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

Abstract

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 Echis 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.