Biotechnology
New antivenom shows effectiveness against 17 African snake species
DTU researchers are behind a potentially groundbreaking antivenom that could revolutionize the treatment of venomous snakebites in Africa.
Why is the new antivenom such a major achievement?
Existing antivenoms are produced by immunising horses with snake venom and extracting antibodies from their blood. The result is a large, undefined mixture of antibodies, only a small proportion of which target and neutralize the most dangerous toxins. This method produces a product with great variation in quality and a risk of serious side effects.
“The horses' blood is slightly purified and then given to people who have been bitten by a venomous snake. The antivenom does works, but can cause harmful side effects – it's similar to a blood transfusion from a horse. At the same time, the quality varies because different horses are used in each production,” explains Andreas Hougaard Laustsen-Kiel, continuing:
"Instead, we have developed an antivenom that does not require us to constantly extract antibodies from animals. Instead, we used phage display technology to develop our antivenom. This method makes it possible to select and copy effective antibody fragments (nanobodies) and later produce them on a large scale and with consistent quality. This means that we would be able to produce the antivenom in large quantities without compromising on quality."
There is also no single antivenom that covers all relevant African snake species. This can be particularly problematic if a person is bitten somewhere in Central Africa, where several venomous species live side by side. For example, the venom of the cape cobra and the spitting cobra contain very different toxins: The cape cobra's venom consists primarily of neurotoxins that paralyze the nervous system, while the spitting cobra's venom is rich in cytotoxins, which, among other things, break down tissue and can lead to amputation. This great variation means that an antivenom that works against one species does not necessarily work against another – and therefore it is crucial to develop an antivenom that covers several species.
The researchers have now developed a more effective and broadly effective antivenom by combining eight carefully selected nanobodies into a cocktail that targets venom from 18 medically relevant African snake species. During in vivo testing, the antivenom has shown promising results and covered a wide spectrum of snake species, increasing its potential for effective treatment in real-life cases. In experiments where the antivenom was mixed directly with the venom before being injected, it successfully neutralized venom from 17 out of 18 tested different snake species, with the exception of one of the green mambas. Listed below are the 17 snake species.
| Species | Common Name | Venom Type | Distribution | Wiki |
|---|---|---|---|---|
| Dendroaspis jamesoni | Jameson's mamba | Neurotoxic | Central Africa | https://en.wikipedia.org/wiki/Jameson%27s_mamba |
| Dendroaspis polylepis | Black mamba | Neurotoxic | East-, South-, Central Africa | https://en.wikipedia.org/wiki/Black_mamba |
| Dendroaspis viridis | Western green mamba | Neurotoxic | West-, Central Africa | https://en.wikipedia.org/wiki/Western_green_mamba |
| Hemachatus haemachatus | Rinkhals | Cytotox | South Africa | https://en.wikipedia.org/wiki/Rinkhals |
| Naja anchietae | Cape cobra | Neurotoxic | Southwest-, South Africa | https://en.wikipedia.org/wiki/Anchieta%27s_cobra |
| Naja annulifera | Cape cobra | Neurotoxic | South-, Central Africa | https://en.wikipedia.org/wiki/Snouted_cobra |
| Naja ashei | Spitting cobra | Cytotoxic | East-, Central Africa | https://en.wikipedia.org/wiki/Naja_ashei |
| Naja haje | Egyptian cobra | Neurotoxic | North-, West-, Central Africa | https://en.wikipedia.org/wiki/Egyptian_cobra |
| Naja katiensis | Spitting cobra | Cytotoxic | West-, Central Africa | https://en.wikipedia.org/wiki/Mali_cobra |
| Naja melanoleuca | Forest cobra | Neurotoxic | Central-, West Africa | https://en.wikipedia.org/wiki/Forest_cobra |
| Naja mossambica | Spitting cobra | Cytotoxic | South-, East Africa | https://en.wikipedia.org/wiki/Mozambique_spitting_cobra |
| Naja nigricincta | Spitting cobra | Cytotoxic | West-, Central-, East Africa | https://en.wikipedia.org/wiki/Naja_nigricincta |
| Naja nigricollis | Spitting cobra | Cytotoxic | West-, Central-, East Africa | https://en.wikipedia.org/wiki/Black-necked_spitting_cobra |
| Naja nivea | Cape cobra | Neurotoxic | South Africa | https://en.wikipedia.org/wiki/Cape_cobra |
| Naja nubiae | Spitting cobra | Cytotoxic | Northeast-, East Africa | https://en.wikipedia.org/wiki/Nubian_spitting_cobra |
| Naja pallida | Spitting cobra | Cytotoxic | East-, Central Africa | https://en.wikipedia.org/wiki/Red_spitting_cobra |
| Naja senegalensis | Cape cobra | Neurotoxic | West-, Central Africa | https://en.wikipedia.org/wiki/Senegalese_cobra |
When will the antivenom be available on the market?
Although the antivenom shows promising results, it has not yet been tested on humans, and there is still some way to go before it reaches the market.
The new antivenom doesn't always work as well when it's given after venom exposure. For example, venom from snakes like the black mamba and forest cobra was only partly neutralized. This shows that both what the venom contains and how quickly treatment is given are crucial — and that the antivenom doesn't yet offer complete protection in every situation.
The researchers are still working on fine-tuning and improving the content of the antivenom so that the final version can provide even better protection for snakebite victims and increase the chance of saving lives.
“We have already upgraded one of the nanobodies included and are in the process of improving another. We are constantly learning new things along the way, and it may turn out that some minor adjustments will need to be made in the future,” explains Andreas Hougaard Laustsen-Kiel.
Investments in development and production are difficult to attract in Africa—especially because the countries that are most affected by snakebites often are low-income and have limited purchasing power. Nevertheless, Andreas Hougaard Laustsen-Kiel points out that the new antivenom has economic advantages:
“We estimate that the antivenom can be produced at less than half the current price. This is partly because less active substance is needed to achieve the same effect. At the same time, nanobodies are very physically stable, which means they´re less likely to break down or lose effectiveness during storage. This could lead to fewer losses and lower storage costs."
The researchers are working hard to secure the necessary funding so that development of the antivenom can be accelerated. With the right support, the researchers estimate that clinical trials could begin in one to two years, and that a finished product could potentially be ready within three to four years—with the potential to save thousands of lives.
Andreas Hougaard Laustsen-Kiel has been in dialogue with several companies, organizations, and partners to find a way forward, but no final decisions have been made yet. However, the antivenom appears to be a very promising candidate for a groundbreaking treatment.
“Of course, I have to be careful not to promise too much, but if no other antivenoms emerge that are better, I am quite convinced that our antivenom – compared to those currently on the market – has the broadest coverage of snake species,” says Andreas Hougaard Laustsen-Kiel, continuing:
“We are ready to get started and hope that someone will invest in the project. Our antivenom has the potential to fundamentally change how snakebites are treated around the world.”
Contact
Andreas Hougaard Laustsen-Kiel Professor Department of Biotechnology and Biomedicine Mobile: +45 29881134 ahola@bio.dtu.dk