Abstract :
[en] Snake envenomation constitutes a major health concern across Africa, Middle-east, Asia, and subtropical regions with rural populations primarily affected. Each year, between 80 and 138 thousand fatalities occur from snakebite envenomation and three times as many people with disabilities even after treatment. Snake venom is a complex mixture of various peptides and proteins called toxins. These toxins induced different biological effects, such as paralysis, necrosis, and also haemorrhage, leading to potent fatality. The only treatment available for envenomation is Antivenom, which are serum containing Immunoglobulins G (IgGs) targeting venom toxins. These IgGs are purified from hyperimmunized horses or sheep blood. Even if antivenom undeniably saves several lives, it also provokes drawbacks. Indeed, the purified serums contain Toxin-specific IgGs but also IgGs from the immunogenic history of the animal. Unfortunately, these non-specific IgGs can trigger some severe adverse effects for people already at risk. In addition, Antivenoms are heat sensitive and are stored far from the targeted population. To address this public health concerns, the European ADDovenom project (2021-2024), funded by the European Commission (FET-Open), aims to develop a novel generation of antivenom based on ADDomers construct, ADDomers are thermally stable megadalton virus-like particles, produced at low cost and featuring 60 high-affinity binding sites.
The goal of this project is to develop new methodologies based on the use of magnetic beads allowing detection, quantification and characterization of the toxins recognized by the antivenom current antivenoms and by the ADDomers structures. For quantification, detection and characterization, LC-MS and tryptic digestion will be used. These new methods will also allow to unravel the complexity of antivenom by determining the percentage of toxins specific IgGs and their affinity constant using the native hold-up technique. All this using fewer critical compounds such as venom and antivenom in regards of the classical techniques.
