Antivenom is a biological medicine consisting of antibodies developed to bind to the toxic components of venom. It is produced by licensed manufacturers under the supervision of health authorities and is used only in healthcare facilities, at a physician's discretion. What to do when a scorpion sting is suspected is clear: stay calm and call 112. Whether antivenom is needed is assessed at the healthcare facility.
This article is not about the clinical use of antivenom but about the material at the start of its production chain. It explains why this role, touched on briefly in the article on uses of venom in research, demands so much care.
What kind of product is antivenom?
The general principle is that a mammal's immune system recognizes venom as a foreign substance and produces antibodies against it. These antibodies are purified from plasma obtained from the animal's blood. During purification, the antibody molecule is often split into fragments, and the part that carries the binding function is retained. The resulting product is called monovalent if it is prepared against the venom of a single species and polyvalent if it is prepared against the venoms of several species.
The concept emerged at the end of the 19th century, when it was shown that immunity induced in animals could be transferred by serum. The first snake antivenoms were developed in this period, and products against scorpion venoms followed the same principle in later years. The basic idea has not changed in more than a century; what has changed are purification techniques and quality control methods.
The main links in the chain can be summarized roughly as follows:
| Link | General content | Role of venom |
|---|---|---|
| Venom supply | Collection of material with documented species identity and origin | Starting material |
| Characterization | Definition of the composition by analytical methods | Measured material |
| Antibody production | The animal's immune response and collection of plasma | Input that stimulates immunity |
| Purification | Separation of the antibodies from the rest of the plasma | Not directly involved |
| Quality control | Measurement of the product's capacity to bind and neutralize venom | Benchmark |
The table shows that venom plays two separate roles in the chain: at the start, the input that stimulates the immune response; at the end, the benchmark against which the product is tested.
Why is species identity decisive?
Antibodies recognize only the structures they have encountered. An antivenom is therefore only as broad in scope as the toxin diversity represented by the venom used in its production. The venoms of different species carry different peptide families; compositional differences have been reported even between different geographic populations of the same species. The concentration of most medically significant scorpion species in a single family, as described in the article on the Buthidae, focuses this work on particular genera.
Venom from a misidentified species may lack the expected toxins or contain unexpected ones. For this reason, alongside the species name, the starting material's records also include how identification was carried out, the origin of the individuals and the period in which the material was collected. Pooling material from a large number of individuals helps to balance out differences between individuals and obtain a more representative mixture.
Taxonomic updates complicate the picture further. When a new species is described, the question may arise again as to which population venom studies previously published under another species name actually belonged to. This is why, when comparing old and new records, it becomes important to know the collection site as well as the species name.
The challenge of small toxins
A large share of the components held responsible for serious effects in scorpion venom are small peptides. Structures of low molecular weight are not recognized by the immune system as readily as large proteins. The result can be a strong antibody response against large but relatively harmless proteins in the venom and a weaker one against small but potent peptides. This mismatch is one of the most intensively studied issues in the field of scorpion antivenom and makes detailed knowledge of the venom's peptide content all the more important.
Venom as reference material
In the quality control of an antivenom batch, the key question is to what extent the product can neutralize a given amount of venom. The answer is obtained by comparison with a reference venom that has the same characteristics every time. If the reference material varies, it is impossible to tell whether a difference between two measurements comes from a change in the product or in the reference.
Potency measurements have traditionally relied on animal experiments. To reduce animal use, methods that measure the binding of antibodies to venom components in the laboratory are being developed. Approaches that use chromatography and mass spectrometry to examine which venom components an antivenom captures have also become widespread in this field. Whichever method is used, a well-characterized venom is the common starting point.
Another requirement for reference material is that it lasts over time. A quality control programme must be able to work with the same reference for years; the reference venom is therefore divided into many small containers, and each container is used only once. When the reference runs out, the new batch that replaces it is brought into use after comparison with the old one, so that the measurement series is not broken.
The qualities generally sought in a venom intended as a reference are:
- Documented species identification and a known geographic origin
- A batch record traceable from collection to shipment
- A form that can be stored for a long time, usually lyophilized
- Analytical characterization covering protein content, chromatographic profile and electrophoresis bands
- Records of storage conditions and of each opening
On the research side, in addition to animal-derived antibodies, work is also under way on recombinant antibodies produced in the laboratory and on small antibody fragments. These approaches, too, begin with the identification of the target toxins; whether traditional or new, every method has a well-defined venom at the start of the chain.
Where our product fits
Our product is crude venom obtained from the species Androctonus turkiyensis; it is not an antivenom and is not administered to humans or animals. It is supplied to institutions for research and industrial use only. In the independent laboratory analysis of the reference batch, 37 proteins or peptides were separated by RP-HPLC, a band profile was obtained by SDS-PAGE and the α-KTx 3.6 peptide was identified. These values may vary from batch to batch; the full results are available on the analysis page.
