Bothropic antivenom based on monoclonal antibodies, is it possible?

被引：16

作者：

Frauches, Thiago S. ^{[1
]}

Petretski, Jorge H. ^{[1
]}

Arnholdt, Andrea C. V. ^{[1
]}

Lasunskaia, Elena B. ^{[1
]}

de Carvalho, Eulogio C. Q.

Kipnis, Thereza L. ^{[1
]}

da Silva, Wilmar D.

Kanashiro, Milton M. ^{[1
]}

机构：

[1] Univ Estadual Norte Fluminense, Ctr Biociencias & Biotecnol, Lab Biol Reconhecer, BR-28013602 Campos Dos Goytacazes, RJ, Brazil

来源：

TOXICON | 2013年 / 71卷

基金：

巴西圣保罗研究基金会;

关键词：

Monoclonal antibodies; Antivenom; Bothrops atrox; Snake venom; PHOSPHOLIPASES A(2); SNAKE-VENOM; PROTEINS; ASPER;

D O I：

10.1016/j.toxicon.2013.05.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Neutralizing monoclonal antibodies against three major toxic components of Bothrops atrox venom were produced and tested. The mAbs against phospholipase A(2), 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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：49 / 56

页数：8

共 37 条

[11] CHIPPAUX JP, 1991, B SOC PATHOL EXOT, V84, P286
[12] Evaluation of three Brazilian antivenom ability to antagonize myonecrosis and hemorrhage induced by Bothrops snarce venoms in a mouse model
da Silva, Noelson M. V.
Arruda, Emerson Z.
Murakami, Yugo L. B.
Moraes, Raphael A. M.
El-Kik, Camila Z.
Tomaz, Marcelo A.
Fernandes, Fabricio F. A.
Oliveira, Clayton Z.
Soares, Andreimar M.
Giglio, Jose R.
Melo, Paulo A.
[J]. TOXICON, 2007, 50 (02) : 196 - 205
[13] Chemical modification of histidine and lysine residues of myotoxic phospholipases a, isolated from Bothrops asper and Bothrops godmani snake venoms: Effects on enzymatic and pharmacological properties
DiazOreiro, C
Gutierrez, JM
[J]. TOXICON, 1997, 35 (02) : 241 - 252
[14] FUNASA, 2001, MAN DIAGN TRAT AC AN, P1
[15] Towards a standardization of the murine tail bleeding model
Greene, T. K.
Schiviz, A.
Hoellriegl, W.
Poncz, M.
Muchitsch, E. -M.
[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2010, 8 (12) : 2820 - 2822
[16] Skeletal muscle degeneration induced by venom phospholipases A2:: insights into the mechanisms of local and systemic myotoxicity
Gutiérrez, JM
Ownby, CL
[J]. TOXICON, 2003, 42 (08) : 915 - 931
[17] Research strategies to improve snakebite treatment: Challenges and progress
Harrison, Robert A.
Cook, Darren A.
Renjifo, Camila
Casewell, Nicholas R.
Currier, Rachel B.
Wagstaff, Simon C.
[J]. JOURNAL OF PROTEOMICS, 2011, 74 (09) : 1768 - 1780
[18] Engineered antibody fragments and the rise of single domains
Holliger, P
Hudson, PJ
[J]. NATURE BIOTECHNOLOGY, 2005, 23 (09) : 1126 - 1136
[19] IBGE - Instituto Brasileiro de Geografia e Estatistica, 2004, CENS DEM 2004
[20] KAMIGUTI AS, 1992, THROMB HAEMOSTASIS, V67, P484

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