Serrumab: A novel human single chain-fragment antibody with multiple scorpion toxin-neutralizing capacities

Abstract

In Brazil, scorpion envenomation is an important public health problem. The yellow scorpion, Tityus serrulatus (Ts), is considered the most dangerous species in the country, being responsible for the most severe clinical cases of envenomation. Currently, the administration of serum produced in horses is recognized and used as a treatment for accidents with scorpions. However, horse herds' maintenance is costly and the antibodies are heterologous, which can cause anaphylaxis and Serum Sickness. In the present work, a human monoclonal fragment antibody, Serrumab, has been analysed. Toxin neutralizing effects of Serrumab were evaluated using a two-electrode voltage-clamp technique. The results show that Serrumab presented a high neutralizing effect against Ts β-toxins (Ts1, 43.2% and Ts2, 68.8%) and none or low neutralizing effect against α-toxins (Ts3, 0% and Ts5, 10%). Additional experiments demonstrated that Serrumab was also able to neutralize the action of toxins from other scorpion genus (Css II, 45.96% and Lqh III, 100%/β- and α-toxins, respectively). This work indicated that Serrumab is able to neutralize many toxins in Ts venom, and could being considered as a neutralizing antibody for formulating a human anti-scorpion serum in Brazil. Additionally, this work demonstrated that Serrumab could neutralize different toxins from distinct scorpion genus. All these results reinforce the idea that Serrumab is a scFv antibody with multiple neutralizing capacities and a promising candidate for inclusion in scorpion anti-venoms against different genera.

Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential

“…Two research groups independently isolated scFvs that recognize toxins from the Tityus serrulatus venom, and in both cases, this was carried out after panning human naive libraries [70,71,72]. By opting for this strategy, researchers avoided long-term animal immunization protocols and focused on the expected lack of immunogenicity of human-derived molecules.…”

Basics of Antibody Phage Display Technology

“…One obtained scFv was investigated for its neutralizing abilities both through in vitro biochemical assays and in a murine model, where it showed partially neutralizing effects. In a later study of the same scFv, it was additionally shown that the scFv could neutralize the effects of similar β-neurotoxins from other scorpion genera [ 58 ].…”

Isolation and characterization of Ts19 Fragment II, a new long-chain potassium channel toxin from Tityus serrulatus venom

“…Immersion in tricaine solution (1 g/L) was the anesthetic method used to induce anesthesia. The frog procedure was as previously used [7,21,24,31].…”