title: Serrumab: a human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom.
abstract: In Brazil, the species Tityus serrulatus is responsible for the most severe cases of scorpion envenomation. There is currently a need for new scorpion anti-venoms that are more effective and less harmful. This study attempted to produce human monoclonal antibodies capable of inhibiting the activity of T. serrulatus venom (TsV), using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Four rounds of phage antibody selection were performed, and the round with the highest phage antibody titer was chosen for the production of monoclonal phage antibodies and for further analysis. The scFv 2A, designated serrumab, was selected for the production and purification of soluble antibody fragments. In a murine peritoneal macrophage cell line (J774.1), in vitro assays of the cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were performed. In male BALB/c mice, in vivo assays of plasma urea, creatinine, aspartate transaminase, and glucose were performed, as well as of neutrophil recruitment and leukocyte counts. It was found that serrumab inhibited the TsV-induced increases in the production of IL-6, TNFα, and IL-10 in J774.1 cells. The in vivo inhibition assay showed that serrumab also prevented TsV-induced increases in the plasma levels of urea, creatinine, aspartate transaminase, and glucose, as well as preventing the TsV-induced increase in neutrophil recruitment. The results indicate that the human monoclonal antibody serrumab is a candidate for inclusion in a mixture of specific antibodies to the various toxins present in TsV. Therefore, serrumab shows promise for use in the production of new anti-venom.
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, Brazil.
authors.forename: Manuela Berto
authors.initials: MB
authors.lastname: Pucca
authors.forename: Karina Furlan
authors.initials: KF
authors.lastname: Zoccal
authors.forename: Eduardo Crosara
authors.initials: EC
authors.lastname: Roncolato
authors.forename: Thaís Barboza
authors.initials: TB
authors.lastname: Bertolini
authors.forename: Lucas Benício
authors.initials: LB
authors.lastname: Campos
authors.forename: Camila Takeno
authors.initials: CT
authors.lastname: Cologna
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
authors.forename: Eliane Candiani
authors.initials: EC
authors.lastname: Arantes
authors.forename: José Elpidio
authors.initials: JE
authors.lastname: Barbosa
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use; D000997:Antivenins / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D019151:Peptide Library; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000633:toxicity; D012605:Scorpions / Q000502:physiology*; D057127:Single-Chain Antibodies / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000997:Antivenins; D016207:Cytokines; D019476:Insect Proteins; D019151:Peptide Library; D012604:Scorpion Venoms; D057127:Single-Chain Antibodies; C120263:scorpion toxin Ts1, Tityus; C000593859:serrumab