Antivenom is the only specific medical treatment for venomous bites and stings, serving as a rapid intervention to neutralize toxins in the body. While the treatment is often associated with animals like horses or sheep, the final product is not raw animal blood or serum. The medicine is a highly refined and purified therapeutic agent, resulting from a complex bioprocess that uses the animal’s immune system to create neutralizing antibodies.
Why Animals Are Essential for Antivenom Production
The initial step in manufacturing antivenom relies on the robust immune systems of large mammals, most commonly horses or sheep, but sometimes goats or camels. These animals are selected due to their large size, which allows for a substantial volume of blood plasma to be safely collected, and their vigorous immune responses, which produce large quantities of antibodies.
The process begins with a carefully controlled immunization protocol. The animal is injected with small, non-lethal doses of the target venom over several months. This repeated exposure sensitizes the animal’s immune system, causing its body to recognize the venom’s toxins as foreign invaders.
This biological response involves specialized white blood cells that produce specific proteins called immunoglobulins, or antibodies. These antibodies bind to and neutralize the specific toxins in the injected venom.
Once the animal has reached a hyperimmune state—a high concentration of neutralizing antibodies in its blood—the collection phase begins. A portion of the animal’s blood is safely drawn, and the red blood cells are separated and returned to the donor animal, leaving behind the antibody-rich plasma.
Extracting and Refining the Therapeutic Component
The collected plasma represents the raw material for antivenom production and must undergo extensive processing to become a pharmaceutical product. Refining is necessary because injecting raw animal plasma into a human could cause severe adverse reactions, including life-threatening anaphylaxis or delayed serum sickness. The primary goal of purification is to isolate the therapeutic immunoglobulin G (IgG) and remove all other non-therapeutic animal proteins.
The initial stage involves fractionation, which separates the IgG antibodies from other plasma components. While older methods used chemical agents like ammonium sulfate, modern techniques often use caprylic acid for more efficient separation. Caprylic acid causes most non-antibody proteins to precipitate out of the solution, leaving a purer liquid containing the specific IgG molecules.
Following this initial step, the liquid is subjected to further purification methods, such as chromatography and filtration, to achieve pharmaceutical grade purity. Chromatography passes the solution through a specialized column that separates proteins based on their properties. This ensures that only the highly specific, venom-neutralizing antibodies remain.
The Different Forms of Modern Antivenom
The final stage involves modifying the structure of the purified IgG molecules to improve safety and effectiveness. The full IgG antibody is a large, Y-shaped molecule, and its “stem” portion, the Fc fragment, is responsible for triggering adverse immune reactions in humans. To remove this problematic section, manufacturers use specific enzymes, such as pepsin or papain, to cleave the antibody.
F(ab’)2 Fragments (Pepsin Digestion)
Pepsin digestion cuts the IgG molecule into a smaller fragment called F(ab’)2. This fragment retains both venom-binding arms of the original antibody but lacks the reactive Fc stem. The F(ab’)2 fragment is smaller than the whole IgG molecule, allowing it to move more quickly into tissues to neutralize the venom. Removing the Fc portion significantly lowers the risk of triggering an allergic reaction in the patient compared to older, whole-IgG antivenoms.
Fab Fragments (Papain Digestion)
Alternatively, some processes use papain to cleave the IgG into even smaller Fab fragments, which are half the size of F(ab’)2. The smaller size of the Fab fragment allows for rapid tissue penetration and quick elimination from the body, which can be advantageous in some clinical situations. However, because Fab fragments are cleared from the bloodstream more quickly, they sometimes require repeated dosing to prevent the re-emergence of venom effects, such as recurrent coagulopathy.