For a snakebite victim, every minute matters. But the treatment available today still largely depends on an antivenom system developed more than a century ago — one that has limitations in the range of snake species it can cover and the amount of antibodies required.
Now, researchers at the Indian Institute of Science (IISc) and the Technical University of Denmark (DTU) have taken a step towards changing that.
The teams have developed a recombinant, nanobody-based antivenom that showed broad protection against venom from several geographically distinct cobra and king cobra species found in India. The study, published in Science Translational Medicine, could offer a blueprint for developing next-generation antivenoms tailored to the snakes responsible for bites in different regions.
Snakebite remains a major public health problem in India, which reports nearly 50,000 deaths annually, the highest number of snakebite deaths globally.
Snake venom is not a single poison. It is a complex mixture of toxins, and its composition varies between species and even across geographical regions. Some toxins attack the nervous system, while others damage blood, muscles, or tissues.
The conventional antivenom used in India is produced by immunising horses with snake venom and then extracting antibodies from their blood. While the treatment can be lifesaving, its effectiveness can vary depending on which snake caused the bite.
There can also be batch-to-batch variation, adverse reactions, and the need to administer relatively large quantities of antivenom.
“The antivenom treatment has virtually not changed for over 100 years,” said Kartik Sunagar, Associate Professor at IISc’s Centre for Ecological Sciences. “This is the only next-generation antivenom we have now, which could tackle India’s snakebite problem.”
The researchers used tiny antibody fragments known as nanobodies. Unlike conventional antibodies, these fragments are small and can be engineered and produced in the laboratory.
The IISc and DTU teams selected five nanobodies that could recognise and bind to important toxins found in the venom of several Indian cobra species. Together, the five formed an antibody cocktail designed to block the toxins from interacting with their target receptors.
The approach builds on earlier work by the DTU team, which used camelids such as alpacas and llamas to generate antibodies against snake venom. The useful antibody fragments were subsequently isolated and produced using microbial cells.
For the current study, the researchers tested these antibodies against venom from Indian cobra species.
The results were encouraging. In experiments involving mice, the antibody cocktail protected against venom from spectacled cobras, monocled cobras and both Indian king cobra species. Importantly, the treatment was effective even when administered 30 minutes after venom injection.
According to Sunagar, some mice that had developed paralysis and other characteristic neurotoxic symptoms recovered and became asymptomatic after treatment.
One of the potential advantages of recombinant antivenom is that it does not depend on repeatedly immunising horses and extracting antibodies from their blood.
Instead, selected antibodies can potentially be manufactured more consistently using laboratory-based systems. The technology could also allow additional antibody components to be incorporated to cover toxins from other medically important snakes.
That raises the possibility of developing antivenoms specifically suited to different regions, where the species and venom profiles responsible for serious bites may differ.
“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,” said Andreas Laustsen, Professor at DTU.
The researchers also believe that the high potency of carefully selected antibodies could eventually help reduce the quantity of antibody needed for treatment, potentially addressing some of the cost and safety concerns associated with administering large doses.
However, the findings are still at the preclinical stage. Protection demonstrated in mice does not mean that the treatment is ready for use in people. Further studies will be needed to establish its safety, effectiveness, appropriate dosing, manufacturing feasibility and performance in humans.
For India, where snakebite disproportionately affects rural and vulnerable communities, the larger significance lies in the possibility of moving from a largely one-size-fits-all approach towards precision antivenom designed around the snakes and toxins that cause disease in specific regions.
The study also highlights why tackling snakebite requires expertise spanning toxinology, antibody engineering and protein science.
As co-author Anne Ljungars of DTU put it, solving a global health problem such as snakebite requires interdisciplinary collaboration.
The challenge now is to translate this promising laboratory advance into an affordable, scalable treatment that can eventually reach the people who need it most, said the study.
