A new antivenom works against the venoms of 17 out of 18 African elapid snake species, including cobras, mambas and rinkhals, in animal studies – pointing towards a future in which knowing exactly which type of snake delivered the bite may no longer be essential. This could prove crucial in regions where thousands of people die each year because the correct antivenom is not available. But a researcher warns that the road from the laboratory to patients may be long.
Every year, thousands of people in Africa die from snakebites – often because the necessary treatment is either unavailable or does not match the specific type of snake that caused the bite.
Today, treating snakebite envenoming still depends on having an antivenom that matches the venom involved. In animal studies, the new antivenom works against venoms from 17 of 18 cobra, mamba and rinkhals species and can therefore be used across multiple elapid species. This points towards a new type of broad-spectrum antivenom – not developed for a single type of snake but as a platform capable of covering many species.
“It is a major breakthrough that we have not only developed an antivenom that works against several types of snake venom but also shown that it reduces tissue damage around the bite site. Our antivenom holds great potential to save thousands of lives in Africa each year,” says Andreas Hougaard Laustsen-Kiel, Professor at the Department of Biotechnology and Biomedicine at the Technical University of Denmark in Kongens Lyngby.
The research has been published in Nature.
Why snake antivenom is so difficult to develop
Developing effective antivenom against snake venom is difficult.
Snake venoms do not comprise a single toxin that needs to be neutralised but dozens to hundreds of different toxins that vary across snake species – including neurotoxins that paralyse the nervous system and cytotoxins that destroy tissue.
In addition, venom composition varies between snake species – and even within the same species, it can differ with geography and age.
Today, antivenom is produced by injecting venom into a horse, which then produces antibodies against it. These antibodies are purified from the horse’s blood and used as treatment.
More effective, broad-spectrum antivenoms are needed so that treatment does not depend on correctly identifying the snake.
If the description is wrong, a patient may receive antivenom that does not work against the species responsible for the bite.
“A somewhat similar approach was used, for example, in producing insulin; in the past, insulin had to be extracted from animals and injected into humans. Today, insulin is produced in a completely different way – using biotechnological fermentation – and we would like to apply this approach to producing snake antivenom,” explains Andreas Hougaard Laustsen-Kiel.
Towards a broader antivenom
In the study, venoms from 18 different elapid snake species, including cobras, mambas and rinkhals, were used to immunise llamas and alpacas.
Llamas and alpacas are particularly useful for antivenom development because they produce special heavy-chain-only antibodies, from which nanobodies can be derived. These are much smaller and more stable than conventional antibodies.
The selected snakes are of interest because they comprise around three quarters of the most venomous snakes in Africa. The other major group is the vipers, which have a different type of venom containing other toxins and therefore require separate antivenoms, which the researchers are now also working to develop.
Once the llamas and alpacas had developed antibodies to the snake venoms, the researchers set out to identify nanobodies with promising properties in terms of toxin neutralisation, stability and ease of production.
Andreas Hougaard Laustsen-Kiel compares the process to fishing: the researchers put a snake toxin on the hook and “catch” the nanobodies that bind to it.
From these, they can select nanobodies that bind to several different toxins within a toxin family. The result was eight nanobodies that each bind to and neutralise multiple toxins within a toxin family – a key property for developing broad-spectrum antivenoms.
Neutralises venom from 17 of 18 snake species
After identifying the eight nanobodies, the researchers combined them into a single antivenom – a principle that could form the basis for future modular, broad-spectrum antivenoms.
First, venoms from each of the 18 snake species were individually mixed with the nanobody cocktail and injected into mice.
Under normal circumstances, the mice would have died from the venom. But they did not. The nanobodies neutralised the venom from 17 of the 18 snake species.
The researchers then simulated a snakebite by first injecting venom into the mice and subsequently administering the antivenom.
This mimics a real-life scenario in which a person is bitten by a snake and receives treatment shortly afterwards. This experiment also showed that the antivenom worked as intended.
Finally, the researchers found that the antivenom not only saved the mice’s lives but also reduced tissue damage around the injection site.
“In this respect, too, our antivenom performs better than existing antivenoms. You can never completely prevent tissue damage, but with our antivenom we were able to limit it more effectively than existing treatments,” says Andreas Hougaard Laustsen-Kiel.
A costly treatment for overstretched health systems
Even with these promising results, there are many challenges in getting the antivenom to those who could benefit from it.
First, extensive work is still needed to test the antivenom in larger animals and in humans, after which the relevant health authorities must approve it.
An even greater challenge may be that producing antivenom is not free. It costs money – and money is in short supply in many African healthcare systems.
For this reason, building a viable business around producing an antivenom that could save lives in some of the world’s poorest countries is difficult. As a result, attracting the necessary investment to develop it can be challenging.
“The problem is that it is not a medicine you take every day for the rest of your life but a treatment you receive once after being bitten. For it to be commercially viable, each treatment would have to be expensive – and those bitten by snakes are often among the poorest people in the poorest regions of the world’s poorest countries,” says Andreas Hougaard Laustsen-Kiel.
He is therefore working with colleagues to find models that can get the antivenom to those who need it.
“We need to find a different way of doing this. In addition, we do not need to worry about whether the antivenom will still work in 50 or 100 years, because snake venom does not evolve in the same way as bacteria or viruses. This means that a product like this could remain on the market far into the future,” says Andreas Hougaard Laustsen-Kiel.
