Effective production of snake antivenom by targeting epidermal dendritic cells via the ‘low dose, low volume, multi-site’ immunization

Abstract

Snakebite envenomation (SBE) is a serious neglected tropical disease that affects about 3 million people every year and causes over 100,000 deaths annually, mostly in developing countries. WHO has pledged to cut in half the morbidity and mortality due to SBE by 2030. Animal plasma-derived antivenoms, produced mostly in horses and sheep, are the main treatment modality. However, for over a century, equine plasma antivenom production has faced many problems. These include: low neutralizing potency, failure of horses to develop a satisfactory immune response, and a long immunization period. These problems have led to antivenom shortages and higher costs resulting in otherwise avoidable morbidity and mortality in snake bite victims. Attempts have been made to improve the antivenom production process. For example, a number of adjuvants designed to improve the immune response have been tested. In 1997, an immunization protocol involving the use of multi-site, low-volume and venom doses was developed and is currently used in antivenom production. This protocol constituted a significant innovation that has resulted in highly potent antivenoms within much shortened immunization periods, with all the immunized horses responding and with much less venom immunogen used. It has resulted in an ample antivenom supply for use in Thailand and neighboring countries and has led to no reported deaths from snakebite in Thailand in the past few years. The effectiveness of this immunization protocol was the result of a strategy based on targeting dendritic cells which play a pivotal role in the immune response process. This communication summarizes the basis and results of this immunization strategy.