Therapeutic Human Hyperimmune Polyclonal Antibodies against Staphylococcal Enterotoxin B

Research Proposed: Determine the feasibility of developing human hyperimmune serum (HIS) against staphylococcal enterotoxin B (SEB). PROBLEM/OPPORTUNITY: Staphylococcus aureus is associated with up to 25% of invasive infections in hospitals and community. Staphylococcal exotoxins (SEs), including SEB, are key virulence factors leading to toxic shock syndrome (TSS). SEB has been weaponized and can cause human incapacitation and mortality. No countermeasures targeting SEs are currently available for human use. Integrated BioTherapeutics (IBT) has a cGMP produced SEB vaccine (STEBVax; currently in IND process) that may be used to generate HIS to treat SEB intoxication. PLAN/PROCESS OUTLINE: Screen human intravenous immunoglobulin and monkey immune sera and use, as HIS surrogates to develop assays and SOPs to test sera for inhibition of superantigenic activity. Evaluate neutralizing activity of antibodies in vitro (>80% inhibition) and in mice (>80% protection). PHASE I OPTION: Develop a clinical protocol for plasmapheresis of volunteers vaccinated with STEBVax. PHASE II PLAN: IBT plans for a cost shared phase II to conduct plasmapheresis for collection of anti-SEB HIS in partnership with Omrix Biopharmaceuticals, a leading plasma fractionation company, using the IND status of STEBvax and preclinical evaluation of anti-SEB HIS in anticipation of filing an IND with FDA.