Developing snake antivenom sera by genetic immunization: A review

Abstract

Snakebite is a common and generally harmful neglected tropical disease that constitutes a highly relevant public health problem with worldwide mortality estimated to be around 50,000 deaths annually. The only approved and accepted treatment for snakebite envenoming is the use of antivenoms produced by the purification of IgG immunoglobulins from large animals (i.e., horses) immunized against specific snake venoms. Nonetheless, since its conception, by Albert Calmette and Vital Brazil, very little has changed on the way these antivenoms are being produced. Over the last years, on the other hand, with the advance of molecular biology techniques and the rise of transcriptomic and proteomic analysis, the constitution of different snake venoms has been characterized, leading to an increasing demand for the development of new methods of antivenom production, with a more specific immune response and with less adverse effects, such as serum sickness, and even without the need for the collection and maintenance of snake specimens. DNA immunization, an elegant and robust technique of directly injecting a specific antigen DNA coding sequence directly onto the cells of an immunized animal, seems to be a much easier way of developing specific antibodies without the need for recombinant and frequently laborious protein expression and purification from heterologous organisms (i.e., Escherichia coli). In this chapter, we will discuss the advances on the transcriptomic analysis of venom glands from different snake species with a focus on the efforts to develop antivenom sera by DNA immunization and its efficacy in neutralizing the toxic effects elicited by the envenomation from snakebite.