Analysis of camelid IgG for antivenom development: Immunoreactivity and preclinical neutralisation of venom-induced pathology by IgG subclasses, and the effect of heat treatment

被引:23
作者
Cook, Darren A. N. [1 ]
Samarasekara, Chamali L. [1 ]
Wagstaff, Simon C. [1 ]
Kinne, Joerg [2 ]
Wernery, Ulrich [2 ]
Harrison, Robert A. [1 ]
机构
[1] Univ Liverpool Liverpool Sch Trop Med, Alistair Reid Venom Res Unit, Liverpool L3 5QA, Merseyside, England
[2] Cent Vet Res Lab, Dubai, U Arab Emirates
基金
英国医学研究理事会;
关键词
Snake antivenom; Venom; Camelid IgG; Heavy chain IgG; Echis ocellatus; CAPRYLIC-ACID FRACTIONATION; MONOCLONAL-ANTIBODIES; CHAIN ANTIBODIES; FACTOR-VIII; SNAKE BITE; PASTEURIZATION; PLASMA; HORSE; VIRUSES; SERA;
D O I
10.1016/j.toxicon.2010.06.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Antivenom is the most effective treatment of snake envenoming and is manufactured from the IgG of venom-immunised horses and sheep Camelids have a unique IgG structure which may account for the report that camel IgG is less immunogenic and less likely to activate complement than equine or ovine IgG. Camelid IgG therefore offers potential safety advantages over conventional IgGs used for antivenom manufacture. The reported thermostability of camelid IgG also holds promise in the inclusion of a relatively inexpensive anti-microbial heat step in antivenom manufacture However, these potential benefits of camelid IgG would be much reduced if any one of the three camel IgG subclasses dominated, or under-performed, the serological response of camels to venom immunisation because of the prohibitive manufacturing costs of having to purify, or exclude, one or more IgG subclasses. This study compared the titre, antigen-specificity, relative avidity and ability to neutralise the haemorrhagic and coagulopathic effects of Edits ocellatus venom of each IgG subclass from the venom-Immunised camels. The results demonstrated that no one IgG subclass consistently out-performed or under-performed the others in their immunoreactivity to venom proteins and ability to neutralise venom-induced pathologies We concluded therefore that IgG taken from a pool of immunised camels could be processed into antivenom without requiring the implementation of expensive chromatographic separations to select, or Indeed to exclude, a specific IgG subclass. The immunoreactivity of the heavy and light chain. IgG1 subclass, was markedly more vulnerable to extreme heat treatment than the heavy chain-only IgG2 and IgG3 subclasses. (C) 2010 Elsevier Ltd All rights reserved
引用
收藏
页码:596 / 603
页数:8
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