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Principal Investigator: Brendan Joseph Kelly
Organization: UNIVERSITY OF PENNSYLVANIA
Fiscal Year: 2024
Award: $215,035
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY – CORE C (CLINICAL CORE)
Core C (Clinical Core) will support the overall mVACS program goal to develop modified mRNA vaccines to
eliminate C.difficile infection (CDI) by developing an infrastructure for CDI human subject identification, specimen
biobanking, and metadata collection to study the stool microbial ecology and C. difficile-specific adaptive immune
responses in humans. Core C (Clinical Core) will lead enrollment of patients, acquisition, storage, and
processing of specimens and associated clinical data in a biorepository and manage the distribution to individual
projects. In addition, longitudinal clinical outcomes will be followed after sample collection. We propose the
following specific aims: (1) to establish a recurrent CDI biorepository and clinical database, capturing stool
samples and demographic data at the time of diagnosis, across a range of ages and comorbidities; (2) to develop
a longitudinal cohort of CDI subjects enrolled at first disease recurrence, for in parallel deep microbial and
immune profiling, with linkage to longitudinal clinical outcomes; and (3) to provide samples and clinical metadata
from the established biorepository and cohort to allow testing and validation of in vitro and animal model findings
from Project 1 (Vaccine Development), Project 2 (Antigen Discovery), and Project 3 (Immunology). Core
C (Clinical Core) will facilitate correlation of clinical features of rCDI and its outcomes with findings in Project 1
(Vaccine Development), Project 2 (Antigen Discovery), and Project 3 (Immunology), as well as the genomic
findings in Core B (Genomics Core) in order to identify and refine vaccine targets that may increase efficacy.
Terms: <21+ years old><Academic Medical Centers><Adult><Adult Human><Affect><Age><Animal Model><Animal Models and Related Studies><Antigens><Assay><Bioassay><Biological Assay><Biological Specimen database><Bionomics><Blood Sample><Blood specimen><C diff><C difficile><C. diff><C. diff vaccine><C. difficile><C. difficile vaccine><Childhood><Children's Hospital><Circulatory Collapse><Clinical><Clinical Data><Clostridioides difficile><Clostridioides difficile vaccine><Clostridium difficile><Clostridium difficile vaccine><Colitis><Collaborations><Collection><Communities><Data><Development><Diagnosis><Disease><Disorder><Ecology><Elderly><Enrollment><Ensure><Feces><GI microbiota><Gastrointestinal microbiota><Genomics><Goals><Health system><Healthcare><Human><Hypotension><Ileus><Immune><Immune response><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><In Vitro><Incidence><Individual><Infection><Infection prevention><Infrastructure><Lead><Long-term cohort><Longitudinal cohort><Longterm cohort><Low Blood Pressure><Megacolon><Metadata><Microbe><Modern Man><Morbidity><Morbidity - disease rate><Operative Procedures><Operative Surgical Procedures><Outcome><Pb element><Pediatric Hospitals><Pediatric cohort><Pennsylvania><Philadelphia><Play><Population><Population Heterogeneity><Predictive Factor><Prevent infection><Public Health><R-Series Research Projects><R01 Mechanism><R01 Program><RNA vaccine><RNA-based vaccine><Recurrence><Recurrent><Recurrent disease><Relapsed Disease><Research Grants><Research Project Grants><Research Projects><Research Specimen><Risk><Risk Factors><Role><Sampling><Severities><Severity of illness><Shock><Specimen><Specimen Handling><Specimen Processing><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><Testing><Time><Universities><University Medical Centers><Vaccination><Vaccine Antigen><Vaccines><Validation><Vascular Hypotensive Disorder><Work><adaptive immune response><adulthood><advanced age><age group><ages><biobank><biorepository><biorepository database><biosample database><biospecimen database><circulatory shock><clinical database><clinical relevance><clinically relevant><co-morbid><co-morbidity><cohort><comorbidity><develop a vaccine><develop vaccines><development of a vaccine><developmental><disease severity><diverse populations><elderly patient><enroll><enteric microbial community><enteric microbiota><fecal microbial transplantation><fecal microbiome transplantation><fecal microbiota transplant><fecal microbiota transplantation><fecal sample><fecal transplant><fecal transplantation><gastrointestinal microbial flora><geriatric><gut commensal><gut community><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiota><gut microbiotic><gut microflora><health care><heavy metal Pb><heavy metal lead><heterogeneous population><host response><human subject><immune system response><immunization strategy><immunogen><immunoresponse><infection recurrence><innovate><innovation><innovative><intestinal flora><intestinal microbiota><intestinal microflora><intestinal tract microflora><mRNA vaccine><mRNA-based vaccine><meta data><microbial><microbial interaction><microorganism interaction><model of animal><mortality><new vaccines><next generation vaccines><novel><novel vaccines><older patient><participant enrollment><patient enrollment><patient population><pediatric><population diversity><prevent><preventing><programs><recurrent infection><recurring infection><risk mitigation><sample collection><senior citizen><shocks><social role><specimen collection><specimen database><stool><stool sample><stool specimen><success><surgery><vaccination strategy><vaccine development><vaccines against C . Difficile><vaccines against Clostridioides difficile><validations>