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Anti-Autolysin Passive Immunity for MRSA Osteomyelitis

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
95747
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
AI085844
Solicitation Year:
N/A
Solicitation Topic Code:
NIAID
Solicitation Number:
N/A
Small Business Information
CODEVAX, INC.
157 GLEN ELLYN WAY ROCHESTER, NY 14618-1516
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: Anti-Autolysin Passive Immunity for MRSA Osteomyelitis
Agency: HHS
Contract: 1R43AI085844-01A1
Award Amount: $326,193.00
 

Abstract:

DESCRIPTION (provided by applicant): Recently methicillin resistant Staphylococcus aureus (MRSA) has surpased HIV as the most deadly pathogen in the United States, accounting for over 100,000 deaths per year. In Orthopaedics, MRSA osteomyelitis (OM) has b ecome the greatest concern in patient care, desite the fact that improvements in surgical technique and aggressive antibiotic prophylaxis have decreased the infection rate for most procedures to less than 1-5%. In order to better understand pathogen-host i nteractions during the establishment of OM, develop new interventions and an effective diagnostic, we have developed a novel murine model of implant- associated OM in which a stainless steel pin is coated with S. aureus and implanted transcortically throug h the tibial metaphysis. This leads to a highly reproducible infection with osteolysis by day 9, fractures within three weeks, and closely resembles clinical OM around an external fixation pin. Furthermore, we have developed real time quantitative-PCR (RTQ -PCR) to determine nuc gene copy number in infected bone tissue, which is accurate to ~100 copies; and in vivo bioluminescence imaging to quantify the bacterial load longitudinally. We used this model to clone the glucosaminidase subunit of autolysin as an immuno-dominant antigen and demonstrated its potential as an active vaccine. However, as the target populations for this vaccine are immuno-compromised or elderly patients, Codevax LLC has initiated development of a passive immunization that can be given to high-risk patients prior to surgery. Currently, the company has 13 monoclonal antibodies against glucosaminidase that it needs to screen to derive a primary, secondary and tertiary candidate for clinical trials based on their ability to: 1) bind an e pitope within a highly concerned domain (100%amino acid identity of all know S. aureus strains) with high affinity (lt 10-9M; 2); 2) mediate enzyme inhibition, cytostasis or cytolysis of the bacteria in vitro; and 3) significantly protect mice from implant associated OM. Here we propose the pivotal experiments to test these mAbs accordingly, and derive the candidates to be developed as the first passive immunization for MRSA. PUBLIC HEALTH RELEVANCE: Anti-Autolysin Passive Immunity for MRSA Osteomyeliti s Methicillin resistant Staphylococcus aureus (MRSA) has surpased HIV as the most deadly pathogen in the United States, accounting for over 100,000 deaths per year. In Orthopaedics, MRSA osteomyelitis (OM) has become the greatest concern in patient care. To address this need, Codevax, Inc. aims to develop the first passive immunization to prevent MRSA infections in patients undergoing total joint replacement surgery.

Principal Investigator:

John L. Daiss
5853831636
JDAISS@ROCHESTER.RR.COM

Business Contact:

Stephen Dewhurst
Small Business Information at Submission:

CODEVAX, INC.
CODEVAX, INC. 157 GLEN ELLYN WAY ROCHESTER, NY 14618

EIN/Tax ID: 126291399
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No