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.

• Antibodies
• monoclonal
• scorpion toxin
• single-chain antibodies
• sodium-channel toxin

Acknowledgments

The authors are grateful to Dr Ruth Verplaetse for help in data analysis. This study received financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo and Instituto Nacional de Ciência e Tecnologia em Toxinas (FAPESP and INCTTOX, São Paulo Research Foundation and National Institute of Toxin Science and Technology; Grant no. 573790/2008-6); the Fundação de Apoio ao Ensino, Pesquisa e Assistência (FAEPA, Foundation for the Support of Instruction, Research and Treatment); the Fundação Waldemar Barnsley Pessoa (Waldemar Barhsley Pessoa Foundation); and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Office for the Advancement of Higher Education), which provided a Programa de Doutorado no país com Estágio no Exterior (PDEE, Doctoral Study at Home/Fellowship Abroad Program) scholarship to MBP (Grant no. BEX 1095/11-0).