Insect larvae as Biofactories to produce sphingomyelinase D for Loxosceles antivenom development

MC CALLUM GREGORIO; IGNACIO SMITH; BIRENBAUM, JOAQUÍN MANUEL; MARÍA SOL RODRIGUEZ; DOKMETJIAN CHRISTIAN; CASCONE OSVALDO; DE ROODT ADOLFO; MATIAS FINGERMANN; MARÍA VICTORIA MIRANDA

Congreso; The 2nd International Electronic Conference on Toxins; 2023

Loxosceles species, commonly named “violin” spiders, are widely spreadvenomous spiders. Clinical cases of Loxosceles bites are more commonlyreported in the Americas, particularly in Argentina, Brazil, Chile and Perú. Mostaccidents are characterized by dermonecrotic lesions, often referred to asnecrotic or gangrenous arachnidism. However, in about 10% of the cases a moreserious presentation occurs, characterized by a systemic evolution of thepathology that can result in a fatal outcome, mostly in children and elders.Antivenom against Loxosceles species is being produced in the Americas sincethe early 1960s. Its Active Pharmaceutical Ingredients are immunoglobulins ortheir fragments obtained from equine plasma of animals hyperimmunized withspiders’ venom. Venom extraction, a very laborious task with very low yields perspider, is the most relevant production bottleneck. Herein we optimized abiotechnological process based on Spodoptera frugiperda larvae as biofactoriesto obtain a recombinant version from L. laeta sphingomyelinase D (rSmase). TherSmase was recovered high purity level (94.5%) in one-chromatographic step atlow cost. Our version of rSmase was able to induce a neutralizing humoralresponse in horses’ sera. The amount of venom of 17000 spiders could bereplaced with rSmase from 1600 insect larvae. The use of rSmase is expected tochange traditional antivenom production.