Because of their unique immune system, there has been a growing interest in recent years to assess the use of camelids for antivenom production. Aside from conventional IgGs, camelids have evolved a unique class of IgG naturally devoid of light chains called heavy-chain antibodies. The antigen binding sites of these HCAbs are composed of a single variable domain, and are the smallest natural antigen binding domain. HCAbs, and their VHHs, show particular promise for antivenom development because they can act as potent enzyme inhibitors by targeting cryptic enzyme clefts that are often poorly antigenic to mammalian immune systems that develop only conventional IgGs. Recent studies have shown that both camels and llamas immunized with snake venom generate antisera titres comparable to those of horses that are used for antivenom preparations. Encouraging results further show that camelid antibodies effectively neutralize the lethality and/or a variety of pathologies induced by snake venoms from Bothrops mattogrossensis; Echis ocellathus; and Bitis arietans. Further, scorpion venom toxins have been shown to be potently neutralized by specific camelid IgGs, HCAbs, and by monovalent or bivalent VHHs. While elapid venoms are generally considered poorly antigenic, one recent study showed potent camel antisera titres in response to Naja nigricollis immunization. Unfortunately, these camelid IgGs were not able to neutralize the lethal-effects of N. nigricollis envenomation in an in vivo mouse study. This last report indicates that more research needs to be done to increase our understanding of how to treat snake envenomation, particularly by elapids, using antibodybased products. Since conventional antivenom antibodies poorly neutralize venom toxins located in deep tissues, smaller recombinant antibody fragments, which are highly tissue permeable, have been explored in recent years for use in antivenom preparations. In fact, camelid VHHs have several attractive properties that may make them better therapeutic reagents for the treatment of snake envenomation: they are relatively non-immunogenic, soluble, stable, highly tissue penetrable and are easy to genetically BIBW2992 439081-18-2 manipulate for creation of multivalent/multifunctional formats. Nevertheless, antivenoms composed entirely of small antibody GDC-0199 Bcl-2 inhibitor fragments would likely have limited therapeutic efficacy because these fragments are cleared from the body rapidly. Therefore, it has been suggested in recent years that antivenoms prepared with a mixture of high molecular mass antibodies 2) and low molecular mass antibody fragments may offer better treatment for envenomation. This type of antivenom would not only allow the rapid neutralization of toxins by small fragments in tissue compartments, but also ensure that significant concentrations of antibodies 2) remain in circulation long enough to neutralize toxins there later in the course of envenomation. In recent years, members of the camelidae have been suggested for antivenom production. Similar to horses, camelids are docile and are able to yield large volumes of serum, and camel species are better suited than horses to live in hot, tropical and desert areas where snakes are most prevalent. In addition, camelid antibodies may represent a safer alternative to conventional equine and ovine antivenom antibodies because they are less immunogenic and therefore less likely to elicit adverse effects in patients. Further, camelid-derived single-domain antibody fragments possess several attractive physicochemical properties that may make them better therapeutic reagents for the treatment of envenomation. Due to their low molecular mass, VHHs penetrate tissue compartments more readily than conventional antibody fragments and, therefore, may protect victims from the tissue-damaging effects of venom toxins.