Monoclonal antibody for passive immunotherapy treatment of Methicillin Resistant Staphylococcus Aureus (MRSA) infections of bone that occur following joint replacement surgeries.
GoalDiscovery and Development of Monoclonal Antibody for prophylactic and therapeutic treatment of MRSA Infections of Bone.
Relevance/MarketStaphylococcus aureus (SA), and Methicillin Resistant SA (MRSA)
in particular, have emerged as important and potentially devastating causes of post-operative infection following joint replacement surgery and fracture repair. The frequency of these orthopedic infections has been estimated at 2% for joint replacement surgery (which is performed annually in 600,000 Americans) and at 5% for implantation of fracture-fixation devices (which are used in some 2,000,000 Americans each year). Thus, the economic impact of these infections in profound, and projected at $360 million per year for joint replacement surgery, and roughly $1.5 billion per year for fracture repair.
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- A unique, quantitative mouse model of Staphylococcus aureus (SA)-associated osteomyelitis (OM) has been developed by Dr. Edward Schwarz and colleagues at the URMC Center for Musculoskeletal Research. This model has been used to identify a bacterial antigen that is the target of a protective humoral immune response.
- Monoclonal antibodies against this S. aureus antigen have been derived, and are being tested for their protective efficacy in the mouse model for SA-induced OM.
- GMP manufacture, safety/toxicity and early phase clinical trial analyses of protective antibodies are planned, to be followed by a pivotal clinical efficacy trial in the context of osteomyelitis.
- Competitive National Institutes of Health (NIH) funding for this project has been obtained, in the form of a Small Business Innovation Research (SBIR) award. Details can be found here.
High resolution electron micrograph images of Staph aureus.Image provided by Codevax and Dr. E.M. Schwarz, University of Rochester Medical Center.
MRSA References
Li, D., K. Gromov, K. Soballe, J.E. Puzas, R.J. O’Keefe, H. Awad, H. Drissi, and E.M. Schwarz. 2008. Quantitative Mouse Model of Implant-Associated Osteomyelitis and the Kinetics of Microbial Growth, Osteolysis, and Humoral Immunity. J Orthop Res 26:96-105
Varrone, J., D. Li, J. Daiss, and E.M. Schwarz. 2011 Anti-glucosaminidase Monoclonal Antibodies as a Passive Immunization for Methicillin-Resistant Staphylococcus aureus (MRSA) Orthopedic Infections. IBMS BoneKEy. 2011 April;8(4):187-194
Li, Dan. 2007. Development of a Quantitative Murine Model of Implant-associated Osteomyelitis and its use to Demonstrate the Adverse Effects of Anti-resorptive Drugs and Efficacy of an Immuno-dominant Antigen Vaccine on Staphylococcus aureus Infection of Bone. Department of Biomedical Genetics, School of Medicine and Dentistry, University of Rochester.
Acinetobacter baumannii
Once considered a minor clinical nuisance, Acinetobacter baumannii has recently been designated as one of the six so-called ‘ESKAPE’ bacterial pathogens of greatest healthcare concern by the Infectious Diseases Society of America. This dubious designation is attributable to the three alarming observations. First, the incidence of A. baumannii infections has dramatically increased in the U.S. and abroad. Once a rarity, A. baumannii now causes 3% of all hospital-acquired infections. Second, the severity of A. baumannii infections has increased dramatically. Outbreaks are often associated with high rates of morbidity and mortality (approximately 50%); in one extreme example, a neonatal intensive care unit outbreak led to 80% death. Third, the organism has developed resistance to all currently available antibiotics. Simply put, new therapeutic options are urgently needed for the intervention of Acinetobacter infections.
Codevax has therefore recently initiated a new program that aims to provide clinicians with new tools to combat hospital-acquired infections with multidrug-resistant Acinetobacter baumanii. This program seeks to develop a new passive immunization approach to the treatment of Acinetobacter infections, since we believe that this strategy will prove the most efficacious and be the most rapid to market. This prediction is based on the fact that A. baumannii has an enormous drug efflux potential, which enables otherwise susceptible strains to become antibiotic-tolerant, and is likely to limit the impact of new antibiotic development. Further, the most at-risk patient populations tend to have debilitated immune defenses that will make conventional vaccine approaches challenging.