Antivenom. As a post script to her article on venom, Bianca op den Brouw looks at how antivenom works, and why is it so difficult to achieve a ‘broad-spectrum’ antivenom? Antivenom is produced by injecting a host animal, such as a horse, with increasing amounts of a given venom (or venoms) over time. The venom toxins are present in quantities small enough that they do not cause too much harm, though they are still detected by the animal’s body as foreign molecules, or antigens. This triggers a response in the immune system of the host animal, inducing the production of antibodies. Antibodies are proteins which are able to recognise an antigenic ‘epitope’: a face, of sorts - a molecular site unique to that antigen. Each type of antibody is essen- tially only able to recognise one face - one epitope - and therefore an antibody is said to be specific to an antigen. This is why multiple vaccines are required for immunisa- tion against the influenza virus – each mutated form of the virus has a different epitope. The ability to recognise epitopes with such high specificity is what enables the immune system to differentiate foreign molecules from normal body molecules. Once an epitope is recognised, the specific antibody will then bind to the antigenic toxin which, depending on the toxin structure, either neutral- ises its harmful activity on the body, or acts as a flag to immune cells to locate and destroy it. As the bioactivity and structure of the numerous toxins composing venom differ, each toxin type has different antigenic properties and a different epitope. Therefore, each toxin type stimulates the production of toxin- specific antibodies by the host animal’s immune system. This cocktail of antibodies is then extracted and purified from the blood of the host animal, and the resulting mixture is used as an antivenom. The composition of the antibodies comprising an antivenom is therefore specific to the venom or venoms used during the antivenom production. This is why different antivenoms are needed for different species of snake. This is also why variation in venom composition within a single snake species can seriously compromise the effectiveness of an antivenom. Image by Chuck Rausin. Further, as the immune response does not discriminate between antigens, antibodies are produced for all components of venom, regardless of how much harm they are capable of inducing. Therefore, if too many different venoms are used to produce an antivenom, the essential antibodies are diluted by the presence of non-essential antibodies, thus requiring substantially more antivenom to achieve the same effect. Left: an Irula tribes- man milks a snake for antivenom production at the Madras Croc Bank. The Irula Co-op will feature in an upcoming article. Image courtesy Madras Croc Bank. Below: variation in venom composition can seriously com- promise the effectiveness of antivenom. Image by Michael Cermak.