Engineered antibodies offer broad protection against deadly cobra toxins

by Indian Institute of Science

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A research team has developed a recombinant, nanobody-based antivenom that offers broad protection against venom from geographically diverse cobra and king cobra species in India. The study is published in Science Translational Medicine and includes researchers at the Centre for Ecological Sciences (CES), Indian Institute of Science (IISc), and collaborators at the Technical University of Denmark (DTU).

Snakebite is a neglected tropical disease, causing hundreds of thousands of deaths and disabilities each year. India alone reports nearly 50,000 deaths annually, the most snakebite deaths in the world.

Each snake species produces a distinct cocktail of toxins that attack nerves, blood or tissues, making it difficult to develop a unified treatment. Current animal-derived antivenoms also have drawbacks, such as batch-to-batch variability, side effects and limited species coverage. Their production is costly and outdated, relying on venom milking and animal immunization, with low yields of active antibodies.

To solve this problem, Kartik Sunagar, associate professor at CES, collaborated with Andreas Laustsen, professor at DTU, to engineer antibodies that would work against venom produced by various cobra species in India.

Unlike conventional antivenoms, these recombinant antibodies can be manufactured using microbial and humanized expression systems without repeatedly immunizing animals such as horses. Additional antibody components can be added to expand protection to other medically important snakes, allowing future recombinant antivenoms to be tailored for different regions or species.

Building on camelid antibodies

"Antivenom treatment has virtually not changed for over 100 years," Sunagar says. "This is the only next-generation antivenom we have now, which could tackle India's snakebite problem."

In a previous study, Laustsen and colleagues used the blood of camelids (like alpacas and llamas) immunized with venom from various African snake species, extracted antibodies produced against the venom and used microbial cells to mass-produce these antibodies in the lab. They then displayed the antibodies on bacteriophages, exposed them to venom from various snake species and isolated specific antibody fragments that could bind to and neutralize the toxins in the venom.

In the current study, Sunagar and Laustsen's teams used the same set of camelid antibodies but exposed them to venom from different cobra species in India. They found that the antibodies could neutralize related toxins produced by Indian snakes as well.

"This work provides a blueprint for how recombinant antivenoms can be tailored to different regions of the world by targeting the toxin families that drive disease in local snake species," Laustsen says.

Protection at low doses

Antibodies are usually Y-shaped, with both heavy- and light-chain proteins. The researchers used a portion at the tip of the Y shape, which is made up of heavy-chain proteins that can specifically bind to venom toxins. Sunagar and colleagues isolated a cocktail of five such antibody fragments, called nanobodies, that could bind to toxins in the various cobra species they tested. They found that this cocktail could neutralize venom activity and prevent the venom from binding to its target receptor.

The team then tested the antibody cocktail in mice injected with venom and found that it protected the animals against toxins from spectacled cobras, monocled cobras and both Indian king cobra species. It was also able to save mice from death even 30 minutes after venom injection. "Even mice that were paralyzed or had typical neurotoxic symptoms would revert to a completely asymptomatic state," Sunagar says.

Previously, researchers have often required relatively large amounts of monoclonal antibodies to neutralize snake venom in mice, raising concerns about the doses that might ultimately be needed in humans, Sunagar explains. "Here, we showed that it is possible to neutralize venom using very small amounts of carefully selected and engineered antibodies. This could potentially help address some of the cost and safety concerns associated with administering large quantities of antibodies," he adds.

"This project combined expertise in toxinology, antibody engineering and protein science across several countries," says co-author Anne Ljungars, a senior researcher at DTU. "Solving a global health problem like snakebite requires exactly this kind of interdisciplinary collaboration."

Publication details

Arpan Samanta et al, Oligoclonal nanobody-based recombinant antivenom protects mice challenged with venom from cobras and king cobras from India, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.aed4290

Journal information: Science Translational Medicine

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