University Of North Carolina AT Chapel Hill

HISPANIC COMMUNITY HEALTH STUDY - STUDY OF LATINOS (HCHS-SOL) COORDINATING CENTER - TASK AREA A - CORE STUDY OPERATIONS

US EPA AT RTP RESEARCH LIBRARY SERVICES

VISN 6 COMMUNITY MAPPING PROGRAM SERVICE

BRIC PHASE 2 UNIVERSITY DIRECT TECHNICAL ASSISTANCE (DTA) NETWORK

THE UNIVERSITY OF ALABAMA RESEARCH TEAM WILL ENSUE THE TRANSFER OF MICE PREVIOUSLY CONSTRUCTED UNDER THIS CONTRACT FROM UNC TO UAB AND WILL BE RESPONSIBLE FOR EXPERIMENTAL DESIGN, IMPLEMENTATION, THE COORDINATION AND IMPLEMENTATION OF THE SCIENTIFIC AGENDA AS OUTLINED INCLUDING 1) ANALYSIS OF HUMAN IMMUNE CELL FUNCTION, 2) EVALUATION OF THE SUITABILITY OF THE NEONATAL TISSUE-DERIVED BLT MODEL FOR THE STUDY OF EBV AND 3) TRAINING FOR THE ENGRAFTMENT AND USE OF THE HIS MOUSE MODEL DEVELOPED UNDER THIS CONTRACT. THE TEAM WILL PROVIDE OVERSIGHT OF THE ENTIRE STUDY, PROVIDE AN ADMINISTRATIVE COMPONENT, IMPLEMENTATION OF ALL PROCEDURES AND PROCESSES AND ASSIST TO PREPARE TECHNICAL REPORTS, PRESENTATIONS AND MEETING AGENDAS.

THE PRIMARY TASKS INCLUDED IN THIS PROJECT, "PHASE 2: UNIVERSITY DIRECT TECHNICAL ASSISTANCE (DTA) NETWORK PROJECT", NC STATE UNIVERSITY (NCSU) WILL USE INFORMATION CAPTURED FROM PHASE 1'S IDENTIFICATION OF INTERESTED UNIVERSITIES AND BEGIN TO RECRUIT THEM TO BE TRAINED BRIC DTA CAPACITY BUILDERS. THIS EFFORT WILL NOT ONLY SUPPORT CURRENT BRIC DTA COMMUNITIES AND TRIBAL NATIONS, IT WILL ALSO HELP FEMA BUILD OUT NATIONAL CAPACITY AND CAPABILITY SUBJECT MATTER EXPERTISE THAT CAN SUPPORT HAZARD MITIGATION ASSISTANCE FOR YEARS TO COME. NCSU WILL BUILD THE FOUNDATIONAL TEAM OF FULL-TIME DEDICATED STAFF TO SUPPORT THE DEVELOPMENT OF THIS PROJECT. THIS FOUNDATIONAL TEAM WILL SUPPORT AND RECRUIT FACULTY, EXTENSION EXPERTS AND NON-TENURED FACULTY TO SERVE IN THE UNIVERSITY NETWORK; MANAGE THE ONGOING DELIVERY OF DTA TRAINING WITHIN THE NETWORK AND SELECTED UNIVERSITIES; ASSESS AND MONITOR THE QUALITY OF THAT TRAINING; AND HELP IMPLEMENT THE UNIVERSITY FRAMEWORK DEVELOPED IN PHASE 1.

THE RESEARCH TEAM WILL PERFORM SITE ADMINISTRATION FOR WORK PERFORMED AT MCLEAN HOSPITAL AND LEAD THE NEUROIMAGING COMPONENTS OF THE PROJECT; OVERSEE CURATION AND ANALYSES OF THE NEUROCOGNITIVE END OF THE PROPOSAL AND WORK COOPERATIVELY TO PERFORM ADVANCED COMPUTATIONAL MODELING OF NEUROCOGNITIVE AND PSYCHIATRIC SYMPTOM DATA IN CONJUNCTION WITH OTHER PERFORMANCE SITES. THE TEAM WILL ALSO OVERSEE AND DIRECT ANALYSES OF THE PSYCHOPHYSIOLOGICAL COMPONENT OF THE PROPOSAL.

THE UNIVERSITY OF MINNESOTA (UM) RESEARCHERS WILL BE THE CENTRAL LABORATORY FOR THE STUDY TITLED "HISPANIC COMMUNITY HEALTH STUDY-STUDY OF LATINOS (HCHS-SOL) COORDINATION CENTER". UM WILL COMPLETE THE FOLLOWING TASKS: A5. ESTABLISH AND MANAGE THE BIOLOGICAL SPECIMEN REPOSITORY; A5A. MAINTAIN THE HCHS/SOL BIOLOGIC SPECIMEN REPOSITORY IN ACCORDANCE WITH HCHS/SOL POLICIES AND PROCEDURES; A5B. INCORPORATE SURPLUS SPECIMENS FROM ANCILLARY STUDIES; A5C. TRACK SAMPLES; A5D. PROVIDE SPECIMENS TO APPROVED INVESTIGATORS IN ACCORDANCE WITH STUDY POLICIES AND PROCEDURES; A5E. CONDUCT QUALITY MANAGEMENT PROCEDURES; B2.3. PLAN AND CONDUCT THE RECEIPT AND PROCESSING OF COLLECTED BLOOD AND URINE SAMPLES; B2.5. TRAINING OF RELEVANT STAFF AT ALL FIELD CENTERS; C.3. PROVIDE SMOOTH TRANSFER OF ALL BIOLOGICAL SAMPLES; C.4. PREPARE AN APPLICATION FOR TRANSFER OF BIOLOGICAL SPECIMENS TO THE NHLBI BIOSPECIMEN REPOSITORY; C.5. SHIP ALL BIOLOGICAL SAMPLES TO THE NHLBI BIOSPECIMEN REPOSITORY AND/OR OTHER BIOREPOSITORIES.

WAYNE STATE UNIVERSITY RESEARCH TEAM WILL ASSIST WITH PSYCHOPHYSIOLOGICAL DATA PROCESSING, DATA QUALITY AND ANALYSIS INCLUDING ELECTROMYOGRAM (EMG), SKIN CONDUCTANCE/ELECTRODERMAL ACTIVITY (SC EDA) AND HEART RATE AND HEART-RATE VARIABILITY (HR/HRV) DATA USING EXISTING DATA FROM ALL STUDY SITES.

DEVELOPMENT OF A NOVEL 2-PYRIMIDONE (SRI-42718) AS A POTENT INHIBITOR OF CHIKUNGYA VIRUS INFECTION AND DISEASE

OPTION 9B: 0258-A730-4609 RECOVERY AND IMMUNOLOGIC COMPARISONS ACROSS THE GROUP B MERBECOVIRUSES USING ANTIGENIC CARTOGRAPHY INTRODUCTION: MERBECOVIRUSES INCLUDE A DIVERSE ARRAY OF POSITIVE STRANDED RNA VIRUSES WITHIN THE BETACORONAVIRUS GENUS AND INCLUDE THE HIGHLY PATHOGENIC MERS-COV STRAIN THAT CAUSED 2604 LABORATORY-CONFIRMED CASES OF MIDDLE EAST RESPIRATORY SYNDROME (MERS) INCLUDING 936 ASSOCIATED DEATHS AT A CASE-FATALITY RATIO (CFR) OF 36% SINCE 2012. IMPORTANTLY, NUMEROUS ZOONOTIC BAT MERS-LIKE VIRUSES CIRCULATE IN NATURE INCLUDING SEVERAL STRAINS THAT CAN USE THE HUMAN DIPEPTIDYL PEPTIDASE RECEPTOR (HDPP4) FOR DOCKING AND ENTRY. SOME REPLICATE EFFICIENTLY OR ARE ANTICIPATED TO REPLICATE EFFICIENTLY IN PRIMARY HUMAN AIRWAY EPITHELIAL CELLS (E.G., MERS-422, MJHKU4R -COV-1, NEO, ), WHILE MOST HAVE NOT BEEN STUDIED. CURRENTLY, THERE ARE NO APPROVED VACCINES OR THERAPEUTICS FOR USE AGAINST MERS-COV INFECTION OR ANY OTHER MERBECOVIRUS. GIVEN THE EXTREME PATHOGENIC POTENTIAL OF MERS-COV, COUPLED WITH THE PRESENCE OF MERBECOVIRUSES THAT CAN USE DPP4 OR ANGIOTENSIN 1 CONVERTING ENZYME 2 (ACE2) AS RECEPTORS FOR DOCKING AND ENTRY, THE DEVELOPMENT OF PANMERBECOVIRUS VACCINES IS STILL CONSIDERED HIGH PRIORITY TARGETS FOR COUNTERMEASURE INVESTMENTS BY HEALTH AGENCIES ACROSS THE WORLD (HTTPS://WWW.WHO.INT/TEAMS/BLUEPRINT). THE OVERARCHING GOAL OF THIS PROPOSAL IS TO DETERMINE THE ANTIGENIC DISTANCE BETWEEN HIGHLY HETEROGENEOUS MERBECOVIRUSES, CREATE AN ANTIGENIC CARTOGRAPHY MAP, AND PRODUCE DEFINED SERA AND RECOMBINANT VIRUS REAGENTS THAT WILL ENHANCE GLOBAL PREPAREDNESS AGAINST FUTURE MERBECOVIRUS EPIDEMICS AND PANDEMICS. THE PROPOSAL HAS THREE AIMS: AIM I) PRODUCTION AND CHARACTERIZATION OF MERBECOVIRUS SPIKE ANTIGENS AND PRODUCTION OF MURINE ANTISERUM. FROM PUBLISHED SEQUENCES, MERBECOVRIRUS SPIKE GENES WILL BE SYNTHESIZED AND EXPRESSED AT UNC€„¢S PROTEOMIC CORE. RECOMBINANT PROTEINS PLUS ADJUVANT WILL BE INJECTED INTO RODENTS FOR THE PRODUCTION OF SERUM NEUTRALIZING ANTIBODIES. AIM II) RECOVERY OF RECOMBINANT MERBECOVIRUSES AND DERIVATIVE VIRUSES ENCODING NANOLUCIFERASE. (FOR LIVE VIRUS NEUTRALIZATION ASSAY DEVELOPMENT). A SELECT PANEL OF RECOMBINANT MERBECOVIRUSES WILL BE ISOLATED FROM PUBLISHED SEQUENCES, INCLUDING DERIVATIVES THAT ENCODE THE NANOLUCIFERASE GENE IN REPLACE OF A KNOWN ACCESSORY ORF. LIVE VIRUS NEUTRALIZATION ASSAYS WILL BE DEVELOPED USING A 96 WELL FORMAT AS PREVIOUSLY DESCRIBED BY OUR GROUP. AIM III) PERFORM LIVE VIRUS CROSS NEUTRALIZATION ASSAYS AND ANTIGENIC CARTOGRAPHY. USING CELLS EXPRESSING HDPP4, WE WILL PERFORM LIVE VIRUS NLUC NEUTRALIZATION ASSAYS ACROSS EACH MEMBER OF THE PANEL, USING MURINE ANTISERUM (N=3/EACH SPIKE). THE RESULTS WILL BE SHARED WITH DR. DEREK SMITH, WHO WILL PERFORM ANTIGENIC CARTOGRAPHY STUDIES ON THE DATA. DELIVERABLES: RECOMBINANT MERBECOVIRUS SPIKES, RECOMBINANT WILDTYPE AND DERIVATIVE VIRUSES ENCODING NLUC, REFERENCE SERA, ANTIGENIC CARTOGRAPHY MAPS, IDENTIFICATION OF BNAB FROM EXISTING PANELS OBTAINED FROM COLLABORATORS ACROSS THE US AND ELSEWHERE. OPTION 20B: IF300302087 RECOVERY AND IMMUNOLOGIC COMPARISONS ACROSS THE GROUP B MERBECOVIRUSES USING ANTIGENIC CARTOGRAPHY

THE OVERALL GOAL OF THIS PROJECT IS TO EVALUATE VARIOUS ADJUVANTS AND COMBINATIONS OF THESE ADJUVANTS FOR USE IN MUCOSAL IMMUNOTHERAPY FOR PEANUT ALLERGY. DR. KULIS AND HIS TEAM AT UNC CHAPEL HILL WILL PERFORM IN VIVO MOUSE STUDIES, ASSAY HUMAN PERIPHERAL BLOOD CELLS, AND QUANTIFY IMMUNOLOGIC RESPONSES TO ADJUVANTS AND PEANUT FROM BOTH MOUSE AND HUMAN BLOOD. SPECIFICALLY, WE WILL EVALUATE SIX ADJUVANT FORMULATIONS IN CELL CULTURE ASSAYS WITH HUMAN T AND B CELLS FROM BLOOD, PRIMARILY INVESTIGATING CYTOKINE RESPONSES AND THEN SENDING CELLS FROM THESE EXPERIMENTS TO DUKE FOR OMICS EXPERIMENTS. FOR THE MOUSE STUDIES, WE WILL EVALUATE THE SAME SIX ADJUVANTS PLUS PEANUT BY ADDING THE ADJUVANTS TO SPLEEN AND LYMPH NODE CELLS IN CULTURE. WE WILL ALSO ADMINISTER THE ADJUVANTS AND PEANUT BY THE SUBLINGUAL ROUTE TO LIVE MICE THAT ARE EITHER NOT SENSITIZED TO PEANUT OR IN MICE THAT HAVE AN ESTABLISHED PEANUT ALLERGY. WE WILL PERFORM THESE EXPERIMENTS AT UNC, AND ALSO SAVE VARIOUS SAMPLES (SPLEEN, LYMPH NODE, SERUM, SALIVA, AND FECAL PELLETS) TO SHIP TO DUKE FOR OMICS STUDIES. ULTIMATELY, THE SIX ADJUVANTS WILL BE EVALUATED FOR THEIR SAFETY AND EFFICACY IN THE PEANUT ALLERGIC MICE. SINCE THIS PROJECT INVOLVES TEAM MEMBERS AT DUKE AND INIMMUNE, WE WILL ALSO PARTICIPATE IN BIWEEKLY MEETINGS TO DISCUSS EXPERIMENTAL DESIGN, PROGRESS, AND DATA ANALYSIS. TWO TEAM MEMBERS FROM UNC (DR. KULIS AND DR. SMEEKENS) WILL ATTEND ANNUAL MEETINGS AT NIH IN BETHESDA, MD. WE ANTICIPATE PUBLISHING SEVERAL MANUSCRIPTS BASED ON THE WORK DONE AT UNC IN COLLABORATION WITH DUKE AND INIMMUNE, WHICH THE UNC TEAM WILL BE HEAVILY INVOLVED IN WRITING.

SUBCONTRACT 2-312-0217290 MOD 8

UNIVERSITY OF NORTH CAROLINA