12873SUBS
OPTION 4 ACTIVITIES: CONDUCT TWO PHASE 1 CLINICAL TRIALS IN THE CONTROLLED HUMAN MYCOBACTERIAL CHALLENGE MODEL USING AN ESTABLISHED MODEL OF AEROSOLIZED BCG DELIVERED TO THE LUNGS OF HUMANS, FOLLOWED BY BRONCHOSCOPIC ASSESSMENT OF MUCOSAL IMMUNITY, ASSESS VACCINE-MEDIATED PROTECTION FROM THIS CHALLENGE. TO DATE WE HAVE DELIVERED BCG VIA THE AEROSOL ROUTE TO OVER 65 VOLUNTEERS AND REPEATED THE DOSE ESCALATION FROM 1X104CFU - 1 X 107CFU BCG WITH NO SAFETY CONCERNS. PROTOCOL SUMMARY OF THE TWO PHASE I CLINICAL TRIALS: TB0441: A CLINICAL CHALLENGE STUDY TO EVALUATE CONTROLLED HUMAN INFECTION WITH BCG ADMINISTERED BY THE AEROSOL INHALED ROUTE IN HISTORICALLY BCG-VACCINATED HEALTHY ADULT VOLUNTEERS TB0451: A PHASE I CLINICAL TRIAL TO EVALUATE (I) THE ADAPTIVE IMMUNE RESPONSE TO A CONTROLLED HUMAN INFECTION WITH AEROSOL BCG; AND (II) THE PROTECTIVE EFFICACY OF A PRIOR BCG VACCINATION AND/OR ID93+GLA-SE VACCINATION USING THIS MODEL
University Of Oxford
Definitive Contract 75N93021C00029
$1.2m 1/31/25 13494SUBS
THROUGH THE EXECUTION OF THIS CONTRACT, WE WILL EXAMINE BASIC INDUCTION OF INNATE AND ADAPTIVE IMMUNITY FROM VACCINATION, INCLUDING STUDIES THAT ADDRESS NONTUBERCULOUS MYCOBACTERIA (NTM) INTERFERENCE, RNA DELIVERY, PRIME-BOOST REGIMENS (INCLUDING BCG PRE-EXPOSURE), TRANSCRIPTOMIC HOST SIGNATURES, PROTEOMICS, SYSTEMS BIOLOGY AND DURABLE IMMUNE MEMORY FOR THE FURTHER ADVANCEMENT OF THE EFFORT TO DESIGN AND EVALUATE AN EFFICACIOUS VACCINE AGAINST MYCOBACTERIUM TUBERCULOSIS (M.TB). THE WORK UNDER THIS CONTRACT MAY INCLUDE THE POSSIBLE DISTRIBUTION OF DE-IDENTIFIED HUMAN SUBJECT PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC), SERUM, AND OTHER CLINICAL SAMPLES TO SCRI AND THE PHOENIX PARTNERS. NHP SAMPLES AND/OR DOWNSTREAM DATA MAY BE SHARED WITH THE PARTNERS ON THIS CONTRACT. OPTION 3 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN THE NHP MODEL OF TB TASK 3.1: NHP SAFETY AND EFFICACY AGAINST ULTRA-LOW DOSE AEROSOL (ULDA) M.TB ERDMAN TO ENSURE THAT BIOLOGICAL RESULTS GENERATED IN THE VARIOUS CONSORTIUM LABS ARE COMPARABLE, WE WILL STANDARDIZE THE PRIMARY ASSAYS USED IN IMMUNOGENICITY ASSESSMENTS FOR EACH SPECIES. IN LINE WITH THE PROJECT GOALS TO DEVELOP A CROSS-SPECIES INTERROGATION PLATFORM, WE WILL HARMONIZE KEY ASSAYS ACROSS MULTIPLE SPECIES. SCRI WILL APPOINT AN OVERALL TASK LEADER TO COORDINATE AND OVERSEE THE WORK. ALL ASSAY STANDARD OPERATING PROCEDURES (SOP) WILL BE SHARED WITH A PRECLINICAL LABORATORY LEAD, DESIGNATED FOR EACH ASSAY, WHO WILL BE RESPONSIBLE FOR HARMONIZING. FINAL SOPS WILL BE SHARED AND LEAD ASSAY LABS WILL CONDUCT SIDE-BY-SIDE TRAINING SESSIONS, AS WELL AS, MAINTAIN AND DISTRIBUTE COMMON REFERENCE STANDARDS AND REAGENTS, SUCH AS IDENTICAL STIMULATION ANTIGENS (BCG, PPD, SEB, PEPTIDE POOLS AS DESCRIBED BELOW (NTM MEGAPOOL, MTB300, MTB300-ID93, AND MTB300-M72), 15-MER PEPTIDES FOR ID93, COMPONENTS OF ID93, AND M72,AND UNSTIMULATED) AND BCG VACCINATION STRAIN (BCG AJ/BCG SSI). THESE REGENTS WILL BE INCLUDED IN AN OPTIMIZED MULTICOLOR IMMUNOFLUORESCENCE PANEL (OMIP). FURTHERMORE, SSI WILL ASSIST IN THE ANALYSIS OF REACTIVITY OF PEPTIDES IN HUMAN AND ANIMAL MODELS IN ANTIGENICITY ASSAYS PRIOR TO IMPLEMENTATION IN OPTIONS 1-4. A POOL OF 15-MER T CELL EPITOPES WHICH ARE FOUND IN DIVERSE NTMS BUT ABSENT FROM M.TB (PMID: 25548174) WILL BE SUPPLIED BY SSI IN THE OPTION 3 PERIOD TO COLLABORATOR LABS THAT REQUIRE THEM FOR IMMUNE PHENOTYPING ASSAYS. TAKING ADVANTAGE OF THE RECENTLY DEVELOPED APPROACH OF COMBINING A LARGE NUMBER OF EPITOPES IN ONE SINGLE POOL AS A "MEGAPOOL" (PMID: 27409590) WE COMBINE ALL EPITOPES IDENTIFIED IN THE PNAS STUDY TOGETHER WITH PEPTIDES IDENTIFIED BY OTHER MEMBERS OF OUR GROUP (PMID: 22046285). IN SUMMARY, LJI AND/OR SSI WILL PROVIDE: A. MEGAPOOL OF 15-MER T CELL EPITOPES WHICH ARE FOUND IN DIVERSE NTMS BUT ABSENT FROM M.TB B. MEGAPOOL OF M.TB -DERIVED EPITOPES (MTB300). C. MEGAPOOL OF M.TB -DERIVED EPITOPES FROM WHICH ID93-DERIVED EPITOPES WERE OMITTED (MTB300-ID93). D. MEGAPOOL OF M.TB-DERIVED EPITOPES FROM WHICH M72-DERIVED EPITOPES WERE OMITTED (MTB300-M72) A SUMMARY REPORT OF ALL ACTIVITIES AND STANDARDIZED PROTOCOLS FROM THE OPTION 3 PERIOD WILL BE DRAFTED AND SUBMITTED TO NIAID FOR REVIEW AND APPROVAL. SSI WILL PROVIDE ALL THE NECESSARY DATA AND INPUT REQUIRED FOR THE COMPLETION AND ACCEPTANCE OF THE ANIMAL STUDY REPORT. SHIPMENT PLANNING AND DOCUMENTATION WILL BE PROVIDED FOR THE PEPTIDE POOLS TO BE USED IN PRECLINICAL (OPTION 3) NHP IMMUNOLOGIC STUDIES. OPTION 4 ACTIVITIES: CONDUCT PHASE 1 CLINICAL TRIAL IN THE CONTROLLED HUMAN MYCOBACTERIAL CHALLENGE MODEL TASK 4.3 CLINICAL FOLLOW-UP PHASE TO ENSURE THAT BIOLOGICAL RESULTS GENERATED IN THE VARIOUS CONSORTIUM LABS ARE COMPARABLE, WE WILL STANDARDIZE THE PRIMARY ASSAYS USED IN IMMUNOGENICITY ASSESSMENTS FOR EACH SPECIES. IN LINE WITH THE PROJECT GOALS TO DEVELOP A CROSS-SPECIES INTERROGATION PLATFORM, WE WILL HARMONIZE KEY ASSAYS ACROSS MULTIPLE SPECIES. SCRI WILL APPOINT AN
Statens Serum Institut
Definitive Contract 75N93021C00029
$67.4k 1/31/25 13473SUBS
THIS STATEMENT OF WORK (SOW) OUTLINES THE ACTIVITIES THAT THE SITES Â DENVER RESEARCH INSTITUTE (AKA DRI, ADMINISTRATIVE/SUBCONTRACT SITE) AND ROCKY MOUNTAIN REGIONAL VA MEDICAL CENTER (AKA RMR-VAMC, EXPERIMENTAL WORK SITE) Â WILL BE PERFORMING FOR THIS PROJECT. NOTE THAT THE TASK NUMBERS BELOW REFLECT THE NUMBERING OF THE OVERALL ACTIVITIES IN THE PRIME CONTRACT. THROUGH THE EXECUTION OF THIS CONTRACT, WE WILL EXAMINE BASIC INDUCTION OF INNATE AND ADAPTIVE IMMUNITY FROM VACCINATION, INCLUDING STUDIES THAT ADDRESS NONTUBERCULOUS MYCOBACTERIA (NTM) INTERFERENCE, RNA DELIVERY, PRIME-BOOST REGIMENS (INCLUDING BCG PRE-EXPOSURE), TRANSCRIPTOMIC HOST SIGNATURES, SYSTEMS BIOLOGY, AND DURABLE IMMUNE MEMORY FOR THE FURTHER ADVANCEMENT OF THE EFFORT TO DESIGN AND EVALUATE AN EFFICACIOUS VACCINE AGAINST MYCOBACTERIUM TUBERCULOSIS (M.TB). THE WORK UNDER THIS CONTRACT MAY INCLUDE THE POSSIBLE DISTRIBUTION OF DE-IDENTIFIED HUMAN SUBJECT PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC), SERUM, AND OTHER CLINICAL SAMPLES TO SCRI AND THE PHOENIX PARTNERS. NHP SAMPLES AND/OR DOWNSTREAM DATA MAY BE SHARED WITH THE PARTNERS ON THIS CONTRACT. OPTION 1 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN MOUSE TB MODELS TASK 1.4: EVALUATE POD EFFICACY WITH NTM (HN878 P1) TO ENSURE THAT BIOLOGICAL RESULTS GENERATED IN THE VARIOUS CONSORTIUM LABS ARE COMPARABLE, WE WILL STANDARDIZE THE PRIMARY ASSAYS USED IN IMMUNOGENICITY ASSESSMENTS FOR EACH SPECIES. IN LINE WITH THE PROJECT GOALS TO DEVELOP A CROSS-SPECIES INTERROGATION PLATFORM, WE WILL HARMONIZE KEY ASSAYS ACROSS MULTIPLE SPECIES. SCRI WILL APPOINT AN OVERALL TASK LEADER TO COORDINATE AND OVERSEE THE WORK. ALL ASSAY STANDARD OPERATING PROCEDURES (SOP) WILL BE SHARED WITH A PRECLINICAL LABORATORY LEAD, DESIGNATED FOR EACH ASSAY, WHO WILL BE RESPONSIBLE FOR HARMONIZING. FINAL SOPS WILL BE SHARED AND LEAD ASSAY LABS WILL CONDUCT SIDE-BY-SIDE TRAINING SESSIONS, AS WELL AS MAINTAIN AND DISTRIBUTE COMMON REFERENCE STANDARDS AND REAGENTS, SUCH AS IDENTICAL STIMULATION ANTIGENS (BCG, PPD, SEB, PEPTIDE POOLS, MYCOBACTERIAL LYSATES AND BCG VACCINATION STRAIN (BCG AJ/BCG SSI). THESE REAGENTS WILL BE INCLUDED IN AN OPTIMIZED MULTICOLOR IMMUNOFLUORESCENCE PANEL (OMIP). RMR-VAMC WILL USE THEIR EXPANSIVE STOCKS OF NTM ISOLATES TO GENERATE BATCHES OF A VARIETY OF APPROXIMATELY 5-10 NTM LIVE CULTURES, LYSATES AND CULTURE FILTRATES DURING OPTION 1. THESE REAGENTS WILL BE DISTRIBUTED TO COLLABORATOR SITES TO BE USED IN CROSS-SPECIES AND CROSS-SITE ASSAY VALIDATION AND STANDARDIZATION AS NEEDED. THESE REAGENTS WILL FURTHER BE USED TO EXECUTE ASSAYS EVALUATING THE EFFECTS OF NTM PRE-EXPOSURE IN MOUSE, GUINEA PIG, NONHUMAN PRIMATE (NHP) AND HUMAN SAMPLES, INCLUDING EVALUATING NTM-SPECIFIC ANTIBODY RESPONSES IN OPTIONS 1-4. A SUMMARY REPORT OF ALL ACTIVITIES AND RESULTS FROM OPTION 1 WILL BE DRAFTED AND SUBMITTED TO NIAID FOR REVIEW AND APPROVAL. RMR-VAMC WILL PROVIDE ALL THE NECESSARY DATA AND INPUT REQUIRED FOR THE COMPLETION AND ACCEPTANCE OF THE FINAL REPORT FOR OPTION 1 ACTIVITIES. CONTRACT PERIOD-SPECIFIC TASK TABLE OF DELIVERABLES: DELIVERABLE TASK DESCRIPTION PERIOD OF PERFORMANCE DUE DATE DUE THIS CONTRACT PERIOD 1.4 EVALUATE POD EFFICACY WITH NTM (HN878 P1) 8/1/2024 Â 7/31/2025 7/31/2025 OPTION 3 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN THE NHP MODEL OF TB TASK 3.4: EX VIVO NHP MACROPHAGE STUDY TASK 3.4: ANALYZE THE EFFECTS THE DIFFERENT VACCINE STRATEGIES HAVE ON NONHUMAN PRIMATE (NHP) MACROPHAGE CONTROL OF AN EX VIVO M.TB INFECTION. IN EX VIVO EXPERIMENTS, RMR-VAMC WILL DETERMINE WHAT EFFECTS THE DIFFERENT VACCINATION STRATEGIES IN NHP HAVE ON THE ABILITY OF THEIR MACROPHAGES TO CONTROL AN EX VIVO INFECTION AND ON MACROPHAGE EFFECTOR FUNCTIONS. IN GROUPS OF NHP WITH DIFFERENT VACCINE STRATEGIES, PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) WILL BE OBTAINED POST-BOOST AND SENT PRE-CHALLENGE AT 5 X 1
Denver Research Institute
Definitive Contract 75N93021C00029
$136.4k 11/30/24 13476SUBS
THIS STATEMENT OF WORK (SOW) OUTLINES THE ACTIVITIES THAT FRED HUTCHINSON CANCER CENTER (FHCC) WILL BE PERFORMING. NOTE THAT THE TASK NUMBERS BELOW REFLECT THE NUMBERING OF THE OVERALL ACTIVITIES IN THE PRIME CONTRACT. ALTHOUGH THIS SOW DETAILS THE COMPLETE SUITE OF PROPOSED WORK, THE TASKS ASSOCIATED WITH THIS CONTRACT ITERATION ARE LIMITED TO THE SPECIFIC ACTIVITIES OUTLINED BELOW, DELIVERABLES FOR THIS CONTRACT PERIOD ARE HIGHLIGHTED. THROUGH THE EXECUTION OF THIS CONTRACT, WE WILL EXAMINE BASIC INDUCTION OF INNATE AND ADAPTIVE IMMUNITY FROM VACCINATION, INCLUDING STUDIES THAT ADDRESS NONTUBERCULOUS MYCOBACTERIA (NTM) INTERFERENCE, RNA VACCINE DELIVERY, PRIME-BOOST REGIMENS (INCLUDING BCG PRE-EXPOSURE), TRANSCRIPTOMIC HOST SIGNATURES, SYSTEMS BIOLOGY AND DURABLE IMMUNE MEMORY FOR THE FURTHER ADVANCEMENT OF THE EFFORT TO DESIGN AND EVALUATE AN EFFICACIOUS VACCINE AGAINST MYCOBACTERIUM TUBERCULOSIS (M.TB) THE WORK UNDER THIS CONTRACT MAY INCLUDE THE POSSIBLE DISTRIBUTION OF DE-IDENTIFIED HUMAN SUBJECT PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC), SERUM, AND OTHER CLINICAL SAMPLES TO SCRI AND THE PHOENIX PARTNERS. NHP SAMPLES AND/OR DOWNSTREAM DATA MAY BE SHARED WITH THE PARTNERS ON THIS CONTRACT. OPTION 3 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN THE NHP MODEL OF TB TASK 3.5 TRANSCRIPTOMIC ANALYSIS OF NHP SAMPLES. FHCC WILL EXECUTE GENE EXPRESSION PROFILING WITH RNASEQ/NANOSTRING ASSAYS ON NHP SAMPLES GENERATED IN OPTION 3 AT UKHSA. TRANSCRIPTOMIC ANALYSIS WILL BE FOCUSED ON IDENTIFYING A PERIPHERAL BLOOD SURROGATE ENDPOINT FOR THE M.TB ERDMAN ULDA CHALLENGE OUTCOMES. THE INITIAL UNBIASED RNA SEQUENCING APPROACH WILL USE WHOLE-BLOOD SAMPLES FROM PRE- AND POST-CHALLENGE TIME POINTS. SPECIFICALLY, WE WILL LOOK FOR TRANSCRIPTS THAT ARE CORRELATED WITH M.TB COLONY FORMING UNITS (CFU) AND M.TB QPCR ASSAYS FROM BRONCHOALVEOLAR LAVAGE (BAL), THE PRIMARY CHALLENGE OUTCOMES. IN ADDITION TO ABSOLUTE ABUNDANCE AT POST-CHALLENGE TIME POINTS, WE WILL ALSO LOOK FOR CHANGES IN TRANSCRIPT ABUNDANCE RELATIVE TO THE DAY OF CHALLENGE AS A POTENTIAL CORRELATE OF CHALLENGE OUTCOME. AS WE BUILD A MODEL TO PREDICT CHALLENGE OUTCOME FROM THESE GENE EXPRESSION MEASURES WE WILL SPECIFICALLY CONSIDER TRANSCRIPTS THAT HAVE PREVIOUSLY BEEN IDENTIFIED AS PREDICTORS OF PROGRESSION TO TB DISEASE, SUCH AS TYPE I IFN-RELATED GENES WHOSE EXPRESSION INCREASES DURING DISEASE PROGRESSION. THE HUMAN EXPRESSION SIGNATURES WILL BE EVALUATED IN NHPS AND VICE VERSA; ADDITIONALLY, A JOINT MODEL WILL BE DEVELOPED, ALLOWING FOR DIFFERENCES IN NHP AND HUMAN ASSOCIATIONS, WHILE IDENTIFYING A COMMON GENE SIGNATURE. ONCE TRANSCRIPTS OR GENES HAVE BEEN IDENTIFIED, A TARGETED CROSS-SPECIES NANOSTRING PANEL WILL BE DEVELOPED FOR EVALUATION IN THE SMALL ANIMAL MODELS AS WELL AS IN FUTURE NHP AND CLINICAL TRIALS. WE PLAN TO DEVELOP A NANOSTRING NCOUNTER GENE PANEL WHICH CAN ACCOMMODATE UP TO 800 GENES AND WOULD BE SIGNIFICANTLY MORE COST EFFECTIVE THAN RNA SEQUENCING. ALTERNATIVELY, DEPENDING ON THE COMPLEXITY OF THE GENE PANEL, IT COULD BE DEVELOPED AS A 96 TRANSCRIPT/GENE (INCLUDING HOUSEKEEPING GENES) QPCR BIOMARK FLUIDIGM ASSAY. TASK 3.7 COMPARE IMMUNE PROFILES IN NHP, SMALL ANIMAL MODELS AND HUMANS TO IDENTIFY CORRELATES OF PROTECTION. SUBTASK 3.7.4 INTEGRATED ANALYSIS AND DYNAMICAL SYSTEMS MODELING OF EXPERIMENTAL IMMUNOLOGY DATA ACROSS ALL SPECIES EXPERIMENTAL DATA WILL BE TRANSFERRED TO THE STATISTICAL CENTER AND A FORMAL INTER-SITE AND INTER-SPECIES VARIABILITY ASSESSMENT WILL BE PERFORMED. VARIABILITY WILL BE DETERMINED USING COEFFICIENTS OF VARIATION (CV), MEAN AND STANDARD DEVIATION OF RESPONSES. DESIRED CUT-OFFS FOR ACCEPTABLE CVS WILL BE PRE-SPECIFIED FOR EACH ASSAY. EFFORT IN THE BASE PERIOD WILL HAVE BEEN MADE TO STANDARDIZE THE ASSAYS AND HARMONIZATION ASSESSMENTS WILL HAVE BEEN REPEATED IF CVS DID NOT MEET THE CUT OFF. IMMUNOGENICITY AND SYSTEMS BIOLOGY: INNATE AND ADAPTIVE IMMUNITY, INCLUDING EX-V
Fred Hutchinson Cancer Center
Definitive Contract 75N93021C00029
$237.1k 11/30/24 13477SUBS
THIS STATEMENT OF WORK (SOW) OUTLINES THE ACTIVITIES THAT THE SITES Â DENVER RESEARCH INSTITUTE (AKA DRI, ADMINISTRATIVE/SUBCONTRACT SITE) AND ROCKY MOUNTAIN REGIONAL VA MEDICAL CENTER (AKA RMR-VAMC, EXPERIMENTAL WORK SITE) Â WILL BE PERFORMING FOR THIS PROJECT. NOTE THAT THE TASK NUMBERS BELOW REFLECT THE NUMBERING OF THE OVERALL ACTIVITIES IN THE PRIME CONTRACT. THROUGH THE EXECUTION OF THIS CONTRACT, WE WILL EXAMINE BASIC INDUCTION OF INNATE AND ADAPTIVE IMMUNITY FROM VACCINATION, INCLUDING STUDIES THAT ADDRESS NONTUBERCULOUS MYCOBACTERIA (NTM) INTERFERENCE, RNA DELIVERY, PRIME-BOOST REGIMENS (INCLUDING BCG PRE-EXPOSURE), TRANSCRIPTOMIC HOST SIGNATURES, SYSTEMS BIOLOGY, AND DURABLE IMMUNE MEMORY FOR THE FURTHER ADVANCEMENT OF THE EFFORT TO DESIGN AND EVALUATE AN EFFICACIOUS VACCINE AGAINST MYCOBACTERIUM TUBERCULOSIS (M.TB). THE WORK UNDER THIS CONTRACT MAY INCLUDE THE POSSIBLE DISTRIBUTION OF DE-IDENTIFIED HUMAN SUBJECT PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC), SERUM, AND OTHER CLINICAL SAMPLES TO SCRI AND THE PHOENIX PARTNERS. NHP SAMPLES AND/OR DOWNSTREAM DATA MAY BE SHARED WITH THE PARTNERS ON THIS CONTRACT. OPTION 1 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN MOUSE TB MODELS TASK 1.4: EVALUATE PREVENTION OF DISEASE (POD) EFFICACY WITH NTM (M.TB HN878 P1) TO ENSURE THAT BIOLOGICAL RESULTS GENERATED IN THE VARIOUS CONSORTIUM LABS ARE COMPARABLE, WE WILL STANDARDIZE THE PRIMARY ASSAYS USED IN IMMUNOGENICITY ASSESSMENTS FOR EACH SPECIES. IN LINE WITH THE PROJECT GOALS TO DEVELOP A CROSS-SPECIES INTERROGATION PLATFORM, WE WILL HARMONIZE KEY ASSAYS ACROSS MULTIPLE SPECIES. SCRI WILL APPOINT AN OVERALL TASK LEADER TO COORDINATE AND OVERSEE THE WORK. ALL ASSAY STANDARD OPERATING PROCEDURES (SOP) WILL BE SHARED WITH A PRECLINICAL LABORATORY LEAD, DESIGNATED FOR EACH ASSAY, WHO WILL BE RESPONSIBLE FOR HARMONIZING. FINAL SOPS WILL BE SHARED AND LEAD ASSAY LABS WILL CONDUCT SIDE-BY-SIDE TRAINING SESSIONS, AS WELL AS MAINTAIN AND DISTRIBUTE COMMON REFERENCE STANDARDS AND REAGENTS, SUCH AS IDENTICAL STIMULATION ANTIGENS (BCG, PPD, SEB, PEPTIDE POOLS, MYCOBACTERIAL LYSATES AND BCG VACCINATION STRAIN (BCG AJ/BCG SSI). THESE REAGENTS WILL BE INCLUDED IN AN OPTIMIZED MULTICOLOR IMMUNOFLUORESCENCE PANEL (OMIP). RMR-VAMC WILL USE THEIR EXPANSIVE STOCKS OF NTM ISOLATES TO GENERATE BATCHES OF A VARIETY OF APPROXIMATELY 5-10 NTM LIVE CULTURES, LYSATES AND CULTURE FILTRATES DURING OPTION 1. THESE REAGENTS WILL BE DISTRIBUTED TO COLLABORATOR SITES TO BE USED IN CROSS-SPECIES AND CROSS-SITE ASSAY VALIDATION AND STANDARDIZATION AS NEEDED. THESE REAGENTS WILL FURTHER BE USED TO EXECUTE ASSAYS EVALUATING THE EFFECTS OF NTM PRE-EXPOSURE IN MOUSE, GUINEA PIG, NONHUMAN PRIMATE (NHP) AND HUMAN SAMPLES, INCLUDING EVALUATING NTM-SPECIFIC ANTIBODY RESPONSES IN OPTIONS 1-4. A SUMMARY REPORT OF ALL ACTIVITIES AND RESULTS FROM OPTION 1 WILL BE DRAFTED AND SUBMITTED TO NIAID FOR REVIEW AND APPROVAL. DRI/RMR-VAMC WILL PROVIDE ALL THE NECESSARY DATA AND INPUT REQUIRED FOR THE COMPLETION AND ACCEPTANCE OF THE FINAL REPORT FOR OPTION 1 ACTIVITIES. CONTRACT PERIOD-SPECIFIC TASK TABLE OF DELIVERABLES: DELIVERABLES TASK DESCRIPTION PERIOD OF PERFORMANCE DUE DATE DUE THIS CONTRACT PERIOD 1.4 EVALUATE POD EFFICACY WITH NTM (M.TB HN878 P1) 8/1/2024 Â 7/31/2025 7/31/2025 OPTION 3 ACTIVITIES: EVALUATE OPTIMIZED M.TB VACCINE CANDIDATES FOR SAFETY, IMMUNOGENICITY AND EFFICACY IN THE NHP MODEL OF TB TASK 3.4: EX VIVO NHP MACROPHAGE STUDY TASK 3.4: ANALYZE THE EFFECTS THE DIFFERENT VACCINE STRATEGIES HAVE ON NONHUMAN PRIMATE (NHP) MACROPHAGE CONTROL OF AN EX VIVO M.TB INFECTION. IN EX VIVO EXPERIMENTS, RMR-VAMC WILL DETERMINE WHAT EFFECTS THE DIFFERENT VACCINATION STRATEGIES IN NHP HAVE ON THE ABILITY OF THEIR MACROPHAGES TO CONTROL AN EX VIVO INFECTION AND ON MACROPHAGE EFFECTOR FUNCTIONS. IN GROUPS OF NHP WITH DIFFERENT VACCINE STRATEGIES, PBMC WILL BE OBTAINED POST-BOOST AND SENT PRE-CHALLENGE AT 5 X
Denver Research Institute
Definitive Contract 75N93021C00029
$90.7k 11/30/24