Healthcare (Commonwealth Union) – Snakes have always been one of the most feared creatures on earth. With the exception of pythons and rat snakes that do not use venom on their prey, it is the venom that is of most concern to our fear of snakes.
In a key scientific development, scientists from the Centre for Ecological Sciences (CES) at the Indian Institute of Science (IISc), together with scientists from the Technical University of Denmark (DTU), have developed a recombinant antivenom based on nanobodies. The treatment has demonstrated broad effectiveness against venoms from several geographically distinct cobra and king cobra species found in India. The findings were published in Science Translational Medicine.
Because each snake species produces a unique combination of toxins that can damage the nervous system, blood or body tissues, creating a single antivenom that works across species has proved challenging. Conventional antivenoms derived from animals also face limitations, including variation between production batches, adverse reactions and restricted effectiveness against different snake species. Their manufacture is expensive and relies on traditional processes involving venom extraction and animal immunisation, which typically produce relatively small quantities of effective antibodies.
Seeking a more effective approach, Kartik Sunagar, Associate Professor at CES, joined forces with Andreas Laustsen, Professor at DTU, to design antibodies capable of neutralising venom from multiple cobra species found across India.
Unlike traditional antivenoms, these recombinant antibodies can be produced through microbial and humanised expression systems, eliminating the need to repeatedly immunise horses or other animals. Researchers can also incorporate additional antibody components to broaden protection against other medically significant snake species. This could eventually allow recombinant antivenoms to be specifically designed for particular regions and the snake species found there.
Sunagar pointed out that antivenom treatment has remained largely unchanged for more than a century.
He further indicated that this represents the first next-generation antivenom they have that could potentially address India’s enormous snakebite burden.
In an earlier study, Laustsen and his colleagues collected blood from camelids, including alpacas and llamas, that had been immunised with venom from several African snake species. They isolated antibodies generated in response to the venom and used microbial cells to produce large quantities of these antibodies in the laboratory. The antibodies were subsequently displayed on bacteriophages and tested against venoms from different snake species. This enabled the researchers to identify antibody fragments capable of binding to and neutralising venom toxins.
For the latest study, the teams led by Sunagar and Laustsen used the same collection of camelid-derived antibodies and tested them against venoms from several cobra species found in India. The researchers discovered that the antibodies were also capable of neutralising related toxins produced by Indian cobras.
Laustsen indicated that this study provides a framework for developing recombinant antivenoms suited to different parts of the world by focusing on the toxin families responsible for disease in locally prevalent snake species.
Antibodies typically have a Y-shaped structure composed of heavy- and light-chain proteins. The researchers focused on a section at the end of this structure, formed from light-chain proteins, which is capable of selectively recognising and attaching to venom toxins. Sunagar and his team identified a combination of five antibody fragments, known as nanobodies, that could target toxins produced by the different cobra species included in their study. The nanobody cocktail was able to neutralise the venom’s effects and block the toxins from attaching to their target receptors.
The researchers subsequently tested the cocktail in mice that had been injected with snake venom. The treatment protected the animals from toxins produced by spectacled cobras, monocled cobras and both species of Indian king cobra. Remarkably, the treatment was still capable of preventing death when in mice administered up to 30 minutes after the venom had been injected.
“Even mice that were paralysed or had typical neurotoxic symptoms would revert to a completely asymptomatic state,” added Sunagar.
