New Delhi: Researchers have developed a recombinant antivenom that has shown broad protection in mice against the venom of spectacled cobras, monocled cobras, and both Indian king cobra species.
A recombinant antivenom is lab-produced. It uses biotechnology and is designed to replace traditional animal-derived antivenoms.
The team from the Indian Institute of Science (IISc) and Germany's Technical University of Denmark said that, unlike conventional antivenoms, recombinant antibodies can be manufactured using microbial and humanised expression systems without repeatedly immunising animals, such as horses.
Conventionally, snake venom is injected into a horse or sheep, which produces antibodies in response. The antibodies are used in making an antivenom -- considered the only solution to treat a snake bite.
"Antivenom treatment has virtually not changed for over 100 years. This is the only next-generation antivenom we have now, which could tackle India's snakebite problem," author Kartik Sunagar, associate professor at the centre for ecological sciences, IISc, said.
Each snake species produces a distinct cocktail of toxins that attack nerves, blood, or tissues, making it difficult to develop a unified treatment, the researchers said.
Current animal-derived antivenoms also have drawbacks such as batch-to-batch variability, side effects, and limited species coverage, they said, adding that their production is costly and outdated, relying on venom milking and animal immunisation, with low yields of active antibodies.
In the study, the team used camelid antibodies, which they developed in a previous study where camelids including alpacas and llamas were immunised with venom from African snake species. Antibodies generated in response were extracted.
The researchers exposed the camelid antibodies to venom from different cobra species in India and found that toxins produced by Indian snakes too could be neutralised.
"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," author Andreas Laustsen, professor at the Technical University of Denmark, said.
The researchers explained that antibodies are usually Y-shaped with both heavy and light-chain proteins. They used a portion at the tip of the Y shape, made up of light-chain proteins that can specifically bind to the venom toxins.
The team 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 the cocktail could neutralise venom activity and prevented the venom from binding to its target receptor.
Testing the antibody cocktail in mice injected with venom, the researchers found that the animals were protected against toxins from spectacled cobras, monocled cobras, and both Indian king cobra species.
Mice were saved 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.
"These findings demonstrate the feasibility of developing broad-spectrum nanobody-based recombinant antivenoms with continent-wide coverage as a safe and regionally adaptable biologic for snakebite envenoming therapy," the authors wrote.