Every year, between 80,000 and 140,000 people die from snakebites worldwide. Hundreds of thousands more are left with amputated limbs or permanent disabilities.
India accounts for roughly half of these deaths, with around 58,000 people dying from snakebites each year. Many of the victims are farmers, labourers and children in rural communities, bitten while working in the fields or walking home after dark.
Yet the basic way we treat snakebite has changed little in more than a century. Traditional antivenom is made using horses: they are injected with small doses of snake venom, prompting their immune systems to produce antibodies. Blood is then collected from the horse and processed to make the antivenom.
This type of antivenom has saved countless lives, but it has drawbacks. The antivenom can vary from batch to batch, cause severe allergic reactions and is expensive to produce.
It can also offer limited protection. For example, in India, antivenom is mainly made using venoms from four snake species known as the “big four”: the Indian spectacled cobra, common krait, Russell’s viper, and saw-scaled viper. But these antivenoms do not always work well against venoms from other snake species, or populations of the same snake species, found across the country.
We wanted to know whether modern biotechnology could offer a better approach. Our new study in mice, suggests it might.
Small antibodies, big ambitions
Our approach uses nanobodies, tiny versions of antibodies. Antibodies are proteins made by the immune system that recognise and help neutralise harmful substances, including toxins. Nanobodies do a similar job but are much smaller.
Their size could make them useful for treating snakebites because they can move through tissue quickly and reach venom before it causes permanent damage. They can be also be produced in microbes, rather than using horses.
We have already developed nanobodies that can neutralise venoms from African cobras and mambas. Because different cobra species produce many of the same types of toxins, we wanted to see whether these nanobodies could also work against Indian cobra venoms.
In our lab, we mixed five nanobodies and tested them against venoms from several cobra and king cobra species from India. We found that all five were able to target the toxins across the different venoms. This was encouraging because the nanobodies had originally been developed using African snake venoms.
From lab to living animal
We then tested the cocktail in mice. When the venoms and treatment were given together, all of the treated mice survived. While untreated mice died within 30 minutes because of neurotoxicity, typical of cobra bites.
We also tested what would happen if the treatment was given after a simulated bite. The mice received venom first, followed by the nanobody treatment through a vein. This was to simulate someone reaching a clinic after being bitten by a snake.
We found that the treatment still saved the mice when given 20 minutes after the venom. The treatment also prevented the severe effects of the venom, including paralysis and breathing failure.
We checked that the nanobodies did not bind to human proteins, which is important as doing so could cause unwanted side effects. We also found that the nanobodies remained intact at high temperatures, which is important in places where keeping medicines cold can be difficult.
A long road still ahead
These results are promising, but this was a study in mice, so the findings do not necessarily translate directly to people. What works in an animal model may not work in humans in exactly the same way. So the results are best seen as an indication that this approach could be worth developing further.
The cocktail is also not a universal antivenom. Our tests showed that it doesn’t work against Indian kraits, meaning that additional nanobodies would be needed to target these and India’s dangerous vipers. More research is also needed to understand the right dose, how long the treatment lasts and how well it works when treatment is further delayed in larger animal and humans.
The next step would be to test the antivenom in people. First, we would need to make sure it’s safe, decide the right dose and produce it to pharmaceutical standards. The treatment would then be tested in people who come to hospital after being bitten by a snake.
So even though there’s some way to go before this way of making antivenoms could actually be used in humans, these results build on our previous work and suggest that nanobody-based antivenoms could eventually provide a more flexible and effective approach to treating snakebite.
This means that instead of developing a completely new treatment for every snake species, a shared set of nanobodies could potentially be combined and adapted for different geographical regions.
For the people and communities living with the greatest risk of snakebite, this could make an enormous difference. And potentially save tens of thousands of lives every year.
This series was commissioned as part of a partnership between Videnskab.dk and The Conversation, where articles are published in English and Danish.
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