Superantigens

• Superantigens are toxins produced by commonly encountered staphylococcal and streptococcal bacteria.
• More than 40 divergent superantigens have been recognized to date.
• Superantigen toxins elicit a vastly exaggerated immune response, up to 50,000 times more potent than the response induced by ordinary antigens, resulting in a Th1 cytokine ‘storm’ that leads to toxic or septic shock.
• Death or incapacitation by natural mixtures of superantigen toxins constitutes an as yet unsolved medical problem as well as a bioterror threat; there is no available therapeutic nor a vaccine.
• Superantigens bypass the restricted presentation of conventional antigens, binding directly to the MHC class II molecule, the T cell receptor and an additional receptor discovered by Atox Bio's scientists.
• The subversion of the additional host receptor by superantigens may be employed more widely by pathogens.

Profound insight into the mechanism of superantigen action led to design of novel mechanism-based modulators of co-stimulatory signaling. This receptor is involved in different manifestations of disease: autoimmunity in its various forms, sepsis and toxic shock, as evidenced from animal studies.

Clinical utility of novel mechanism driven modulators of co-stimulation signal

• Treatment of acute diseases, by attenuating the Th1 cytokine storm:
• Gram-positive severe sepsis and septic shock – Results in mortality mediated through massive induction of Th1 cytokines, triggered by both Gram-negative and Gram-positive bacteria and their toxins.
• Avian influenza (H5N1) and swine influenza (H1N1) – Results in mortality mediated through massive induction of Th1 cytokines triggered by influenza virus.
• Toxic shock - Results from sudden and massive induction of Th1 cytokines produced by superantigen-stimulated immune cells.

• Treatment of chronic diseases mediated by excessive Th1 cytokine response:
• Autoimmune diseases – By attenuating the excessive Th1 cytokine response that lies at the core of the inflammatory response in each autoimmune disease, for example, in multiple sclerosis and rheumatoid arthritis.