This $208,332 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) supports research into the pathogenic mechanisms of Staphylococcus aureus spine infections. The key products and services to be delivered under this 5-year grant include: Clarifying the role of S. aureus surface proteins in promoting spine infection, and investigating how the immune evasion properties of these proteins...
This Project Grant from the National Science Foundation's Technology, Innovation, and Partnerships program totaling $295,247 will support the development of an innovative medical technology for localized and sustained antibiotic treatment of periprosthetic joint infection. Specifically, the awardee Reselute will design, develop, and validate a proof of concept for an orthopedic spacer implant with a novel porous medium capable of controlled antibiotic elution over 180 days. The implantable...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $208,154 to The General Hospital Corporation (doing business as Massachusetts General Hospital) to evaluate the potential of a novel Antimicrobial Blue Light (ABL) emitting envelope (ABL-ENV) to combat cardiac implantable electronic device (CIED) infections. The key products or services to be delivered under this award...
This National Science Foundation (NSF) Division of Materials Research Project Grant, CFDA# 47.049 Mathematical and Physical Sciences, provides $400,000 in funding to The Trustees of the University of Pennsylvania to conduct collaborative research on developing novel hybrid metal-piezoelectric biomaterials for anti-infectious implantable medical devices. The key objective is to create advanced multifunctional biomaterial platforms that can effectively prevent biofilm formation and bacterial...
This Project Grant award, valued at $231,700 and provided by the National Institute of Allergy and Infectious Diseases (CFDA 93.855 Allergy and Infectious Diseases Research), supports research to develop biologics that can block the agglutination of S. aureus bacteria with fibrin clots. The overall objective is to create novel therapeutic candidates for treating S. aureus infections, including antibiotic-resistant strains like MRSA. The research will 1) characterize the binding and...
This federal Project Grant award of $837,644, provided by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), aims to develop a comprehensive library of synthetic poly-β-(1-6)-N-acetylglucosamine (PNAG) oligosaccharides with systematically varied amine/acetylation patterns. These PNAG glycans will be conjugated to a mutant bacteriophage Qβ carrier and evaluated for their immunogenicity and protective efficacy...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $400,000 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) to Baylor College of Medicine in Houston, Texas. The funding will support pre-clinical studies to test the prophylactic efficacy of a potential vaccine against extraintestinal pathogenic E. coli (ExPEC), a member of the human microbiome that has become a leading cause of antibiotic-resistant mortality worldwide. The research...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $262,170 to The Leland Stanford Junior University (Stanford University) from August 1, 2024 to July 31, 2026. The award aims to develop a novel mucosal vaccine strategy that leverages the skin microbiota to induce precise and long-term immunity. The project will: 1) Uncover the B cell response to skin commensal...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), aims to study the mechanisms of biofilm formation by the bacteria Staphylococcus epidermidis on medically relevant surfaces. The key objectives are to: 1) Determine the structure and orientation of S. epidermidis proteins on polymethylmethacrylate (PMMA) surfaces, which are used in orthopedic and dental implants; 2) Develop a...
This federal Project Grant award of $918,400 from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 Allergy and Infectious Diseases Research) supports research at the University of Chicago to identify protective antigens and T/B cell responses against Staphylococcus aureus (S. aureus) infection. The goal is to exploit the observation that mice lacking the H2-O molecule, the equivalent of human HLA-DO, are able to efficiently decolonize S. aureus and resist subsequent...
BIOMATERIALS-BASED IMMUNOENGINEERING FOR PERIPROSTHETIC JOINT INFECTION - PROJECT SUMMARY / ABSTRACT DUE TO ADVANCES IN BIOMEDICAL ENGINEERING AND MEDICINE, JOINT REPLACEMENT HAS RESTORED FUNCTION AND RELIEVED PAIN FOR MILLIONS OF PEOPLE. HOWEVER, SUBSEQUENT INFECTION OF IMPLANTED JOINTS (KNOWN AS PERIPROSTHETIC JOINT INFECTION OR PJI) IS A DEBILITATING CONDITION THAT CAN LEAD TO MULTIPLE SURGERIES, LONG COURSES OF INTRAVENOUS ANTIBIOTICS, AND/OR LOSS OF LIMB OR EVEN LIFE. STAPHYLOCOCCUS AUREUS IS ONE OF THE MOST COMMON AND VIRULENT ORGANISMS THAT CAUSES PJI. S. AUREUS IS ALSO ASSOCIATED WITH SIGNIFICANT MORBIDITY AND FREQUENT RELAPSE FOLLOWING TREATMENT. VACCINATION AGAINST S. AUREUS IS A PROMISING STRATEGY TO PREVENT PERIPROSTHETIC JOINT INFECTION. HOWEVER, TRADITIONAL VACCINE SYSTEMS DESIGNED TO PREVENT S. AUREUS INFECTION HAVE FAILED IN CLINICAL TRIALS. THE GOAL OF THIS PROPOSAL IS TO EVALUATE A NOVEL APPROACH TO IMMUNOTHERAPY FOR S. AUREUS PJI BY ENGINEERING A BIOMATERIALS-BASED VACCINE PLATFORM (BIVAX). BIVAX IS AN INJECTABLE BIODEGRADABLE SCAFFOLD THAT ELUTES CYTOKINES TO RECRUIT DENDRITIC CELLS, CONTAINS ADJUVANT FOR ACTIVATION, AND IS LOADED WITH ANTIGEN AT HIGH CONCENTRATION FOR UPTAKE BY RECRUITED CELLS. OUR GROUP HAS PREVIOUSLY DEMONSTRATED THAT BY USING PATHOGEN- ASSOCIATED MOLECULAR PATTERNS AS ANTIGEN IN THIS BIOMATERIALS-BASED VACCINE SYSTEM, BIVAX IS EFFECTIVE AGAINST PREVENTING S. AUREUS ABSCESSES AND LETHALITY FROM SEPSIS DUE TO DIFFERENT GRAM-NEGATIVE SPECIES IN MOUSE MODELS. PJI IS A CHALLENGING BIOFILM-ASSOCIATED DEVICE INFECTION, AND IT IS UNKNOWN IF VACCINATION CAN PREVENT DISEASE. IN THIS PROPOSAL, I WILL EVALUATE THE EFFECTS OF INFECTION AND VACCINATION ON THE HOST IMMUNE RESPONSE AND DETERMINE THE EFFICACY OF BIVAX FOR PREVENTING PJI IN MURINE AND RABBIT MODELS OF DISEASE. I WILL DETERMINE HOST IMMUNE RESPONSES TO PJI AS A FUNCTION OF IMMUNITY AND PATHOGEN VIRULENCE FACTORS IN AIM 1 AND EVALUATE THE EFFECT OF BIVAX AGAINST PJI AND COMPARE ITS EFFICACY TO CONVENTIONAL VACCINATION STRATEGIES IN AIM 2. I AM SUPPORTED IN THESE EFFORTS BY WORLD EXPERTS IN IMMUNOTHERAPY, VACCINE SCIENCE, AND PJI INCLUDING: PRIMARY MENTOR DAVID MOONEY (IMMUNOENGINEERING); CO-MENTOR RUANNE BARNABAS (VACCINE SCIENCE), COLLABORATOR DAVID SCADDEN (STEM CELL BIOLOGY/IMMUNOLOGY); COLLABORATOR JEAN LEE (MURINE S. AUREUS VACCINATION); COLLABORATOR MICHAEL SUPER (IMMUNOLOGY AND GLYCOBIOLOGY); ADVISOR ANTONIA CHEN (ARTHROPLASTY AND HUMAN CLINICAL TRIALS FOR S. AUREUS VACCINES); ADVISOR SANDRA NELSON (CLINICAL PERIPROSTHETIC JOINT INFECTION); AND ADVISOR HANG LEE (BIOSTATISTICS). THE RESOURCE-RICH ECOSYSTEM OF MASSACHUSETTS GENERAL HOSPITAL, HARVARD UNIVERSITY, AND THE WYSS INSTITUTE FOR BIOLOGICALLY INSPIRED ENGINEERING HAVE AFFORDED ME THE NECESSARY TOOLS TO CONDUCT THIS MULTIDISCIPLINARY WORK AT THE INTERFACE OF BIOENGINEERING, MICROBIOLOGY, AND IMMUNOLOGY. THIS PROPOSAL INCLUDES A ROBUST TRAINING PLAN DESIGNED WITH MY MENTORS TO ACQUIRE ADDITIONAL SKILLS IN IMMUNOENGINEERING AND VACCINE SCIENCE NECESSARY FOR LAUNCHING AN INDEPENDENT CAREER INVESTIGATING IMMUNITY AT THE HOST/DEVICE/PATHOGEN INTERFACE IN DEVICE-RELATED INFECTION.