candidates.

Journey of antibody 95Mat5

Further testing narrowed this down to 30 antibodies, with 95Mat5 emerging as the most effective across all toxin variants.

“We were able to zoom in on the very small percentage of antibodies that were cross-reactive for all these different toxins,” says Irene Khalek, a Scripps Research scientist and first author of the new paper.

“This was only possible because of the platform we developed to screen our antibody library against multiple toxins in parallel.”

In experiments, 95Mat5 protected mice from the venom-induced death and paralysis caused by several snake species, including the many-banded krait, Indian spitting cobra, black mamba, and king cobra.

The success of 95Mat5 stems from its ability to mimic the human protein usually targeted by 3FTx toxins, a strategy akin to the one used by broad-acting HIV antibodies previously studied by the team.

Jardine expressed enthusiasm about the synthetic creation of 95Mat5, which bypassed the need for animal immunization and snake venom use. However, while 95Mat5 effectively neutralizes elapid venom, it does not counteract viper venom.

“It’s incredible that for two completely different problems, the human immune system has converged on a very similar solution,” says Jardine. “It also was exciting to see that we could make an effective antibody entirely synthetically — we did not immunize any animals nor did we use any snakes.”

Next frontier in universal antivenom research

The team is now exploring antibodies against additional toxins to develop a comprehensive antivenom cocktail, potentially offering universal protection against snakebites.

Khalek envisions this antibody cocktail as a universal antivenom, capable of treating any medically relevant snakebite worldwide.

“We think that a cocktail of these four antibodies could potentially work as a universal antivenom against any medically relevant snake in the world,” says Khalek.

In summary, this life-saving work by Scripps Research scientists in developing an antibody that neutralizes the venom of a wide range of snakes is a monumental stride towards combating the global health crisis of snakebite envenoming.

By leveraging innovative technology to screen billions of human antibodies, they have identified 95Mat5, a potent solution that promises to revolutionize snakebite treatment.

This research gets us one-step closer to a universal antivenom that could save thousands of lives annually, particularly in the most affected regions of Asia and Africa, while also showcasing the power of synthetic biology in addressing complex medical challenges.

The potential to extend this approach to create a comprehensive treatment against all venomous snakes underscores a future where snakebite fatalities become a thing of the past.

The full study was published in the journal Science Translational Medicine.

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