ANTIVENOMS - A REVIEW OF CURRENT STATUS AND FUTURE-DEVELOPMENTS

Citation
Rdg. Theakston et Dc. Smith, ANTIVENOMS - A REVIEW OF CURRENT STATUS AND FUTURE-DEVELOPMENTS, Biodrugs, 7(5), 1997, pp. 366-375
Citations number
52
Categorie Soggetti
Immunology,"Pharmacology & Pharmacy",Oncology
Journal title
Volume
7
Issue
5
Year of publication
1997
Pages
366 - 375
Database
ISI
SICI code
Abstract
The first advance on crude filtered immune serum or plasma for treatin g systemically envenomed bite victims was the use of IgG (predominantl y equine) precipitated by salt treatment. This was followed by the dev elopment of F(ab')(2) antivenoms, prepared using pepsin digestion to r emove both the highly reactive and nonspecific Fc part of the Ige mole cule and also other non-antibody proteins from the material. Within no rmal limitations, both monospecific (raised against the venom of a sin gle species) and polyspecific (raised against a mixture of venoms of d ifferent species) F(ab')2 antivenoms have proved to be generally effec tive. Many preparations are poor for a wide range of reasons often not related to the method of preparation. The main problem associated wit h them is the high reaction rate in patients caused by complement-medi ated anaphylactic reactions, The most significant recent development i n immunotherapy has been the production of ovine Fab antivenoms prepar ed by replacing pepsin digestion with papain digestion. Theoretically, these possess advantages over F(ab')(2) antivenoms, such as a greater volume of distribution and more rapid kinetics. A major disadvantage of Fab antivenoms is, however, their shorter clearance time, which may result in inadequate blood antivenom concentrations for neutralising venom entering the system late from a venom depot at the bite site. Af finity purification of both Fab and F(ab')(2) antivenoms also results in a major increase in specific activity when compared with the origin al serum source, but this adds greatly to the cost of production, rend ering its use prohibitive in the rural tropics where bites and stings are a major problem. The use of sheep as opposed to horses for immunis ation also results in a cheaper product, due to the lower cost of anim al maintenance; theoretically, sheep preparations should also be safer , causing fewer sensitivity reactions, due to the nature of ovine as o pposed to equine protein. Additionally, it is a great advantage in the rural tropics to have a lyophilised, as opposed to a liquid, antiveno m because of the longer shelf-life of the former at ambient tropical t emperatures. However, lyophilisation does add considerably to the cost of production, involves additional testing and has also in the past b een reported to result in some decrease in neutralising potency. There may well be a case for the development of a combined ovine Fab/F(ab') (2) antivenom which combines the advantages of each product. Alternati ves to conventional antivenoms should also be explored in the future.