A BothropicAntivenom Based On Monoclonals Antibodies: Is It Possible?

Frauches, T.S., Escocard, R.C.M., Petretski, J.H., Lemos, L.S.², Carvalho, E.Q²;Diasda Silva, W., Kipnis, T.L., Kanashiro, M.M. 

Laboratório de Biologia do Reconhecer. Laboratório de Sanidade Animal. UENF. Campos dos Goytacazes-RJ, Brasil.

Since the development of serotherapy by A. Calmette in 1894 and its introduction in Brazil by V. Brazil in 1903, the parenteral administration of heterologous antibodies constitutes the cornerstone in the treatment of snakebite. Antivenoms contain antibodies to the majorities of the venom components or others specificities, which dilute the toxin-specific neutralizing antibodies. Neutralizing monoclonals antibodies produced against phospholipase A2 (clone A85/9), hemorrhagic metalloprotease (clone 59/2-E4) and thrombin-like (clone 6AD2-G5) enzymes purified from B. atrox venom were produced in large quantity, purified and tested to neutralize the respective toxin. Five CF1 mice (18-20g) were injected ip with 10.35 mg of pooled mAbs, followed by challenge with 200mg or 300mg of crude B. atrox venom through sc route and survival rate scored in 24 and 48 hours. In the group challenged with 200mg, 3 mice survived from 5, while in the control group (non-treated with mAbs mixture) 1 mouse survived. Histological analysis of survived mice showed a marked reduction of the lesions observed in lung, spleen, liver and heart of the animals treated with pooled mAbs in comparison to the control group. Kidney histological analysis showed a less severe lesion in non-treated group than in the group which received pooled mAbs. Altogether these results suggest that the development of a bothropic antivenom based on mAbs has a good future possibilty.

Support: CNPq, FAPERJ, UENF, TECNORTE

Correspondence to: kmilton@uenf.br