The Therapeutic Efficacy of MS473, a Fully Human Single-Chain Variable Fragment Specific to Staphylococcus aureus Toxic Shock Syndrome Toxin-1, in a Mouse Model of Toxic Shock

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Abstract Toxic shock syndrome toxin-1 (TSST-1), produced by Staphylococcus aureus, is one of the most potent superantigens involved in causing life-threatening toxic shock syndrome (TSS) and contributes to the onset of some autoimmune diseases. To this end, we have previously identified a fully human single-chain variable fragment antibody (scFv), MS473, exhibiting high binding affinity and specificity for TSST-1 and demonstrating in vitro neutralization activity. In the present study, the therapeutic activity of MS473 was assessed in a D-galactosamine-sensitized mouse model of lethal shock. D-galactosamine-sensitized mice were injected with TSST-1 and then received a single dose of MS473 intraperitoneally (15 mg/kg) after five minutes or intravenously (3 mg/kg) after 10 minutes. The survival rate was examined for seven days. Furthermore, mice were killed after 24 hours, and their kidneys and liver were histopathologically examined. The findings demonstrated a 100% survival rate and no significant pathology damage on tissue samples in both treated groups, administered with MS473 in two different routes compared to the control groups, including toxin-injected mice receiving normal saline or an unrelated scFv. Targeting disseminated TSST-1 with scFvs, which have appropriate permeability and distribution throughout the body, may be an effective way to alleviate the malfunctioning of the immune system caused by TSST-1.