Rochester General Hospital

NTHI IMMUNITY IN YOUNG CHILDREN

A PHASE II STUDY EVALUATING THE SAFETY AND EFFICACY OF WHOLE-CELL PNEUMOCOCCAL VACCINE (WSP) IN REDUCING NASOPHARYNGEAL COLONIZATION BY STREPTOCOCCUS PNEUMONIAE IN YOUNG CHILDREN - ABSTRACT. WHILE NEW, HIGHER-VALENCY PNEUMOCOCCAL CONJUGATE VACCINES( PCVS), PCV15 AND PCV20, WILL INCLUDE IMPORTANT SEROTYPES, THEIR IMPACT AND COST-EFFECTIVENESS WILL LIKELY BE LESS THAN WHAT WAS ACHIEVED WITH INTRODUCTION OF PCV7, PCV10 AND PCV13 BECAUSE, IN RECENT YEARS, PREVALENT SEROTYPES CAUSING INFECTIONS HAVE CHANGED AND CONTINUE TO CHANGE. HERE WE PROPOSE A CLINICAL STUDY, VACCINATING CHILDREN WITH A LOW COST-TO-PRODUCE, SEROTYPE-INDEPENDENT, KILLED, NON-CAPSULATED AVIRULENT WHOLE-CELL STREPTOCOCCUS PNEUMONIAE (WSP) VACCINE THAT ELICITS TH17 CELL-MEDIATED IMMUNITY AND ANTIBODIES AGAINST ALL PNEUMOCOCCAL SEROTYYPES, AND WHICH HAS BEEN TESTED IN ADULTS AND TODDLERS. NASOPHARYNGEAL (NP) COLONIZATION IS A PREREQUISITE TO PNEUMOCOCCAL DISEASES AND TRANSMISSION. WE WILL EVALUATE THE EFFICACY OF WSP VACCINATION IN YOUNG CHILDREN ON PNEUMOCOCCAL NP COLONIZATION AT TIMES OF HEALTH AND ONSET OF ACUTE OTITIS MEDIA. NOTABLY, PREVENTION OF PNEUMOCOCCAL NP COLONIZATION MAY BE A SURROGATE FOR PREVENTION BY WSP OF PNEUMOCOCCAL INFECTIONS. IN ADDITION, WE WILL CONFIRM THE SAFETY AND IMMUNOGENICITY OF WSP. DEMONSTRATION OF A REDUCTION OF NP COLONIZATION, SAFETY, IMMUNOGENICITY OF WSP WOULD ENGAGE THE SCIENTIFIC AND PUBLIC HEALTH COMMUNITY AND COMMERCIALIZATION SUPPORT FOR ADDITIONAL LICENSURE STUDIES TO NEXT TEST FOR PROTECTION AGAINST VARIOUS PNEUMOCOCCAL DISEASES, TO DETERMINE WHETHER WSP COULD COMPLEMENT PCVS OR EVEN REPLACE PCVS AS AN INEXPENSIVE, SEROTYPE-INDEPENDENT VACCINE.

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - NON-CONSTRUCTION - ROCHESTER GENERAL HOSPITAL COLLEGE OF HEALTH CAREERS WILL USE FUNDING FOR STUDENT SCHOLARSHIPS FOR LPN AND RN STUDENTS, AS WELL AS CREATE A SIMULATION LAB AND EXPANDED CLASSROOM SPACE FOR THESE VITAL NURSING TRAINING PROGRAMS.

HAEMOPHILUS INFLUENZAE LIPOPROTEIN FUSION VACCINE AND LIPOPROTEIN VACCINE PLATFORM DEVELOPMENT - ABSTRACT: A VACCINE TO PREVENT NONTYPEABLE HAEMOPHILUS INFLUENZAE (NTHI) INFECTIONS IS A MAJOR UNMET NEED. NTHI CAUSES RESPIRATORY INFECTIONS IN CHILDREN AND ADULTS INCLUDING ACUTE OTITIS MEDIA (AOM), ACUTE SINUSITIS, CONJUNCTIVITIS, ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), NEUTROPHILIC ASTHMA AND INVASIVE DISEASE THAT LEADS TO HIGH MORBIDITY AND MORTALITY WORLDWIDE. PREVIOUSLY WE HAVE SHOWN LIPIDATION OF PROTEINS P6 AND OMP26 OF NTHI ENHANCES ANTIBODY AND TH17 IMMUNITY AND PROVIDES PROTECTION AGAINST NASOPHARYNGEAL (NP) COLONIZATION AND EAR INFECTION CAUSED BY NTHI COMPARED TO NON-LIPIDATED CONSTRUCTS. IN THIS PROJECT, WE WILL EVALUATE IMMUNOGENICITY AND PROTECTIVE EFFICACY OF NTHI LIPIDATED PROTEIN D AND PROTEIN F AND THEIR FUSION CONSTRUCTS VERSUS THEIR NON-LIPIDATED CONSTRUCTS AFTER SYSTEMIC VACCINATION IN A MOUSE MODEL OF NP COLONIZATION, EAR AND LUNG INFECTION. WE EXPECT OUR NOVEL LIPIDATED AND FUSION CONSTRUCTS TO ENHANCE SERUM AND MUCOSAL IGG ANTIBODY AND ACTIVATE TH17- MEDIATED IMMUNITY IN NASAL ASSOCIATED LYMPHOID TISSUE (NALT) ALONG WITH GENERATING T-CELL RESIDENT MEMORY (TRM) AGAINST NTHI. DIFFERENTIAL EFFECTS OF DIACYL VS TRIACYL VARIATION OF A LIPID MOIETY IN STIMULATION OF TLR2/TLR1 VS. TLR2/TLR6 WILL BE DETERMINED. WE HAVE SYNTHESIZED AND WILL TEST A QUADRIVALENT (L-OMP26ΦNL-P6ΦNL-PDΦNL-PF) FUSION (TRUNCATED VERSION OF EACH PROTEINS BASED ON THEIR FUNCTIONAL EPITOPES) MAKING ONLY ONE PROTEIN LIPIDATED ANTICIPATING ENHANCED IMMUNOGENICITY FOR ALL 4 PROTEINS. OVERALL THE PROJECT WILL EXPAND OUR UNDERSTANDING OF IMMUNE MECHANISMS ACTIVATED BY NOVEL LIPOPROTEIN NTHI FUSION VACCINE CONSTRUCTS AND IDENTIFY ANY DIFFERENCES IN IMMUNE RESPONSE ASSOCIATED WITH DIACYL VS. TRIACYL LIPIDATION (TLR2/TLR1 VS. TLR2/TLR6 ACTIVATION) ON PROTECTIVE EFFICACY AGAINST NTHI NP COLONIZATION, EAR AND LUNG INFECTION. THIS PROJECT WILL MORE BROADLY INNOVATE WITH A NOVEL LIPOPROTEIN VACCINE PLATFORM THAT MAY BE APPLIED TO OTHER PATHOGENS AND VACCINE CANDIDATE PROTEINS (INCLUDING THOSE THAT ARE NOT NATURALLY LIPIDATED) WHERE MUCOSAL COLONIZATION IS THE FIRST STEP OF PATHOGENESIS.

ROCHESTER REGIONAL HEALTH LOGISTICS HUB - ROCHESTER REGIONAL HEALTH WILL USE FEDERAL FUNDING TO SUPPORT THE ROCHESTER REGIONAL HEALTH LOGISTICS HUB, A CENTRALIZED TRANSPORTATION AND LOGISTICS COMMAND CENTER DESIGNED TO MODERNIZE HOW PATIENTS, MEDICATIONS, MEDICAL SUPPLIES, AND LAB SPECIMENS MOVE ACROSS ROCHESTER REGIONAL HEALTH'S URBAN AND RURAL SERVICE AREAS ACROSS NEW YORK STATE. THE PROJECT WILL PURCHASE MOVEABLE EQUIPMENT, INCLUDING TWO AMBULANCES, TWO WHEELCHAIR/STRETCHER-ACCESSIBLE VANS, AS WELL AS FURNITURE AND TECHNOLOGY TO SUPPORT REAL-TIME COORDINATION AND DAILY HUB OPERATIONS. THE LOGISTICS HUB WILL IMPROVE PATIENT CARE BY REDUCING DELAYS IN MEDICAL TRANSFERS, STRENGTHENING EMERGENCY RESPONSE CAPACITY, AND ENSURING THAT RURAL HOSPITALS AND CLINICS RECEIVE CRITICAL MEDICATIONS, SUPPLIES, AND LAB SPECIMENS MORE EFFICIENTLY. BY REPLACING FRAGMENTED, MANUAL, AND AD HOC TRANSPORTATION PROCESSES WITH A CENTRALIZED LOGISTICS MODEL, ROCHESTER REGIONAL HEALTH WILL REDUCE INEFFICIENCIES, LOWER TRANSPORTATION COSTS, IMPROVE SUPPLY CHAIN RELIABILITY, AND SUPPORT TIMELY ACCESS TO SPECIALTY CARE ACROSS THE FINGER LAKES AND NORTH COUNTRY REGIONS. THIS INVESTMENT WILL BENEFIT THE COMMUNITY BY IMPROVING HEALTHCARE ACCESS FOR RURAL RESIDENTS, REDUCING UNNECESSARY DELAYS AND COSTS, AND STRENGTHENING THE RESILIENCE OF NEW YORK’S HEALTHCARE INFRASTRUCTURE.

INSTITUTIONAL SUPPORT FOR COVID-19 RELIEF FOR THE ISABELLA GRAHAM HART SCHOOL OF PRACTICAL NURSING AT ROCHESTER GENERAL HOSPITAL.

THE NETWORK BIOLOGY OF PATHOGEN-HOST INTERACTIONS DRIVING EXACERBATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

SUPPORT FOR STUDENTS OF THE ISABELLA GRAHAM HART SCHOOL OF PRACTICAL NURSING.

ENHANCED IMMUNOGENICITY AND PROTECTION STUDY OF LIPID MODIFIED PROTEIN VACCINE CANDIDATES OF NONTYPEABLE HAEMOPHILUS INFLUENZAE

HEALTH CARE AND OTHER FACILITIES

AFFORDABLE CARE ACT (ACA) GRANTS FOR SCHOOL-BASED HEALTH CENTERS CAPITAL PROGRAM

AFFORDABLE CARE ACT (ACA) GRANTS FOR SCHOOL-BASED HEALTH CENTERS CAPITAL PROGRAM

ADDITIONAL SUPPORT FOR THE ISABELLA GRAHAM HART SCHOOL OF PRACTICAL NURSING DUE TO COVID-19.

ANALYSIS OF PRO-INFLAMMATORY MEMORY CD4 T-CELL SUBSETS TO INFLUENZA INFECTION

RECENTLY ARRIVED REFUGEES

HEALTH CARE AND OTHER FACILITIES

INNATE IMMUNE CELL SUBTYPES INVOLVED IN INFANT RESPONSES TO PROTEIN-CONJUGATE AND WHOLE-CELL PNEUMOCOCCAL VACCINES. - PROJECT SUMMARY/ABSTRACT: STREPTOCOCCUS PNEUMONIAE IS A LEADING KILLER OF INFANTS THROUGHOUT THE WORLD. WHILE A CONJUGATED VACCINE (INVENTED BY MEMBERS OF THE MENTORSHIP TEAM ON THIS APPLICATION) HAS ENABLED SUCCESSFUL VACCINATION OF INFANTS, NOT ALL INFANTS MOUNT A PROTECTIVE RESPONSE TO VACCINATION. 1 IN 9 CHILDREN DO NOT MOUNT PROTECTIVE RESPONSES TO HALF OF THE VACCINES IN THEIR PRIMARY SERIES. THIS WORK WILL DEFINE WHY THIS IS OCCURRING. STUDIES IN ADULTS SHOWED THAT AN ELEVATED FREQUENCY OF NATURAL KILLER (NK) CELLS IS ASSOCIATED WITH LOW PNEUMOCOCCAL VACCINE RESPONSES. IN CONTRAST, ADULT VACCINE TRIALS FOUND AN ELEVATED FREQUENCY OF INFLAMMATORY ANTIGEN PRESENTING CELLS (APCS) WAS ASSOCIATED WITH HIGHER VACCINE RESPONSES. THIS WORK WILL TEST THE HYPOTHESIS THAT INFANTS WITH LOW VACCINE RESPONSES TO PNEUMOCOCCAL VACCINES HAVE HIGH NK CELL FREQUENCY AND FUNCTIONALITY AND LOW INFLAMMATORY APC FREQUENCY WITH IMPAIRED FUNCTIONALITY. THIS WORK COMPARES THE ROLE OF THESE POPULATIONS IN RESPONSES TO THE LICENSED CONJUGATED VACCINES AND A KILLED WHOLE-CELL STREPTOCOCCUS PNEUMONIAE VACCINE BEING TESTED IN US INFANTS. THE PRINCIPAL INVESTIGATOR, DR. ANDREW COX, COMPLETED HIS MD/PHD AT THE UNIVERSITY OF ROCHESTER, HIS RESIDENCY AND FELLOWSHIP AT CINCINNATI CHILDREN’S HOSPITAL MEDICAL CENTER AND HAS NOW JOINED THE ROCHESTER GENERAL HOSPITAL RESEARCH INSTITUTE WHERE HE WILL LEARN UNDER THE MENTORSHIP OF DR. MICHAEL PICHICHERO. DR. COX’S CAREER GOAL IS TO BECOME A LEADING PEDIATRIC VACCINE CLINICAL TRIALIST CONDUCTING TRANSLATIONAL IMMUNOLOGY WITH INFANT SAMPLES TO DISCOVER NEW PATHWAYS OF ENHANCING VACCINE EFFICACY. DURING THE AWARD PERIOD, HE WILL OBTAIN ADDITIONAL TRAINING THROUGH FORMAL COURSEWORK IN VACCINE IMMUNOLOGY AND BIOINFORMATICS, AND DIRECTED STUDY IN INFANT IMMUNOLOGY AND CLINICAL TRIAL DESIGN, EXECUTION, AND OVERSIGHT. HE WILL PARTICIPATE IN THIS PHASE IIB CLINICAL TRIAL AND IN DOING SO GAIN REAL WORLD EXPERIENCE IN AN INFANT VACCINE CLINICAL TRIAL. HIS PRIMARY MENTOR WILL BE DR. MICHAEL PICHICHERO, DIRECTOR OF THE ROCHESTER GENERAL HOSPITAL RESEARCH INSTITUTE, CO-INVENTOR WITH DRS. INSEL AND ANDERSON OF THE HAEMOPHILUS INFLUENZAE TYPE B PROTEIN CONJUGATED POLYSACCHARIDE VACCINES THAT HAVE SAVED MILLIONS OF INFANT LIVES. OVER THE PAST TWO DECADES, DR. PICHICHERO HAS AMASSED AN INVALUABLE BIORESPOSITORY OF PROSPECTIVELY COLLECTED INFANT SAMPLES THAT WILL PERMIT ANALYSIS OF INFANT VACCINE RESPONSES. DR. COX’S MENTORSHIP TEAM ALSO INCLUDES: (A) DR. RICHARD MALLEY, PROFESSOR OF PEDIATRICS AT HARVARD MEDICAL SCHOOL, CO-INVENTOR THE WHOLE-CELL PNEUMOCOCCAL VACCINE AND EXPERT IN MUCOSAL IMMUNE RESPONSES, (B) DR. RICHARD INSEL, PROFESSOR OF PEDIATRICS AT THE UNIVERSITY OF ROCHESTER, EXPERT IN INFANT VACCINE RESPONSES, (C) DR. STEPHEN WAGGONER, ASSOCIATE PROFESSOR OF PEDIATRICS AT CINCINNATI CHILDREN’S HOSPITAL MEDICAL CENTER, EXPERT IN NATURAL KILLER CELL IMMUNOREGULATION, (D) DR. DAN WEINBERGER, PROFESSOR OF EPIDEMIOLOGY AT THE YALE SCHOOL OF PUBLIC HEALTH, EXPERT IN ADVANCES STATISTICAL METHODS FOR UNDERSTANDING PNEUMOCOCCAL VACCINE RESPONSES, (E) DR. SIMON VAN HAREN, ASSISTANT PROFESSOR OF PEDIATRICS AT HARVARD/BOSTON CHILDREN’S HOSPITAL EXPERT IN IN VITRO ASSAYS OF HUMAN VACCINE RESPONSES AND (F) DR. PORTER ANDERSON, INVENTOR OF MULTIPLE INFANT VACCINES, PIONEER OF PROTEIN CONJUGATE POLYSACCHARIDE VACCINES AND EXPERT IN BACTERIAL PATHOGENESIS.

IMMUNE BIOMARKER DISCOVERY IN CHILDREN SUSCEPTIBLE TO RECURRENT OTITIS MEDIA - PROJECT SUMMARY/ABSTRACT VIRAL-BACTERIAL CO-INFECTIONS ARE OFTEN THE MOST SERIOUS INFECTIOUS EVENTS IN YOUNG CHILDREN, LEADING TO UNPLANNED OFFICE AND HOSPITAL VISITS AS WELL AS SIGNIFICANT MORBIDITY. ACUTE OTITIS MEDIA (AOM) IS A CANONICAL VIRAL-BACTERIAL CO-INFECTION, WHERE AN OPPORTUNISTIC NASOPHARYNGEAL COLONIZER ASCENDS THE EUSTACHIAN TUBE TO INFECT THE MIDDLE EAR DURING A CONCURRENT VIRAL UPPER RESPIRATORY INFECTION. IN A COHORT STUDY OF >1000 CHILDREN OVER THE LAST 14 YEARS, WE HAVE STUDIED AOM PATHOGENESIS, EPIDEMIOLOGY, AND IMMUNITY FROM SIX MONTHS TO FIVE YEARS OF AGE. CHILDREN PRONE TO MULTIPLE AOMS, TERMED STRINGENTLY-DEFINED OTITIS PRONE (SOP) CHILDREN IN OUR COHORT, COMPRISE APPROXIMATELY 10% OF THE TOTAL CHILD POPULATION BUT ACCOUNT FOR THE MAJORITY OF THE HEALTH CARE BURDEN DUE TO AOM AND ARE MORE LIKELY TO UNDERGO SURGERY FOR TYMPANOSTOMY TUBE INSERTION. IT IS CLEAR THAT SOP CHILDREN ARE COLONIZED EARLY IN LIFE WITH ONE OR MORE POTENTIAL OTOPATHOGENS COMPARED TO NON-OTITIS PRONE (NOP) CHILDREN, BUT THIS PREDICTIVE FEATURE OF SUSCEPTIBILITY REQUIRES CONTINUOUS MONITORING THROUGHOUT EARLY LIFE IN ORDER TO DETERMINE. PRELIMINARY DATA SUGGESTS THAT, IN ADDITION TO CHANGES IN NASOPHARYNGEAL (NP) OTOPATHOGEN COLONIZATION AND DEMOGRAPHIC RISK FACTORS, SOP CHILDREN HAVE A PRO-INFLAMMATORY PHENOTYPE IN THE NP AFTER ONE YEAR OF AGE. IMMUNE NETWORK MODELING OF THE NP IMMUNE RESPONSE TO AOM COMPARING SOP AND NOP CHILDREN SUGGESTS AN IL-6, IL-10, IL-17A, AND CCL5 IMMUNE NETWORK MAY BE RESPONSIBLE FOR THE IMMUNE DIFFERENCES OBSERVED IN SOP CHILDREN. FROM THESE DATA, OUR HYPOTHESIS IS THAT EARLY LIFE COLONIZATION WITH OTOPATHOGENS ALTERS NP IMMUNITY, THUS LEAVING SOME CHILDREN SUSCEPTIBLE TO RECURRENT AOM. FURTHER, SOLUBLE NP FACTORS CAN BE IDENTIFIED THAT, WHEN MEASURED IN EARLY LIFE, WILL BE A PREDICTOR OF RECURRENT AOM AND INFORM INDIVIDUALIZED CARE. AIM 1 WILL EMPLOY LC-MS BASED PROTEOMICS IN MATCHED SOP AND NOP SAMPLES TO DETERMINE THE NP PROTEOME AT DEFINED AGES BEFORE, DURING, AND AFTER AOM SUSCEPTIBILITY FOR BIOMARKER IDENTIFICATION. AIM 2 WILL MEASURE THE CANDIDATE BIOMARKERS FROM AIM 1 IN 400 NASAL WASH SAMPLES ACROSS THE CHILD COHORT TO DETERMINE ROBUSTNESS OF THE BIOMARKERS ACROSS CHILD AGE AND COVARIATES. THEREFORE, THIS GRANT PROPOSAL FOCUSES ON THE DETERMINATION OF A BIO-SIGNATURE PREDICTIVE OF SEVERE RECURRENT AOM AND THEREFORE THE NEED FOR TYMPANOSTOMY TUBE INSERTION VERSUS WATCHFUL WAITING THAT WILL BE MEASURED BEFORE OR DURING THE ONSET OF AOM INFECTIONS IN CHILDREN UNDER TWO YEARS OF AGE.

IMMUNOGENICITY OF MORAXELLA CATARRHALIS VACCINE CANDIDATES IN CHILDREN

ANTIBODY & CELLULAR IMMUNE RESPONSES IN CHILDREN AFTER 2 VS 3 DOSES AND PRE VS POST BOOSTER OF PCV13 VACCINE

IMMUNE POTENTIATION TO IMPROVE NEONATAL AND PEDIATRIC VACCINES

SCHOOL-BASED HEALTH CENTERS CAPITAL PROGRAM

BAKER-CEDERBERG ARCHIVAL COLLECTION PRESERVATION