Antivenom is a biological product derived from the plasma of animals, not raw blood. This plasma contains specific antibodies that counteract venom toxins, making antivenom the only effective treatment for venomous bites or stings. Animals like horses and sheep are routinely used because their robust immune systems produce a high concentration of antibodies after controlled exposure to the venom.
The Role of Animals in Antibody Production
The process begins with hyperimmunization, where small, non-lethal doses of venom are injected into a large animal over several months. This controlled exposure stimulates the animal’s immune system to recognize the venom’s components as foreign threats. The animal then produces specific antibodies, primarily immunoglobulin G (IgG), which are designed to bind to and neutralize the venom toxins.
Scientists prefer large animals like horses and sheep because their size allows for the safe collection of a large volume of antibody-rich plasma, maximizing yield. Sheep are known for their fast immune response, often producing high titers of specific antibodies that remain elevated. Once the antibody concentration reaches a sufficient level, blood is drawn, and the plasma component is separated for manufacturing.
Transforming Plasma into Antivenom
The plasma harvested contains antibodies but also other proteins that would cause adverse reactions if injected directly into a human. Purification begins by separating the plasma from red blood cells, followed by fractionation to isolate the IgG antibodies. Techniques like caprylic acid precipitation are used to separate the desired IgG from other plasma proteins, increasing the purity of the therapeutic material.
A key manufacturing step involves enzymatic digestion of the IgG molecule, typically using pepsin. This enzyme cleaves the antibody into smaller, therapeutic F(ab’)2 fragments. This fragmentation removes the Fc portion, which is responsible for triggering historical allergic reactions in patients. The resulting fragments retain their ability to bind to the venom while significantly improving the product’s safety profile.
Safety and Advancements in Antivenom Technology
The historical use of less purified animal serum often led to serum sickness, a delayed allergic response caused by the human immune system reacting to foreign proteins. Modern purification and fragmentation techniques, yielding F(ab’)2 fragments, greatly reduce the amount of foreign protein injected, mitigating this risk. The purified fragments are also formulated to be more stable and easier for the body to process.
Researchers are exploring new methods to move beyond animal-derived products, such as using recombinant DNA technology to create monoclonal antibodies in a laboratory setting. While this technology holds promise for safer antivenom, the vast majority of life-saving antivenoms still rely on the established process of harvesting and purifying antibodies from hyperimmunized animals like sheep and horses.