Serrumab: A human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom

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)-alpha, 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, TNF alpha, 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.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Instituto Nacional de Ciencia e Tecnologia em Toxinas (INCTTOX, Sao Paulo Research Foundation and National Institute of Toxin Science and Technology)

Instituto Nacional de Ciencia e Tecnologia em Toxinas (INCTTOX, Sao Paulo Research Foundation and National Institute of Toxin Science and Technology) [573790/2008-6]

Fundacao de Apoio ao Ensino, Pesquisa e Assistencia (FAEPA, Foundation for the Support of Instruction, Research and Treatment)

Fundacao de Apoio ao Ensino, Pesquisa e Assistencia (FAEPA, Foundation for the Support of Instruction, Research and Treatment)

Fundacao Waldemar Barhsley Pessoa (Waldemar Barhsley Pessoa Foundation)

Fundacao Waldemar Barhsley Pessoa (Waldemar Barhsley Pessoa Foundation)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Office for the Advancement of Higher Education)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Office for the Advancement of Higher Education)