A Universal Cure for Snake Bites

There is a specific venom that has been exposed to the exact venom in question and has made antibodies against it, so it can be collected and given to you to combat the venom making its way through your system. And if you're thinking that horse-based medicine sounds 19th century at best, well %a lot of people% agree with you and are working on ways to remove livestock from the equation. And that's only part of the problem, because you need a different antivenon and a different batch of horses or sheep for pretty much every venom out there. Luckily, researchers are getting closer not just to better antivenoms, but to universal ones. And here is how.

The process of producing antivenoms has remained largely unchanged since its inception in the late 19th century, despite the alarming statistic of approximately 100,000 annual deaths caused by venomous snakebites. Given this grim reality, one might expect that a modernization of the approach is long overdue.

The concept behind antivenoms bears similarities to that of vaccines, with both relying on the body's immune response. When a foreign substance, such as a toxin or virus, infiltrates the body, the immune system generates antibodies to adhere to it. These antibodies then serve as signals to activate other immune cells, prompting them to combat and neutralize the threat.

Scientists discovered that certain animals, like horses, possess sufficiently robust immune systems and size to tolerate controlled exposure to venom. This revelation led to the practice of injecting these animals with small amounts of venom, essentially as a form of immunization. This process was akin to treating them to a somewhat unconventional "snack." As a result, the injected animals would develop antibodies to combat the venom's toxic components.

The human body responds to toxins by producing antibodies to combat them. However, it's crucial to grasp that venom isn't a singular entity; rather, it's a complex mixture of various substances all working together to incapacitate a victim of a snake bite. These toxins are produced by different genes or even gene families within the snake. Consequently, when a horse is exposed to venom, its immune system generates a diverse array of antibodies, each attempting to bind to the various components present in the venom. This results in the production of what's known as polyclonal antibodies, a mixture of antibodies with the capability to attach to multiple venom components simultaneously.

Researchers faced the challenge of isolating these antibodies from the horse's bloodstream, purifying the solution, and converting it into a treatment suitable for human injection. However, a significant limitation is that the antibodies generated by the horse are specific to the type of snake venom it was exposed to, as venom-producing genes vary significantly among snake species. For instance, antibodies derived from rattlesnake venom cannot effectively treat a victim of a black mamba bite.

Furthermore, there's no way to instruct the horse's immune system to produce an equal number of antibodies for each venom component or to prioritize the antibodies against the most dangerous venom elements. Consequently, antivenoms often exhibit an imbalance in their antibody composition. They may lack antibodies capable of targeting some of the most lethal venom components, as these components typically do not trigger a strong immune response.

Complicating matters further, antivenoms can lead to severe allergic reactions in humans because they are derived from animal blood.

Scientists have been diligently working on developing improved antivenoms that can specifically target the most toxic components of venom while being more compatible with the human immune system. However, a significant challenge lies in the fact that it's not practical or safe to expose humans to snake venom and then isolate the antibodies produced as they do with horses. Even if this were possible, it might not yield significantly better results than the traditional horse-based method.

Instead, researchers have adopted a laboratory-based approach, where they isolate the most effective and adhesive antibodies, especially those with an affinity.

Indeed, monoclonal antibodies, which are produced from a single gene, offer the advantage of being highly specific and consistent, making them valuable tools in antivenom development. However, when dealing with venoms, which consist of a multitude of components, the single-target specificity of monoclonal antibodies may seem like a limitation. Venoms are complex mixtures containing various toxins, so having an antivenom that binds to just one component may not be ideal.

To overcome this challenge, researchers have sought to take monoclonal antibodies to the next level by creating broadly-neutralizing monoclonal antibodies. These are antibodies designed to tightly bind to toxins within the same toxin family or those that share similar features. The key tool aiding in the discovery of these powerful antibodies is phage display.

Phage display allows scientists to search through an extensive collection of human antibody genes to identify those that bind most effectively to the toxins found in snake venom. To achieve this, researchers insert these antibody genes into viruses called phages, which typically infect bacteria and have been widely used in laboratories. The phages then produce antibody fragments on their surfaces based on the inserted genetic code. These phages are exposed to the target toxin that researchers want to neutralize, such as a specific venom toxin.

Phages displaying the stickiest antibodies will bind most strongly to the toxins. Researchers can then isolate these phages and identify the antibody gene responsible for the strong binding. This gene can then be used to produce a full-fledged antibody.

However, developing individual monoclonal antibodies for every component in a venom and mixing them together would be extremely labor-intensive, making it less practical than the traditional horse-based method. This is where the clever approach comes in. Researchers can repeat the process with toxins that share similar features, enabling them to find antibodies that bind to multiple toxins, potentially covering a broader spectrum of venom components with fewer antibodies. This approach holds promise for creating more effective and efficient antivenoms.Researchers are making significant strides in the development of antivenoms by focusing on broadly neutralizing antibodies, which can effectively combat entire families of toxins found in venom. For instance, in a 2023 Nature Communications paper, researchers identified a single antibody from a pool of more than 700 candidates. This particular antibody proved highly effective at neutralizing alpha-neurotoxins present in the venom of various deadly snake species worldwide, including king cobras and black mambas. Monoclonal antibodies offer a more precise and consistent approach to antivenom production, representing a significant improvement over traditional methods involving horses.

The potential of broadly neutralizing antibodies lies in their ability to reduce the risk and uncertainty associated with antivenom development. Researchers anticipate that these standardized antivenoms will be the future of snakebite care, offering cost-effective and easily producible treatments. The goal is to make such treatments readily available worldwide, especially in areas inhabited by the most dangerous snake species or remote regions where access to medical care is limited. This approach eliminates the need for livestock in antivenom production.