Antibodies as Snakebite Antivenoms: Past and Future

Abstract

Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab')2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.

Keywords: antibodies; antivenom; antivenom design; neglected tropical disease; snake bites; venom.

Figure 1

Geographic distribution of the most medically important snake species in Africa and Latin America.

Figure 2

Different antibody formats with biological activities. IgG: whole molecule. F(ab’)2: product of IgG digestion with pepsin. Fab: product of digestion of IgG with papain. Diabody: non-covalent dimers of scFv fragments. scFv: single-chain variable fragments. VhH: single domain antigen specific fragment. Schematic diagram developed on the biorender platform.