Snake Bites

Scientists discovered antibodies that protect against a host of lethal snake venoms. Scripps Research scientists have developed an antibody that can block the effects of lethal toxins in the venoms of a wide variety of snakes found throughout Africa, Asia and Australia. The antibody, which protected mice from the normally deadly venom of snakes including black mambas and king cobras, is described on February 21, 2024, in Science Translational Medicine. The new research used forms of the toxins produced in the laboratory to screen billions of different human antibodies and identify one that can block the toxins' activity. It represents a large step toward a universal antivenom that would be effective against the venom of all snakes. "This antibody works against one of the major toxins found across numerous snake species that contribute to tens of thousands of deaths every year," says senior author Joseph Jardine, PhD, assistant professor of immunology and microbiology at Scripps Research. "This could be incredibly valuable for people in low- and middle-income countries that have the largest burden of deaths and injuries from snakebites." More than 100,000 people a year, mostly in Asia and Africa, die from snakebite envenoming -- rendering it more deadly than most neglected tropical diseases. Current antivenoms are produced by immunizing animals with snake venom, and each generally only works against a single snake species. This means that many different antivenoms must be manufactured to treat snake bites in the different regions. Jardine and his colleagues have previously studied how broadly neutralizing antibodies against the human immunodeficiency virus (HIV) can work by targeting areas of the virus that cannot mutate. They realized that the challenge of finding a universal antivenom was similar to their quest for an HIV vaccine; just like quickly evolving HIV proteins show small differences between each other, different snake venoms have enough variations that an antibody binding to one generally doesn't bind to others. But like HIV, snake toxins also have conserved regions that cannot mutate, and an antibody targeting those could possibly work against all variants of that toxin. In the new work, the researchers isolated and compared venom proteins from a variety of elapids -- a major group of venomous snakes including mambas, cobras and kraits. They found that a type of protein called three-finger toxins (3FTx), present in all elapid snakes, contained small sections that looked similar across different species. In addition, 3FTx proteins are considered highly toxic and are responsible for whole-body paralysis, making them an ideal therapeutic target. With the goal of discovering an antibody to block 3FTx, the researchers created an innovative platform that put the genes for 16 different 3FTx into mammalian cells, which then produced the toxins in the lab. The team then turned to a library of more than fifty billion different human antibodies and tested which ones bound to the 3FTx protein from the many-banded krait (also known as the Chinese krait or Taiwanese krait), which had the most similarities with other 3FTx proteins. That narrowed their search down to about 3,800 antibodies. Then, they tested those antibodies to see which also recognized four other 3FTx variants. Among the 30 antibodies identified in that screen, one stood out as having the strongest interactions across all the toxin variants: an antibody called 95Mat5. "We were able to zoom in on the very small percentage of antibodies that were cross-reactive for all these different toxins," says Irene Khalek, a Scripps Research scientist and first author of the new paper. 'This was only possible because of the platform we developed to screen our antibody library against multiple toxins in parallel." Jardine, Khalek and their colleagues tested the effect of 95Mat5 on mice injected with toxins from the many-banded krait, Indian spitting cobra, black mamba and king cobra. In all cases, mice who simultaneously received an injection of 95Mat5 were not only protected from death, but also paralysis. When the researchers studied exactly how 95Mat5 was so effective at blocking the 3FTx variants, they discovered that the antibody mimicked the structure of the human protein that 3FTx usually binds to. Interestingly, the broad-acting HIV antibodies that Jardine has previously studied also work by mimicking a human protein. "It's incredible that for two completely different problems, the human immune system has converged on a very similar solution," says Jardine. "It also was exciting to see that we could make an effective antibody entirely synthetically -- we did not immunize any animals nor did we use any snakes." While 95Mat5 is effective against the venom of all elapids, it does not block the venom of vipers -- the second group of venomous snakes. Jardine's group is now pursuing broadly neutralizing antibodies against another elapid toxin, as well as two viper toxins. They suspect that combining 95Mat5 with these other antibodies could provide broad coverage against many -- or all -- snake venoms. "We think that a cocktail of these four antibodies could potentially work as a universal antivenom against any medically relevant snake in the world," says Khalek. This work was supported by funding from the National Institutes of Health (R35 CA231991, U01 AI142756, RM1 HG009490, R35 GM118062, R35 GM118069), the Damon Runyon Cancer Research Foundation (2406-20), the Jane Coffin Childs Fund, the Mark Foundation for Cancer Research and the Howard Hughes Medical Institute.

COPENHAGEN, Denmark, Jan. 30, 2024 /PRNewswire/ -- VenomAid Diagnostics (Abbr.: VenomAid), the Danish company developing snakebite diagnostics, announced today that it has successfully extended its seed round to $1.8 million with continued support from a select group of private Business Angels and the philanthropic venture fund Good Ventures LLC. The announcement comes on the annual World NTD day, which serves as a catalyst to translate awareness into action and secure increased resources for neglected tropical diseases (NTDs). Founded in 2018 with a mission of reducing the global burden of snakebite, VenomAid has developed an affordable, easy-to-use, in vitro diagnostic test for management of snakebite. The simple, portable device uses a small amount of blood from the patient to quickly identify the type of venom in the patient's bloodstream. This enables healthcare workers to quickly and accurately diagnose the type of snakebite and administer the appropriate treatment, increasing the chances of survival and reducing the risk of permanent disability. Snakebite envenoming is a neglected tropical disease that kills >100,000 people and maims >400,000 people every year. According to the World Health Organisation, there are approximately 5.4 million snakebites each year, with up to 2.7 million resulting in severe envenoming. One of the main challenges in treating snakebites is the difficulty in identifying the type of snake that bit the victim. This is important because different types of snakes have different venom, and the appropriate treatment varies depending on the type of venom. Despite this global health burden, there are currently no widely available rapid diagnostic tests for snakebite envenoming. VenomAid aims to fill this critical need by providing affordable and rapid diagnostic tests that empowers more clinical personnel to correctly diagnose snakebites. VenomAid's lead asset, the Bothrops kit, has shown ability to detect snake venoms from the Bothrops genus in clinically relevant concentrations, despite the challenge of venom variations. The test can be used even in resource-limited settings, enabling a larger fraction of the healthcare system to offer management of snakebites and thereby stock the life-saving treatment. Currently, snakes from the Bothrops genus account for 70-80% of snakebites in South America, resulting in death and disabilities among those inflicted, leading to even larger socio-economic consequences. ‍Jonas Arnold Jürgensen, CEO of VenomAid said: "We are thrilled to announce the continued support from our group of investors on World NTD Day. This funding will allow us to execute our vision of bringing affordable diagnostics to snakebite victims around the world. More specifically, we are now gearing up for clinical pilots in Brazil and plan to initiate manufacturing of our rapid tests, bringing us closer to market. We believe that VenomAid's technology has the potential to transform snakebite management by reducing time from bite to treatment, and thus save lives, prevent disabilities, and drive economic growth in some of the world's poorest and most marginalised communities." For more information and/or media enquires please contact: VenomAid Diagnostics ApS ‍Jonas Arnold Jürgensen, CEO & Co-founder +45 3048 2747 [email protected] About VenomAid Diagnostics ( ) VenomAid Diagnostics is a Nordic medtech startup innovating toxin-diagnostics, mainly within animal envenomations. VenomAid has recently established state-of-the-art facilities in Denmark and built know-how within Lateral Flow Assay development targeting toxins. VenomAid's current flagship project is the Bothrops kit – a diagnostic device for the Brazilian and Latin American market that can detect envenomings from Lancehead snakes and thereby guide selection of antivenom. About Good Ventures LLC ( ) Good Ventures LLC invests in for-profits related to human health and well-being, and donates its net earnings to the Good Ventures Foundation. The following files are available for download: SOURCE VenomAid Diagnostics A/S

Scientists have called for simple, effective steps to cut the number of people bitten by venomous snakes. Scientists have called for simple, effective steps to cut the number of people bitten by venomous snakes. About 140,000 people die each year from snakebites worldwide, and another 400,000 are left with permanent disability. The World Health Organisation now recognises snakebites as a "neglected tropical disease," and has committed to halving snakebite deaths and disabilities by 2030. A new study -- by an international team led by the University of Exeter -- surveyed people in Tamil Nadu, a snakebite hotspot in India. The findings show that most people (69%) take steps to prevent snakebites, but the measures taken don't always reflect evidence-based advice. Promoting locally practical methods -- with the support and understanding of local people -- could save many lives. "We need to get serious about this problem," said Harrison Carter, who led the study as part of a masters in Conservation and Biodiversity at the University of Exeter. "Much of the focus has been on antivenom treatment, but this isn't always practical due to issues such as cost, frozen storage and distance from treatment centres. "Amazingly, despite the increased international focus on this issue, hardly any research has examined what people do to prevent snakebites and how we can improve that. "With collaborative action from bodies including governments, donor agencies, researchers and communities, we can drastically reduce the number of lives ended or severely impacted by snakebites." The risk of snakebites also leads to an unknown number of snakes being killed. As well as the impact on snake conservation, this could affect the important role of snakes in providing "ecosystem services" (benefits to humans) such as pest control. By eating rodents, snakes remove crop pests and reduce disease risk for humans. The researchers surveyed 535 people in rural agricultural communities in Tamil Nadu, asking what anti-snakebite measures they take, and what stops them doing more to protect themselves. Tamil Nadu contains just 5% of India's population, but an estimated 20% of the country's snakebite deaths happen there. Of the people who took steps to prevent snakebites, more than half (59%) exclusively used measures supported by evidence and government guidelines. These include keeping homes and surroundings clean and tidy, and using torches at night. However, 41% relied fully or partially on measures not recognised by research or official advice -- such as sprinkling salt, garlic, turmeric or bleach as deterrents. "In every community we visited, people knew someone who had died or been seriously injured recently by a snakebite," said Carter, now at the University of Oxford. "The really important point is to find solutions that work in a certain location, and that people find practical and easy to use. "For example, some farmers in Tamil Nadu have previously been given boots for protection -- but many work in paddy fields, where boots immediately get stuck in the wet ground. "The most obvious -- and yet easily overlooked -- option is to talk to people and ask them what they need. "Of the people in our survey who took no protective measures, almost half said that, on reflection, they felt they should. "By working with local partners who have the trust of their communities, simple measures can be promoted to make a real difference." Tamil Nadu has high numbers of four venomous snakes whose bites can seriously affect humans: the spectacled cobra, the Russell's viper, the saw-scaled viper and the common krait. These snakes are widespread in tropical regions -- and the researchers say their approach to bite prevention could also be applied across the topics. The research team included the universities of São Paulo and Witwatersrand, NOVA University Lisbon and the Madras Crocodile Bank Trust.