by If you have been bitten by a venomous snake, the medicine you need is antivenom. Unfortunately, antivenoms are species specific, which means you need to have the right antivenom for the snake that bit you. Most of the time, people have no idea what species of snake bit them. And for some snakes, antivenoms are not available.
New research by myself and my colleagues provides a significant step forward in enabling the development of antigens that will neutralize the effects of venom from any venomous snake: a so-called “universal antivenom”.
In our paper, published in Science Translational Medicine, we describe the discovery and development of a laboratory-made antibody that can neutralize a neurotoxin (a toxin that acts on the nervous system) found in the venom of many snake species around the world.
Venomous snakes kill up to 138,000 people each year, and many more suffer life-changing injuries and mental trauma. Most of the victims are children and farmers.
The active ingredients in antivenoms are anti-toxin antibodies. They are made by injecting horses with small amounts of snake venom and removing the antibodies. This method of making antivenom has been the same for over a century – and it has significant drawbacks.
In addition to being species specific, antigens are also not very potent, so you need a lot of antivenom to neutralize the venom from a bite.
Also, because antivenoms are made in horses, you are very likely to have serious side effects when given, as your body’s immune system will detect and react to the “foreign” horse antibodies. which circulates in your bloodstream.
Antibodies made in the laboratory using genetically modified cells are routinely used in humans to treat cancer and immune disorders. It has long been hoped that the technology used to produce these antibodies can be used to make antivenom and eventually replace traditional antibodies, solving many of the issues currently facing antivenoms.
The antibodies in lab-made antibodies may be “humanized,” a process that tricks your immune system into thinking that foreign antibodies are your own. This may reduce the rate of severe side effects common with horse-derived lubricants.
Paralysis and death are avoided
One of the most important families of toxins in snake venoms are neurotoxins.
These toxins prevent nerve signals from traveling from your brain to your muscles, paralyzing them. This includes paralyzing the muscles that inflate and deflate your lungs, so prey and human victims stop breathing and die.
These neurotoxins are found in the venom of some of the world’s deadliest snakes, including the African black mamba, the Asian cobra and king cobra, and the deadly kraits of the Indian subcontinent.
In our research, we describe the discovery and development of a humanized laboratory-made antibody capable of neutralizing major venom neurotoxins from different snakes from different regions.
The lab-made antibody is called 95Mat5 and was discovered after examining 50 billion unique antibodies to find breakthroughs that can not only recognize the neurotoxin in the venoms of many species but also its deadly effects. to neutralize.
When injected into mice that had received lethal doses of venom, 95Mat5 was able to prevent paralysis and death in all venoms tested.
These results are very encouraging because they show that it is possible to generate laboratory-made antibodies that can broadly neutralize the effects of venom from many species, making the development of universal antibodies a realistic prospect.
However, 95Mat5 is one antibody that only works against neurotoxins. As we said earlier, it takes a handful of antibodies to make a universal antivenom. This is because snake venoms are not just neurotoxins.
Some snake venoms contain haemotoxins, which cause you to bleed, and some contain cytotoxics which destroy the skin and bone. To create a universal antivenom, capable of treating any bite from any snake, we still need to identify additional antibodies that can broadly and potently neutralize the other types of toxins, in the same way as 95Mat5.
We hope that, once identified, these antibodies can be mixed with 95Mat5 to make an antivenom that can neutralize the venom of any snake, regardless of its toxin type.
Because of the need for antibodies for other venom toxins and also the need to ensure any new laboratory-made antivenom is effective and safe in human trials, it will still be several years before antibodies are universal. available to snakebite victims.
Other obstacles must be overcome. It is likely that these new antigens will need to be stored in a refrigerator to avoid loss of effectiveness, so it must be shown that they can be distributed in hot regions of the world that do not have reliable electricity for refrigeration.
Laboratory-made antibodies are some of the most expensive drugs in the world. Although we are hopeful, it remains to be seen whether lab-made repellents will be affordable for the majority of snakebite victims, who are usually some of the poorest people in the world.
This article from The Conversation is republished under a Creative Commons license. Read the original article.
Stuart Ainsworth receives funding from UK Research and Innovation and the National Center for the Replacement, Reduction and Rehabilitation of Animals in Research.
Camille Abada receives funding from the Medical Research Council, UK.
