Bothropic antivenom based on monoclonal antibodies, is it possible?

• Published in: Toxicon (Oxford) 2013-09, Vol.71, p.49-56
• Main Authors: Frauches, Thiago S., Petretski, Jorge H., Arnholdt, Andrea C.V., Lasunskaia, Elena B., de Carvalho, Eulógio C.Q., Kipnis, Thereza L., da Silva, Wilmar D., Kanashiro, Milton M.
• Format: Article
• Language: English
• Subjects: ammonium sulfate; Ammonium Sulfate - metabolism; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antivenins - immunology; Antivenins - pharmacology; Antivenom; antivenoms; Blood Coagulation - drug effects; Bothrops; Bothrops atrox; Caprylates - metabolism; Crotalid Venoms - antagonists & inhibitors; Crotalid Venoms - immunology; Crotalid Venoms - toxicity; Electrophoresis, Polyacrylamide Gel; hemorrhage; metalloproteinases; Mice; Monoclonal antibodies; Neutralization Tests; Neutralizing; octanoic acid; Phospholipase; phospholipase A2; polyacrylamide gel electrophoresis; Precipitation; Snake venom; Survival; survival rate; Toxicity; Toxicology; Toxins; venoms
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2013.05.005

Neutralizing monoclonal antibodies against three major toxic components of Bothrops atrox venom were produced and tested. The mAbs against phospholipase A2, hemorrhagic metalloprotease, and thrombin-like enzymes were produced in large amounts and purified with caprylic acid followed by ammonium sulfate precipitation. Purified mAbs were analyzed by SDS-PAGE and their ability to neutralize the respective toxins was tested. Five Swiss mice were injected i.p. with 13.5 mg of pooled mAbs and challenged via s.c. route with venom. Survival rate was recorded for the next 48 h. All mice treated and challenged with venom survived, whereas only one mouse in the control group survived. Bleeding time in mice treated with mAbs was similar to that observed in control mice. Our results show that monoclonal antibodies neutralized the lethal toxicity of Bothrops venom and indicate that there is a reasonable possibility of developing antivenoms based on humanized mAbs to treat victims of venomous animals in the future. •We used mAbs to neutralize Bothrops atrox venom toxic components.•Bleeding time was reduced in mice injected with mAbs and venom.•Pool of three mAbs protected mice challenged with venom.•Bothropic antivenom based on mAbs is supported by our data.