The Therapeutic Efficacy of MS473, a Fully Human Single-Chain Variable Fragment Targeting Staphylococcus aureus Toxic Shock Syndrome Toxin-1, in a D-Galactosamine-Sensitized Mouse Model of Lethal Shock.

Abstract

Toxic shock syndrome toxin-1 (TSST-1), produced by Staphylococcus aureus, is one of the most potent superantigens involved in causing life-threatening 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 per kg of mouse body weight) after five minutes or intravenously (3 mg per kg of mouse body weight) after 10 min. The survival rate was examined for seven days. Furthermore, blood samples from different groups of mice were subjected to biochemical assessment, and their kidneys and livers were analyzed histopathologically 24 h after the toxin injection. The findings demonstrated a 100% survival rate with no significant damage to kidney and liver function in the treated groups, receiving MS473 through two different administration routes compared to the control groups, including the toxin-injected mice receiving normal saline or an unrelated scFv. Targeting disseminated TSST-1 with the scFv, which has appropriate permeability and distribution throughout the body, may be an effective way to alleviate the malfunctioning of the immune system caused by TSST-1.