Polyvalent Snake Antivenoms: Production Strategy and Their Therapeutic Benefits

Abstract

Snake envenomation remains an important yet neglected medical problem in many countries, with around five million people affected, and over a hundred thousand deaths annually. Plasma-derived antivenoms are the main therapeutic agent available. Monovalent antivenoms are produced via the immunization of large animals, e.g., horses, with one venom, after which the horse serum can neutralize the homologous venom, with minimal or no cross neutralization against other venoms. It is necessary, therefore, for the culprit snake to be identified, so that the appropriate specific antivenom can be selected. Polyvalent antivenoms (pAVs) are produced via immunization with a number of snake venoms, and the serum can neutralize all the venoms used in its production. Thus, pAVs can be used to treat several venoms from a country/region, and the identification of the culprit snake is not necessary. There are various parameters and processes involved in the production of pAVs, depending on the requirements and resources available. Most commercial pAVs use a mixture of both elapid and viperid venoms as immunogens, while some pAVs use either elapid or viperid venoms. Some pAVs are produced through the mixing of more than one monovalent or polyvalent antivenom. These various types of pAVs have their own characteristics, and have benefits and drawbacks. The major benefits of pAVs are the wide coverage of many medically important venoms, including many heterologous venoms. They also remove the need to identify the culprit snake, and they can be produced at a lower cost than several monovalent antivenoms. Interesting polyvalent antivenoms, termed 'syndromic pAVs' (s-pAVs), have recently gained attention. They are produced for use according to the syndromes manifested in snakebite patients. The venoms that produce these syndromes are used as immunogens in the production of 'syndromic antivenoms'. For example, 'neurotoxic polyvalent antivenom' and 'hematotoxic polyvalent antivenom' are produced using the neurotoxic elapid and hematotoxic viperid venoms as immunogens, respectively. They were first marketed by the Thai Red Cross in 2012, and have since gained attention as a possible therapeutic modality to help solve the problem of snakebite envenomation globally. The merits of these s-pAVs, including their efficacy and wide paraspecificities, are discussed.

Keywords: antivenom; equine; hematotoxins; neurotoxins; polyspecific; snake; syndromic polyvalent.

Figure 1

The horse antibody response to immunization with viperid (Bitis arietans arietans, Echis ocellatus) and elapid (Dendroaspis polylepis, Naja nigricollis) venoms, using different immunological adjuvants. The antibody response is expressed as mg venom neutralized per ml of antiserum. This Figure was published in Arguedas et al. ‘Comparison of adjuvant emulsions for their safety and ability to enhance the antibody response in horses immunized with African snake venoms’. Vaccine X 2022, 12, 100233 [23].

Figure 2

(A) Patients with coagulopathy and bleeding (signs of hematologic disorder) caused by a Daboia russelli bite. (B) A patient showing bilateral ptosis (signs of neurotoxic poisoning caused by an elapid (Bungarus caeruleus) bite. Photographs courtesy of Professor David A Warrell.

Figure 3

The two syndromic polyvalent antivenoms: “Neuro Polyvalent Antivenin” (right) and “Hemato Polyvalent Antivenin” (left), produced by Queen Saovabha Memorial Institute, The Thai Red Cross Society.