The impact of a low dose, low volume, multi-site immunization on the production of therapeutic antivenoms in Thailand

Abstract

Therapeutic antivenom against snakes was first produced by Albert Calmette in 1894. Since then antivenoms have saved the life of countless snakebite victims. However, there are still many problems associated with antivenom production, for example variable percentage of responder horses, low neutralizing potency of antivenom, the large amount of snake venom needed for immunization and the difficulties encountered in producing potent polyvalent antivenoms. These problems have led to shortage and high cost of antivenom and, in some cases, failure of treatment. In 1997, a new immunization protocol for antivenom production was reported. It involves the injection of venom at low dose (approx. 2mg/horse) emulsified in Complete Freund's adjuvant in low volume (0.1-0.2ml/site) in a total of 10 sites around the neck area of the horse. This immunization protocol has minimized the local reaction at the injection site thus allowing the use of the potent oil adjuvant. This, together with the increase in total surface area of the droplets, allow a more effective immune response to take place, e.g. enhancing the migration and activation of more antigen presenting cells and lymphocytes. The low dose, low volume multi-site immunization has resulted in dramatic improvements on the antivenom production in terms of amount of venom used for immunization, the time required to reach hyperimmune stage, the percent of responder horses and the potency of the antivenom. Furthermore, this protocol has made it possible to produce potent truly polyvalent antivenoms against several elapid and viperid snakes. This immunization protocol has alleviated various problems associated with antivenom production and has implications for immunization in general. © 2002 Elsevier Science Ltd. All rights reserved.