Discovery of a Recombinant Human Monoclonal Immunoglobulin G Antibody Against α-Latrotoxin From the Mediterranean Black Widow Spider (Latrodectus tredecimguttatus)

Abstract

Widow spiders are among the few spider species worldwide that can cause serious envenoming in humans. The clinical syndrome resulting from Latrodectus spp. envenoming is called latrodectism and characterized by pain (local or regional) associated with diaphoresis and nonspecific systemic effects. The syndrome is caused by α-latrotoxin, a ~130 kDa neurotoxin that induces massive neurotransmitter release. Due to this function, α-latrotoxin has played a fundamental role as a tool in the study of neuroexocytosis. Nevertheless, some questions concerning its mode of action remain unresolved today. The diagnosis of latrodectism is purely clinical, combined with the patient’s history of spider bite, as no analytical assays exist to detect widow spider venom. By utilizing antibody phage display technology, we here report the discovery of the first recombinant human monoclonal immunoglobulin G antibody (TPL0020_02_G9) that binds α-latrotoxin from the Mediterranean black widow spider ( Latrodectus tredecimguttatus ) and show neutralization efficacy ex vivo . Such antibody can be used as an affinity reagent for research and diagnostic purposes, providing researchers with a novel tool for more sophisticated experimentation and analysis. Moreover, it may also find therapeutic application in future.

Terrestrial venomous animals, the envenomings they cause, and treatment perspectives in the Middle East and North Africa

“…Notably, a recombinant monoclonal antibody against α-Latrotoxin from the Mediterranean Black Widow Spider ( L . tredecimguttatus ) already exists, which has been shown to bind and neutralize this toxin ex vivo [ 231 ]. Supported by the comparatively small number of different toxins that require neutralization, the costly production of existing conventional antivenoms, and challenging maintenance of the venom supply chain, it thus is possible that the implementation of such recombinant therapeutics might first occur in spiders, likely followed by scorpions, and only then venomous snakes (due to the increasing complexity of their venoms).…”

Human antibodies neutralizing the alpha-latrotoxin of the European black widow

“…This could be explained due to the lower excess of antibody to α-LTX (10-fold molar excess of antibody to toxin in comparison to 50-fold molar excess of antibody to toxin in highest concentration of alamarBlue assay) and a higher assay sensitivity. The setup was purposely chosen to test for best neutralization efficacy, and to keep it comparable to other monoclonal α-LTX neutralizing antibody studies ( 59 ). Synergistic or additives effects of antibody combinations could not be confirmed.…”

“…Føns et al. described the first recombinant human IgG generated by phage display, which was also selected on L. tredecimguttatus α-LTX ( 59 ). The authors hypothesized that the antibody should be cross-neutralizing between Latrodectus species, due to the high-sequence identity of α-LTX.…”

Antibodies as Biosensors’ Key Components: State-of-the-Art in Russia 2020–2021

“…This is due to several restrictions in the development of the assay: (i) the complexity of reliable identification of the nature of a venom, (ii) the speed of assay execution due to the rapid propagation of venom in tissues, and (iii) high sensitivity of the assay, which is due to very low venom doses in bites and their rapid distribution in the blood [22]. A recently published work by a team of researchers from Denmark, Russia, and the United Kingdom [23] describes the production of α-latrotoxin recombinant human monoclonal immunoglobulin G antibody using a phage display library with primary scFv selection and its conversion to IgG. It was expressed in a HEK 293 cell line.…”