IISc and DTU Scientists Engineer Nanobody Antivenom Against Indian Cobra Venoms

Researchers at the Indian Institute of Science (IISc), Bengaluru, working with the Technical University of Denmark (DTU), have developed a recombinant antivenom built from engineered antibody fragments that offers broad protection against the venoms of several cobra and king cobra species found in India.

The treatment is a cocktail of five nanobodies — small antibody fragments — that bind to and neutralise venom toxins. In experiments on mice, the cocktail not only prevented death but also reversed paralysis and other neurotoxic symptoms when administered up to 30 minutes after envenomation.

India records nearly 50,000 snakebite deaths each year, the highest of any country. Snakebite is classified as a neglected tropical disease, and each snake species produces a distinct mix of toxins that attack nerves, blood or tissues, complicating the search for a single treatment.

Conventional antivenoms, derived from animals, carry drawbacks including variability between batches, side effects and limited species coverage, besides being costly and outdated to produce.

To address this, Kartik Sunagar, Associate Professor at IISc's Centre for Ecological Sciences, collaborated with Andreas Laustsen, Professor at DTU, to engineer antibodies effective against venoms from various Indian cobra species. The findings were published in the journal Science Translational Medicine.

The team exposed camelid antibodies to venom from different Indian cobra species and found that the antibodies could also neutralise related toxins produced by Indian snakes. In earlier work, Laustsen and colleagues immunised camelids such as alpacas and llamas with venoms from various African snake species, extracted the resulting antibodies and used microbial cells to mass-produce them in the laboratory.

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

Antibodies are typically Y-shaped, with both heavy- and light-chain proteins. The researchers used a portion at the tip of the Y, made up of light-chain proteins that can specifically bind venom toxins. Sunagar and his colleagues isolated a cocktail of five such fragments capable of binding toxins across the cobra species tested. The cocktail neutralised venom activity and prevented the venom from binding to its target receptor.

When tested in mice injected with venom, the antibody cocktail protected the animals against toxins from spectacled cobras, monocled cobras and both Indian king cobra species. It also saved mice from death even 30 minutes after venom injection.

"Even mice that were paralysed or had typical neurotoxic symptoms would revert to a completely asymptomatic state," Sunagar said.

The project brought together expertise in toxinology, antibody engineering and protein science across several countries, addressing a global health problem.