S. aureus Program
A Novel Paradigm for Fighting Staphylococcal Infections and Their Complications
The pathogenicity of Staphylococcus aureus (S. aureus) is dependent on a wide range of virulence factors including cell surface proteins, polysaccharides, and secreted toxins. Surface antigens mediate the attachment of the bacteria to the tissue, protect the bacteria from immune cells, and regulate the metabolic needs of the bacteria. S. aureus has an arsenal of secreted toxins that use a variety of mechanisms to cause tissue damage and thus promote bacterial dissemination and distant organ seeding. These toxins also inactivate or kill immune cells, such as phagocytic neutrophils, to evade the host immune response and to provide the bacteria with a growth advantage.
Lessons from prior failed efforts clearly show that an effective vaccine against S. aureus must be multivalent and importantly, must include attenuated toxin antigens. Using state of the art medicinal chemistry methods, IBT has designed and produced highly attenuated vaccines and antibody therapeutics for a variety of staphylococcal exotoxins and other relevant antigens including hemolysins (alpha and gamma toxin), leukocidins (such as PVL), and superantigens (SEB, SEA, TSST-1).
IBT's candidate vaccines have already demonstrated remarkable efficacy against S. aureus induced sepsis and pneumonia in mice and proof of concept studies in other models of staphylococcal infections are underway. A portfolio of patented intellectual property around these vaccine and immunotherapeutic candidates has been assembled to support continued development.
Recombinant staphylococcal enterotoxin (STEBVax) is IBT's prototype superantigen vaccine, currently (2013-2014) undergoing a Phase I clinical trial under an NIH sponsored program. STEBVax will be a component of a multivalent S. aureus vaccine, but also serves as a stand alone vaccine for protection of military and civilian populations against possible usage of this potent toxin in a biowarfare or bioterror attack.
Immunotherapeutic research at IBT focuses on the development of monoclonal antibodies, including bispecific and multispecific antibodies, that neutralize S. aureus toxins.
IBT is seeking partnership for advanced development of its multivalent toxoid vaccine and immunotheraputics.
Selected Publications
Structurally Designed Attenuated Subunit Vaccines for S. aureus LukS-PV and LukF-PV Confer Protection in a Mouse Bacteremia Model. Karauzum H, et al. PLoS One 2013; 8(6):e65384..
Structural model of the pre-pore ring-like structure of Panton-Valentine leukocidin: providing dimensionality to biophysical and mutational data. Aman MJ, et al. J Biomol Struct Dyn. 2010 Aug;28 (1):1-12.
Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB) protective against toxic shock syndrome. Karauzum H, et al. J Biol Chem. 2012 Jul 20;287(30):25203-15.
Novel structurally designed vaccine for S. aureus alpha hemolysin; protection against bacteremia and pneumonia. Adhikari RP, et al. PLoS One 2012; 7(6):e38567..
Lower Antibody levels to Staphylococcus aureus exotoxins are associated with sepsis in hospitalized adults with invasive S. aureus infections. Adhikari RP, et al. J Infect Dis. 2012 Sep 15;206(6):915-23.
Staphylococcal bicomponent pore-forming toxins: targets for prophylaxis and immunotherapy. Aman MJ, Adhikari RP. Toxins 2014; 6(3):950-972.