U19AI189176

IMMUNIZATION AGAINST MULTIDRUG-RESISTANT PATHOGENS: ACTIVATING T CELL IMMUNITY (IMPACT-CETR) - OVERALL PROJECT ABSTRACT THE OVERALL FOCUS OF THE “IMMUNIZATION AGAINST MULTIDRUG-RESISTANT PATHOGENS: ACTIVATING T CELL IMMUNITY” CENTER OF EXCELLENCE FOR TRANSLATIONAL RESEARCH (IMPACT-CETR) IS TO ADVANCE PROMISING MULTICOMPONENT VACCINES FOR STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, AND KLEBSIELLA PNEUMONIAE. THESE ARE AMONG THE MOST IMPORTANT BACTERIAL PATHOGENS THAT CAUSE SEVERE CLINICAL DISEASE AND DEATH AND YET ARE BECOMING INCREASINGLY RESISTANT TO THE MOST EFFECTIVE ANTIBIOTICS. THE OVERARCHING GOAL OF THIS IMPACT-CETR IS TO HARNESS THE COLLABORATIVE TEAM’S COMPLEMENTARY EXPERTISE IN IMMUNOLOGY, BACTERIOLOGY, BIOINFORMATICS, PRIMATOLOGY, VACCINE DEVELOPMENT, AND ANTIGEN-ADJUVANT FORMULATIONS TO ACHIEVE THREE DELIVERABLES: 1) NOVEL MULTICOMPONENT VACCINES OPTIMIZED FOR BACTERIAL PROTEINS AND/OR POLYSACCHARIDES THAT ELICIT BROAD AND POTENT SEROTYPE- INDEPENDENT PROTECTION AGAINST S. AUREUS, P. AERUGINOSA, AND K. PNEUMONIAE INFECTIONS, INCLUDING WITH RESISTANT AND MDR CLINICAL ISOLATES; 2) DEFINED KEY MECHANISMS OF HOST PROTECTION AND BIOMARKERS OF VACCINE EFFICACY; AND 3) NONHUMAN PRIMATE (NHP) MODELS TO CHARACTERIZE IMMUNOGENICITY AND SURROGATE MARKERS OF PROTECTION. THE PROPOSED VACCINE COMPONENTS ARE WELL-CHARACTERIZED, SOME ARE CHEMICALLY DEFINED, AND ALL ARE DESIGNED FOR FEASIBLE SCALE-UP AND MANUFACTURE. THE THREE RESEARCH PROJECTS IN THIS CETR ARE BONDED BY THE THEME THAT TISSUE-RESIDENT MEMORY T CELL RESPONSES, PARTICULARLY TISSUE-RESIDENT TH17 CELLS, ARE CRITICAL FOR PROTECTIVE VACCINES AGAINST THESE PATHOGENS. THE TRANSLATIONAL RESEARCH PROJECTS WILL DEVELOP COUNTERMEASURES TO PREVENT/REDUCE DISEASE CAUSED BY KEY RESISTANT AND MDR BACTERIAL PATHOGENS. PROJECT 1 ADDRESSES A MULTICOMPONENT S. AUREUS VACCINE FORMULATED WITH CONSERVED PROTEIN ANTIGENS USING THE NEW AND INNOVATIVE MULTIPLE ANTIGEN PRESENTING SYSTEM (MAPS) PLATFORM WHEREIN FUSION PROTEINS OF THE AVIDIN DERIVATIVE RHIZAVIDIN WITH CONSERVED S. AUREUS PROTEIN ANTIGENS ARE COMPLEXED TO A BIOTINYLATED POLYSACCHARIDE TO GENERATE PROTECTIVE B- AND T-CELLS. PROJECT 2 ADDRESSES A MULTICOMPONENT P. AERUGINOSA MAPS VACCINE BASED ON THE SEROTYPE- INDEPENDENT P. AERUGINOSA BIOFILM POLYSACCHARIDE PSL AND ITS CRITICAL LIPID EPITOPE, COMBINED WITH CONSERVED PROTEIN ANTIGENS INCLUDING THE TH17-ELICITING ANTIGEN POPB. PROJECT 3 ADDRESSES A QUADRIVALENT K. PNEUMONIAE VACCINE BASED ON CONSERVED PROTEINS THAT ELICIT PROTECTIVE TH17 CELLS AND ANTIBODIES. VACCINE CANDIDATES WILL BE TESTED IN WILD-TYPE AND TRANSGENIC AND/OR KNOCK-OUT MICE AND IN NON-HUMAN PRIMATES. THESE PROJECTS WILL BE SUPPORTED BY AN ADMINISTRATIVE CORE AND THREE SCIENTIFIC CORES THAT FOCUS ON BIOINFORMATICS, TRANSGENIC MOUSE MODELS FOR MECHANISTIC STUDIES, AND NHP STUDIES. THE EXPECTED MILESTONE FOR EACH PROJECT IS THE DEVELOPMENT OF A PRECLINICAL DATA PACKAGE THAT WOULD PAVE THE WAY FOR SUBSEQUENT IND APPLICATIONS AND CLINICAL TRIALS.

Children's Hospital Corporation

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Massachusetts United States

State-Wide

Centers of Excellence for Translational Research (CETR) (U19 Clinical Trial Not Allowed) (RFA-AI-23-065)