Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=abstract
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=abstract", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=abstract", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=abstract", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=abstract" }, "data": [ { "type": "Grant", "id": "6431", "attributes": { "award_id": "3U19AI057229-17S1", "title": "Influenza responses and repertoire in vaccination, infection and tonsil organoids.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 21609, "first_name": "Chao", "last_name": "Jiang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-05-19", "end_date": "2022-03-31", "award_amount": 3874619, "principal_investigator": { "id": 21610, "first_name": "Mark Morris", "last_name": "Davis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Wuhan, China is the epicenter of a rapidly spreading pandemic the World Health Organization (WHO) has officially designated as COVID-19. COVID-19 is caused by SARS-CoV-2, but how it is spread from person to person is still unclear. The asymptomatic presentation of the disease, and widespread travel out of Wuhan have permitted its rapid dissemination. As of March 16, 2020, there are over 175,000 cases affecting 162 countries with over 6,700 fatalities worldwide. SARS-CoV-2 is positive-sense RNA virus infecting vertebrate hosts that exists in a group of closely related co-evolving entities of which two others – SARS-CoV and MERS-CoV – have caused recent epidemics. Due to the complexity of anti-viral immunity, experience with other viruses has shown that swift success in vaccine development is by no means assured. A major challenge is the difficulty in adequately characterizing T cell-mediated recognition of viral epitopes. Finding the major shared specificities in COVID-19 subjects will help us understand what the most important CD4+ and CD8+ T cell responses will be. These findings can be deployed to determine the optimal vaccine formulation so as to elicit these T cell specificities. We hypothesize that T cell responses to specific epitopes of SARS-CoV-2 will be critical for its control in infected patients across diverse HLA haplotypes, and that a comprehensive mapping of epitopes recognized by those who clear the virus and their cognate TCRs will facilitate the development of the most effective vaccines for COVID-19 treatment. To pursue this hypothesis, we will employ some very new tools for T cell responses that have recently been developed at Stanford and the Princess Margaret Cancer Center, together with COVID-19 survivors’ blood samples obtained in Toronto, Hong Kong and Stanford.", "keywords": [ "2019-nCoV", "Affect", "Affinity", "Aliquot", "Alleles", "Antigenic Specificity", "Antigens", "Asia", "Attention", "Avidity", "Basic Science", "Biological Assay", "Biotinylation", "Blood", "Blood Banks", "Blood Cells", "Blood specimen", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "COVID-19 vaccine", "Cancer Center", "Cell Line", "Cells", "Chemicals", "China", "Clinical Sciences", "Cloning", "Cohort Studies", "Common Epitope", "Complex", "Computer software", "Containment", "Country", "Cytometry", "Data", "Development", "Dextrans", "Disease", "Elements", "Enzymes", "Epidemic", "Epitope Mapping", "Epitopes", "European", "Ferritin", "Flow Cytometry", "Fluorescence-Activated Cell Sorting", "Freezing", "Frequencies", "Genetic Transcription", "Genotype", "Haplotypes", "Hong Kong", "Immunologic Monitoring", "Immunologics", "Immunology", "In Vitro", "Individual", "Infection", "Influenza", "Influenza vaccination", "Institutional Review Boards", "Interferon Type II", "Interleukin-2", "Interleukin-6", "Label", "Length", "Link", "Longitudinal cohort", "M. tuberculosis genome", "Maps", "Mediating", "Medical", "Memory", "Methods", "Middle East Respiratory Syndrome Coronavirus", "Noise", "Open Reading Frames", "Organoids", "Patients", "Peptide/MHC Complex", "Peptides", "Peripheral Blood Mononuclear Cell", "Persons", "Phase", "Phenotype", "Physiologic pulse", "Polymers", "Population", "Production", "Proteins", "Publishing", "RNA Viruses", "Reagent", "Regulatory T-Lymphocyte", "Reporter", "Research", "SARS coronavirus", "Sampling", "Serum", "Signal Transduction", "Site", "Source", "Specificity", "Stains", "Streptavidin", "Structure", "Survivors", "System", "T cell response", "T memory cell", "T-Cell Immunologic Specificity", "T-Cell Receptor", "T-Cell Receptor Genes", "T-Lymphocyte", "T-Lymphocyte Epitopes", "T-cell receptor repertoire", "Technology", "Therapeutic", "Time", "Tonsil", "Travel", "Vaccination", "Vaccines", "Viral", "Virus", "Work", "World Health Organization", "antiviral immunity", "base", "cell type", "cohort", "cytokine", "cytotoxicity", "experience", "fluorophore", "genomic platform", "high throughput screening", "improved", "magnetic beads", "member", "molecular sequence database", "mortality", "nanoparticle", "novel", "pandemic disease", "patient screening", "peripheral blood", "protein aminoacid sequence", "response", "single cell analysis", "single cell sequencing", "single-" ], "approved": true } }, { "type": "Grant", "id": "8715", "attributes": { "award_id": "1R43HL158345-01", "title": "Development of a CO2-bicarbonate combined membrane capture system for accessible treatment of acute respiratory failure.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 6344, "first_name": "Lora A.", "last_name": "Reineck", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-17", "end_date": "2022-05-31", "award_amount": 293121, "principal_investigator": { "id": 24500, "first_name": "Brian Yale", "last_name": "Chang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1741, "ror": "", "name": "X-COR THERAPEUTICS, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1741, "ror": "", "name": "X-COR THERAPEUTICS, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "X-COR Therapeutics is creating the first extracorporeal CO2 removal (ECCO2R) device that uses dialysis-like approaches to accessibly treat hypercapnic respiratory failure (HRF) patients. HRF is a devastating consequence of critical lung disease caused by chronic obstructive pulmonary disease (COPD) and other respiratory disorders including acute respiratory distress syndrome (ARDS), a common complication of COVID-19. The current standard of care for severe disease is invasive mechanical ventilation, which results in a ~30% mortality rate and increased susceptibility to ARDS. While use of protective ventilatory strategies reduces mortality, resultant hypercapnia from protective ventilation resembles diseases like COPD. In both cases, impaired ventilation causes increased carbon dioxide (CO2) levels that lead to acidosis, coma, and death. For patients with hypercapnia, extracorporeal technologies that deliver oxygen and remove gaseous CO2 (e.g. ECMO) present possible alternatives but are highly invasive and costly. They require high blood flow rates (>1 L/min) and large-bore cannula only deployable in specialized facilities. Here, we propose investigating a hybrid device that resembles a hemodialysis-like blood filtration cartridge that contains a novel configuration of two filtration fibers for bicarbonate dialysis and gaseous CO2 capture. High efficiency CO2 removal allows a low blood rate of <250 ml/min, thus allowing small catheters (<13.5 Fr) to replace the 28-30 Fr cannula used today in most extracorporeal therapies. Less invasive and standard vascular access makes this therapy accessible and enables its use in parallel with invasive mechanical ventilation. With parallel therapy, the proposed device can prevent hypercapnia that results from protective ventilation and enable safer use of invasive mechanical ventilation with earlier extubation. Because it can use existing hemodialysis systems, the device can be deployed with existing workflows and capital equipment. The objective of this Phase I SBIR project is to optimize and then investigate ventilatory benefits from using a hybrid membrane filtration device that removes CO2 from ultra-low extracorporeal blood flow. Aim 1 is to determine optimal device geometries and operating parameters (e.g. size, fiber pack density, and fiber ratio) that meet desired CO2 capture requirements through iterative modification of a novel design using scalable production methods. Each iteration will be evaluated using bench-top ex-vivo perfusion testing. Aim 2 is to investigate the impact that extracorporeal CO2 capture has on patient spontaneous and assisted ventilatory requirements using a series of physiologic computational models using patient-specific boundary conditions. Successful completion of this project will result in a manufacture-ready device with candidate geometries and operating parameters for pre-clinical testing. This device will be able to: 1) remove >30% of CO2 produced; 2) be produced using scalable manufacturing; and 3) be interoperable with existing hemodialysis platforms. This is a critical step for advancing toward future pre-clinical and clinical studies in support of FDA approval.", "keywords": [ "Acidosis", "Acute", "Acute respiratory failure", "Adoption", "Adult Respiratory Distress Syndrome", "Affect", "Alveolar", "Animal Model", "Bicarbonates", "Blood", "Blood Vessels", "Blood flow", "Blood gas", "COVID-19", "COVID-19 patient", "COVID-19/ARDS", "Cannulas", "Capital", "Carbon Dioxide", "Cardiopulmonary Physiology", "Catheters", "Cessation of life", "Characteristics", "Chronic Disease", "Chronic Obstructive Airway Disease", "Clinical", "Clinical Protocols", "Clinical Research", "Coma", "Complication", "Computer Models", "Custom", "Development", "Devices", "Dialysis procedure", "Disease", "Equilibrium", "Equipment", "Etiology", "Evaluation", "Excision", "Extracorporeal Membrane Oxygenation", "Fiber", "Filtration", "Future", "Geometry", "Goals", "Hemodialysis", "Hospitalization", "Hybrids", "Hypercapnia", "Hypercapnic respiratory failure", "Impairment", "Inflammation", "Intensive Care Units", "Investigation", "Ions", "Lead", "Liquid substance", "Lung", "Lung Compliance", "Lung diseases", "Maintenance", "Measurement", "Mechanical ventilation", "Mechanics", "Medical", "Medical emergency", "Membrane", "Methodology", "Methods", "Modification", "Morbidity - disease rate", "Outcome", "Oxygen", "Oxygenators", "Patient Selection", "Patients", "Performance", "Perfusion", "Phase", "Physiological", "Preclinical Testing", "Predisposition", "Production", "Protocols documentation", "Regulation", "Renal dialysis", "Resources", "Respiration Disorders", "Respiratory Failure", "Respiratory Insufficiency", "Risk", "Secondary to", "Selection Criteria", "Series", "Sheep", "Small Business Innovation Research Grant", "Support System", "System", "Techniques", "Technology", "Testing", "Therapeutic", "Treatment Failure", "Validation", "Venous", "Ventilator-induced lung injury", "blood filtration", "clinical efficacy", "clinically relevant", "clinically significant", "cost", "density", "design", "engineering design", "ex vivo perfusion", "interoperability", "interstitial", "lung injury", "mortality", "novel", "novel strategies", "physiologic model", "preclinical study", "prevent", "prototype", "research clinical testing", "respiratory", "severe COVID-19", "standard care", "standard of care", "tertiary care", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "15323", "attributes": { "award_id": "1R24GM154040-01", "title": "DIALS: supporting structural biology through open source diffraction processing software", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 11852, "first_name": "Anne", "last_name": "Gershenson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-20", "end_date": "2029-07-31", "award_amount": 1204713, "principal_investigator": { "id": 31918, "first_name": "Aaron Samuel", "last_name": "Brewster", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2533, "ror": "", "name": "UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "X-ray crystallography is a powerful tool for determining the atomic positions of proteins, used by researchers at synchrotrons and X-ray free electron lasers. Typically, the crystal is exposed to X-rays, which diffract and are collected on a detector to create diffraction patterns. These patterns are processed by software designed to seek out weak signal on the images and create datasets from which the protein structure can be solved. The DIALS diffraction data processing package is a mature product produced in collaboration between LBNL and Diamond Light Source (UK) that has primarily been supported in the US by research funding. DIALS is used at a number of synchrotrons world-wide for regular processing of user datasets and has been used at X- ray free electron lasers for fast processing of large datasets collected at hundreds to thousands of images per second. The program allows fast feedback of data quality when incorporated into automated processing that allows users to quickly make decisions about beamline operation and experimental direction. This has allowed researchers to produce high-impact structures in general biological fields, including human diseases such as COVID-19 and malaria, and energy research such as photosynthesis. This proposal would create a US R24 National Resource for the DIALS diffraction data processing package. The Resource would move DIALS funding in the US from primarily R01 research funding to a combination of separate research funding and operational funding from this proposal. The operational funding would be to support codebase optimization, maintenance, and refactoring, a build-and-release schedule, and new robust and adaptable user interfaces. Further, it would provide user outreach and training, both for general users, and through on-site training for beamline scientists to help with software integration into existing pipelines. The end result will be a well-maintained and documented software package used at synchrotrons and XFELs for routine data analysis without user intervention, and robust support for difficult cases.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14983", "attributes": { "award_id": "5S21MD018975-02", "title": "PREDICT (Precision Medicine, Education, Data Informatics and Community Translation) Institute", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6103, "first_name": "Nancy Lynne", "last_name": "Jones", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-06", "end_date": "2028-05-31", "award_amount": 2000000, "principal_investigator": { "id": 27778, "first_name": "Kathleen B.", "last_name": "Kennedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23397, "first_name": "Christopher", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 487, "ror": "https://ror.org/0085d9t86", "name": "Xavier University of Louisiana", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Xavier University of Louisiana seeks support from the NIH National Institute on Minority Health and Health Disparities to complement the research infrastructure in the College of Pharmacy through a new initiative. The proposed initiative will establish the Precision Medicine, Education, Data Informatics, and Community Translation (PREDICT) Institute, a comprehensive programmatic initiative creating a holistic and replicable framework for the utilization of electronic health data and community translation to affect the decision- making process to improve health outcomes. The Institute will extend the technical research exchange (TREX) program at Xavier to include training of current and future underrepresented researchers on health informatics best practices to diversify the research workforce and leverage community-based approaches to enhance clinical research efforts in vulnerable populations. This request comes at both a challenging and opportunistic time where an awareness of health disparities was heightened and, in some instances, exacerbated by the COVID-19 pandemic. The use of population health and bioinformatics data are potential tools useful in collective approaches required to achieve health equity. The Specific Aims of the PREDICT Institute are: Specific Aim #1: To enhance the existing Xavier health informatics infrastructure by increasing capacity for data acquisition, data warehousing, data access, data analytics, and technical assistance necessary for addressing health outcomes in minority communities. Specific Aim #2: To strengthen the research and outreach infrastructure of the university to promote community-engaged translational/clinical research and health promotion to mitigate health disparities. Specific Aim #3: To develop a diverse, highly competitive research workforce through the implementation of training/mentoring programs for students, postdoctoral residents/fellows, and early-stage/mid-career faculty (PREDICT scholars).", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11881", "attributes": { "award_id": "1S21MD018975-01", "title": "PREDICT (Precision Medicine, Education, Data Informatics and Community Translation) Institute", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6103, "first_name": "Nancy Lynne", "last_name": "Jones", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-06", "end_date": "2028-05-31", "award_amount": 2000000, "principal_investigator": { "id": 27778, "first_name": "Kathleen B.", "last_name": "Kennedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23397, "first_name": "Christopher", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 487, "ror": "https://ror.org/0085d9t86", "name": "Xavier University of Louisiana", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Xavier University of Louisiana seeks support from the NIH National Institute on Minority Health and Health Disparities to complement the research infrastructure in the College of Pharmacy through a new initiative. The proposed initiative will establish the Precision Medicine, Education, Data Informatics, and Community Translation (PREDICT) Institute, a comprehensive programmatic initiative creating a holistic and replicable framework for the utilization of electronic health data and community translation to affect the decision- making process to improve health outcomes. The Institute will extend the technical research exchange (TREX) program at Xavier to include training of current and future underrepresented researchers on health informatics best practices to diversify the research workforce and leverage community-based approaches to enhance clinical research efforts in vulnerable populations. This request comes at both a challenging and opportunistic time where an awareness of health disparities was heightened and, in some instances, exacerbated by the COVID-19 pandemic. The use of population health and bioinformatics data are potential tools useful in collective approaches required to achieve health equity. The Specific Aims of the PREDICT Institute are: Specific Aim #1: To enhance the existing Xavier health informatics infrastructure by increasing capacity for data acquisition, data warehousing, data access, data analytics, and technical assistance necessary for addressing health outcomes in minority communities. Specific Aim #2: To strengthen the research and outreach infrastructure of the university to promote community-engaged translational/clinical research and health promotion to mitigate health disparities. Specific Aim #3: To develop a diverse, highly competitive research workforce through the implementation of training/mentoring programs for students, postdoctoral residents/fellows, and early-stage/mid-career faculty (PREDICT scholars).", "keywords": [ "Address", "Affect", "Awareness", "Bioinformatics", "COVID-19 pandemic", "Clinical Research", "Communities", "Complement", "Data", "Data Analytics", "Decision Making", "Education", "Future", "Health", "Health Promotion", "Informatics", "Infrastructure", "Louisiana", "Mentors", "National Institute on Minority Health and Health Disparities", "Outcome", "Pharmacy facility", "Postdoctoral Fellow", "Process", "Public Health Informatics", "Reduce health disparities", "Research", "Research Infrastructure", "Research Personnel", "Students", "Time", "Training", "Translations", "United States National Institutes of Health", "Universities", "Vulnerable Populations", "college", "data access", "data acquisition", "data warehouse", "eHealth", "health data", "health disparity", "health equity", "improved", "informatics infrastructure", "mid-career faculty", "minority communities", "outreach", "population health", "precision medicine", "programs", "tool", "translational engagement" ], "approved": true } }, { "type": "Grant", "id": "12186", "attributes": { "award_id": "1R44AI179506-01", "title": "Novel, Self-Applied MicroArray Patch (MAP) of Zanamivir for Treatment of the Flu", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2024-01-31", "award_amount": 299999, "principal_investigator": { "id": 28055, "first_name": "Elke", "last_name": "Lipka", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2073, "ror": "", "name": "TSRL, INC.", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Yearly influenza epidemics strike millions of people, causing up to 500,000 deaths. Fatality caused by most seasonal influenza viruses is <0.03%, but with significant mortality in the young and the elderly populations. When a new pathogenic influenza strain enters the population, a pandemic could kill tens of millions of people with a negative economic impact estimated to be over 150 billion dollars. Due to the incomplete efficacy of the current vaccines, effective drug treatment is necessary. Presently, influenza treatment is only somewhat effective, and some influenza strains are resistant to the currently marketed therapeutics, adamantanes and the neuraminidase inhibitor Tamiflu®. However, while zanamivir (ZAN, Relenza®) remains highly active against oseltamivir-resistant influenza strains, its therapeutic impact is severely limited by its route of administration, via oral inhalation, which renders it unsuitable for patients with a compromised respiratory system. Therefore, development of a novel delivery alternative for ZAN as we propose here, is poised to address a significant unmet medical need. Transdermal drug delivery offers a number of improvements over other delivery systems. The drug directly enters the systemic circulation, circumventing absorption and first-pass barriers typical for oral delivery. It avoids skin puncture by syringe needles, eliminating pain and patient visits to a clinician. Transdermal delivery of ZAN could allow large numbers of patients to be reached during an influenza outbreak, which will be particularly important in light of the added risk during the ongoing COVID-19 pandemic. While ZAN itself cannot cross the human skin barrier at therapeutic rates, MicroArray Patch (MAP) - enhanced transdermal delivery is an elegant, efficient, and painless method for increasing the skin permeation of many drugs, including ZAN. Our novel drug-device combination product, TSR-066, consists of a swellable microneedle array, which will continuously deliver ZAN from a specially formulated reservoir over 5 days. This Fast-Track SBIR proposal will support optimization of the MAP with a focus on the applicator component and subsequent manufacturing of supplies for the Phase I clinical study. We have obtained agreement with the FDA on the preclinical studies needed in order to open the IND, as well as on the Phase I clinical development plans and the 505(b)2 regulatory strategy. In addition to the experimental work proposed here, we are developing a robust IP expansion strategy for TSR-066, as well as future product candidates that stand to benefit from MAP-enabled delivery. The end result of this work will be a novel, transdermal delivery approach for ZAN, which will expand its reach into patient groups for which Relenza® is contraindicated and allow for simple administration of ZAN for both treatment and prevention of the flu. We have assembled a team of expert advisors and collaborators to ensure successful completion of this research plan.", "keywords": [ "Achievement", "Acute", "Adamantane", "Address", "Agreement", "COVID-19 pandemic", "Cessation of life", "Circulation", "Clinical", "Clinical Research", "Communities", "Development", "Development Plans", "Devices", "Disease", "Drug Kinetics", "Effectiveness", "Elderly", "Ensure", "Epidemic", "Epithelium", "Family suidae", "Formulation", "Funding", "Future", "Grant", "Human", "Influenza", "Influenza prevention", "Inhalation", "Light", "Liquid substance", "Literature", "Lung", "Manufactured Supplies", "Marketing", "Medical", "Methods", "Miniature Swine", "Modeling", "Needles", "Neuraminidase inhibitor", "Oral", "Oseltamivir", "Pain", "Painless", "Pathogenicity", "Patients", "Persons", "Pharmaceutical Preparations", "Pharmacotherapy", "Phase", "Phase I Clinical Trials", "Plasma", "Population", "Powder dose form", "Publishing", "Puncture procedure", "Rattus", "Recommendation", "Reproducibility", "Research", "Resistance", "Respiratory System", "Risk", "Route", "Safety", "Seasons", "Self Administration", "Site", "Skin", "Small Business Innovation Research Grant", "Syringes", "System", "Therapeutic", "Toxicology", "Transdermal substance administration", "Vaccination", "Vaccines", "Visit", "Work", "absorption", "clinical development", "design", "economic impact", "effective therapy", "flu", "improved", "in vivo", "influenza epidemic", "influenza outbreak", "influenza virus strain", "influenzavirus", "manufacture", "mortality", "novel", "novel therapeutics", "pandemic disease", "patient population", "pre-Investigational New Drug meeting", "preclinical study", "prevent", "programs", "prototype", "resistant strain", "respiratory", "scale up", "seasonal influenza", "skin barrier", "skin irritation", "transmission process", "treatment adherence", "treatment duration", "vaccine effectiveness", "zanamivir" ], "approved": true } }, { "type": "Grant", "id": "15261", "attributes": { "award_id": "4R44AI179506-02", "title": "Novel, Self-Applied MicroArray Patch (MAP) of Zanamivir for Treatment of the Flu", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-16", "end_date": "2026-07-31", "award_amount": 999746, "principal_investigator": { "id": 28055, "first_name": "Elke", "last_name": "Lipka", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2073, "ror": "", "name": "TSRL, INC.", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Yearly influenza epidemics strike millions of people, causing up to 500,000 deaths. Fatality caused by most seasonal influenza viruses is <0.03%, but with significant mortality in the young and the elderly populations. When a new pathogenic influenza strain enters the population, a pandemic could kill tens of millions of people with a negative economic impact estimated to be over 150 billion dollars. Due to the incomplete efficacy of the current vaccines, effective drug treatment is necessary. Presently, influenza treatment is only somewhat effective, and some influenza strains are resistant to the currently marketed therapeutics, adamantanes and the neuraminidase inhibitor Tamiflu®. However, while zanamivir (ZAN, Relenza®) remains highly active against oseltamivir-resistant influenza strains, its therapeutic impact is severely limited by its route of administration, via oral inhalation, which renders it unsuitable for patients with a compromised respiratory system. Therefore, development of a novel delivery alternative for ZAN as we propose here, is poised to address a significant unmet medical need. Transdermal drug delivery offers a number of improvements over other delivery systems. The drug directly enters the systemic circulation, circumventing absorption and first-pass barriers typical for oral delivery. It avoids skin puncture by syringe needles, eliminating pain and patient visits to a clinician. Transdermal delivery of ZAN could allow large numbers of patients to be reached during an influenza outbreak, which will be particularly important in light of the added risk during the ongoing COVID-19 pandemic. While ZAN itself cannot cross the human skin barrier at therapeutic rates, MicroArray Patch (MAP) - enhanced transdermal delivery is an elegant, efficient, and painless method for increasing the skin permeation of many drugs, including ZAN. Our novel drug-device combination product, TSR-066, consists of a swellable microneedle array, which will continuously deliver ZAN from a specially formulated reservoir over 5 days. This Fast-Track SBIR proposal will support optimization of the MAP with a focus on the applicator component and subsequent manufacturing of supplies for the Phase I clinical study. We have obtained agreement with the FDA on the preclinical studies needed in order to open the IND, as well as on the Phase I clinical development plans and the 505(b)2 regulatory strategy. In addition to the experimental work proposed here, we are developing a robust IP expansion strategy for TSR-066, as well as future product candidates that stand to benefit from MAP-enabled delivery. The end result of this work will be a novel, transdermal delivery approach for ZAN, which will expand its reach into patient groups for which Relenza® is contraindicated and allow for simple administration of ZAN for both treatment and prevention of the flu. We have assembled a team of expert advisors and collaborators to ensure successful completion of this research plan.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "7278", "attributes": { "award_id": "3R01AI145835-01A1S1", "title": "Early and long term immunity following SARS-CoV-2 infection in humans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 12607, "first_name": "KAITLYN MELISSA", "last_name": "Morabito", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-01", "end_date": "2023-01-31", "award_amount": 338133, "principal_investigator": { "id": 7033, "first_name": "William", "last_name": "Messer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Yellow fever virus (YFV) is the prototype flavivirus and is historically the most important arthropod-borne viral pathogen of humans worldwide with ~200,000 infections annually and a mortality of ~50% in those who develop severe symptoms. YFV is endemic throughout Africa and South America and had been largely controlled through mass vaccination. The YFV vaccine 17D is considered one of the most effective live-attenuated virus (LAV) vaccines ever developed. Even so, every 10-year boosts have been recommended to maintain immunity. However, falling vaccination rates have led to a dramatic resurgence of disease in both Africa and South America, and subsequent vaccination campaigns have depleted the global supply of 17D. In response to these vaccine shortages, the WHO and CDC revised the 10-year boost to a once-in-a-lifetime vaccination recommendation, despite limited supporting data: although serosurveys find that ~90% of vaccinees have detectable neutralizing antibodies to YFV, careful review of these surveys finds that among individuals living in YFV non-endemic settings, at least 20% of YFV vaccinees lack detectable neutralizing antibodies at >10 years post-vaccination. While this finding must be critically evaluated in the context of ongoing outbreaks and vaccine shortages, it also represents a unique opportunity to study how 17D induces and maintains neutralizing antibodies in some vaccinees but not in others. Our central premise is that long-term YFV immunity is established by host immune activation in response to vaccine viremia at the time of vaccination: downstream effects of detectable differences in duration and magnitude of vaccine viremia at vaccination determine whether or not a vaccinee develops life-long immunity. We propose to evaluate this premise and its broader implications in three separate Aims: Aim 1 tests the hypothesis that vaccine viremia correlates with the long-term durability of of YFV neutralizing antibodies. We will enroll YFV pre-vaccinees and prospectively characterize acute vaccine viremia, acute innate immune and adaptive immune responses, and neutralizing antibody titers up to 5 years thereafter. Aim 2 tests the hypothesis that at least 20% of 17D vaccinated subjects will lose YFV immunity between 3- and 7-years post vaccination. We will recruit and prospectively follow a cohort of 17D vaccinees vaccinated 2-3 years prior to enrollment, comparing changes in YFV neutralizing antibodies and other immune markers over time and characterizing individual and cohort antibody decay kinetics. In Aim 3 we use 17D revaccination as a live-virus challenge to test the hypothesis that neutralizing antibody titers correlate with YFV protection. We will prospectively characterize pre-boost antibodies titers, vaccine viremia, acute immune responses and post-boost titers in vaccinees receiving boost 17D vaccinations. We expect to identify neutralizing antibody titers above which sterilizing immunity is conferred and titers below which it is not. These Aims will set a foundation for future studies to further dissect determinants of 17D and other LAV induced immunity and establish metrics that could allow efficient prioritization of 17D vaccination and optimize 17D use in the face of current and future outbreaks.", "keywords": [ "2019-nCoV", "Acute", "Africa", "Antibodies", "Antibody titer measurement", "Attenuated", "Attenuated Live Virus Vaccine", "Centers for Disease Control and Prevention (U.S.)", "Data", "Disease", "Disease Outbreaks", "Enrollment", "Evaluation", "Flavivirus", "Fostering", "Foundations", "Future", "Human", "Immune", "Immune response", "Immunity", "Immunologic Markers", "Individual", "Infection", "Kinetics", "Knowledge", "Life", "Mass Vaccinations", "Mission", "Recommendation", "Research", "South America", "Surveys", "Symptoms", "Testing", "Time", "United States National Institutes of Health", "Vaccinated", "Vaccination", "Vaccines", "Viremia", "Virus", "Yellow Fever Vaccine", "Yellow fever virus", "adaptive immune response", "arthropod-borne", "burden of illness", "cohort", "falls", "human pathogen", "immune activation", "innovation", "mortality", "neutralizing antibody", "pathogenic virus", "prospective", "prototype", "recruit", "response" ], "approved": true } }, { "type": "Grant", "id": "5938", "attributes": { "award_id": "3R01AI145835-02S1", "title": "Early and long term immunity following SARS-CoV-2 infection in humans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 20269, "first_name": "RUTH HUAB", "last_name": "Florese", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-01", "end_date": "2023-01-31", "award_amount": 191724, "principal_investigator": { "id": 20270, "first_name": "William", "last_name": "Messer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Yellow fever virus (YFV) is the prototype flavivirus and is historically the most important arthropod-borne viral pathogen of humans worldwide with ~200,000 infections annually and a mortality of ~50% in those who develop severe symptoms. YFV is endemic throughout Africa and South America and had been largely controlled through mass vaccination. The YFV vaccine 17D is considered one of the most effective live-attenuated virus (LAV) vaccines ever developed. Even so, every 10-year boosts have been recommended to maintain immunity. However, falling vaccination rates have led to a dramatic resurgence of disease in both Africa and South America, and subsequent vaccination campaigns have depleted the global supply of 17D. In response to these vaccine shortages, the WHO and CDC revised the 10-year boost to a once-in-a-lifetime vaccination recommendation, despite limited supporting data: although serosurveys find that ~90% of vaccinees have detectable neutralizing antibodies to YFV, careful review of these surveys finds that among individuals living in YFV non-endemic settings, at least 20% of YFV vaccinees lack detectable neutralizing antibodies at >10 years post-vaccination. While this finding must be critically evaluated in the context of ongoing outbreaks and vaccine shortages, it also represents a unique opportunity to study how 17D induces and maintains neutralizing antibodies in some vaccinees but not in others. Our central premise is that long-term YFV immunity is established by host immune activation in response to vaccine viremia at the time of vaccination: downstream effects of detectable differences in duration and magnitude of vaccine viremia at vaccination determine whether or not a vaccinee develops life-long immunity. We propose to evaluate this premise and its broader implications in three separate Aims: Aim 1 tests the hypothesis that vaccine viremia correlates with the long-term durability of of YFV neutralizing antibodies. We will enroll YFV pre-vaccinees and prospectively characterize acute vaccine viremia, acute innate immune and adaptive immune responses, and neutralizing antibody titers up to 5 years thereafter. Aim 2 tests the hypothesis that at least 20% of 17D vaccinated subjects will lose YFV immunity between 3- and 7-years post vaccination. We will recruit and prospectively follow a cohort of 17D vaccinees vaccinated 2-3 years prior to enrollment, comparing changes in YFV neutralizing antibodies and other immune markers over time and characterizing individual and cohort antibody decay kinetics. In Aim 3 we use 17D revaccination as a live-virus challenge to test the hypothesis that neutralizing antibody titers correlate with YFV protection. We will prospectively characterize pre-boost antibodies titers, vaccine viremia, acute immune responses and post-boost titers in vaccinees receiving boost 17D vaccinations. We expect to identify neutralizing antibody titers above which sterilizing immunity is conferred and titers below which it is not. These Aims will set a foundation for future studies to further dissect determinants of 17D and other LAV induced immunity and establish metrics that could allow efficient prioritization of 17D vaccination and optimize 17D use in the face of current and future outbreaks.", "keywords": [ "Acute", "Africa", "Antibodies", "Antibody titer measurement", "Attenuated", "Attenuated Live Virus Vaccine", "Centers for Disease Control and Prevention (U.S.)", "Data", "Disease", "Disease Outbreaks", "Enrollment", "Evaluation", "Flavivirus", "Fostering", "Foundations", "Future", "Human", "Immune", "Immune response", "Immunity", "Immunologic Markers", "Individual", "Infection", "Kinetics", "Knowledge", "Life", "Mass Vaccinations", "Mission", "Recommendation", "Research", "SARS-CoV-2 infection", "South America", "Surveys", "Symptoms", "Testing", "Time", "United States National Institutes of Health", "Vaccinated", "Vaccination", "Vaccines", "Viremia", "Virus", "Yellow Fever Vaccine", "Yellow fever virus", "adaptive immune response", "arthropod-borne", "burden of illness", "cohort", "falls", "human pathogen", "immune activation", "innovation", "mortality", "neutralizing antibody", "pathogenic virus", "prospective", "prototype", "recruit", "response", "serosurvey" ], "approved": true } }, { "type": "Grant", "id": "5117", "attributes": { "award_id": "3R01AI145835-03S1", "title": "Long Term Immunity Following Yellow Fever Vaccination", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 18228, "first_name": "RUTH HUAB", "last_name": "Florese", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-01", "end_date": "2023-01-31", "award_amount": 44999, "principal_investigator": { "id": 18229, "first_name": "William", "last_name": "Messer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Yellow fever virus (YFV) is the prototype flavivirus and is historically the most important arthropod-borne viral pathogen of humans worldwide with ~200,000 infections annually and a mortality of ~50% in those who develop severe symptoms. YFV is endemic throughout Africa and South America and had been largely controlled through mass vaccination. The YFV vaccine 17D is considered one of the most effective live-attenuated virus (LAV) vaccines ever developed. Even so, every 10-year boosts have been recommended to maintain immunity. However, falling vaccination rates have led to a dramatic resurgence of disease in both Africa and South America, and subsequent vaccination campaigns have depleted the global supply of 17D. In response to these vaccine shortages, the WHO and CDC revised the 10-year boost to a once-in-a-lifetime vaccination recommendation, despite limited supporting data: although serosurveys find that ~90% of vaccinees have detectable neutralizing antibodies to YFV, careful review of these surveys finds that among individuals living in YFV non-endemic settings, at least 20% of YFV vaccinees lack detectable neutralizing antibodies at >10 years post-vaccination. While this finding must be critically evaluated in the context of ongoing outbreaks and vaccine shortages, it also represents a unique opportunity to study how 17D induces and maintains neutralizing antibodies in some vaccinees but not in others. Our central premise is that long-term YFV immunity is established by host immune activation in response to vaccine viremia at the time of vaccination: downstream effects of detectable differences in duration and magnitude of vaccine viremia at vaccination determine whether or not a vaccinee develops life-long immunity. We propose to evaluate this premise and its broader implications in three separate Aims: Aim 1 tests the hypothesis that vaccine viremia correlates with the long-term durability of of YFV neutralizing antibodies. We will enroll YFV pre-vaccinees and prospectively characterize acute vaccine viremia, acute innate immune and adaptive immune responses, and neutralizing antibody titers up to 5 years thereafter. Aim 2 tests the hypothesis that at least 20% of 17D vaccinated subjects will lose YFV immunity between 3- and 7-years post vaccination. We will recruit and prospectively follow a cohort of 17D vaccinees vaccinated 2-3 years prior to enrollment, comparing changes in YFV neutralizing antibodies and other immune markers over time and characterizing individual and cohort antibody decay kinetics. In Aim 3 we use 17D revaccination as a live-virus challenge to test the hypothesis that neutralizing antibody titers correlate with YFV protection. We will prospectively characterize pre-boost antibodies titers, vaccine viremia, acute immune responses and post-boost titers in vaccinees receiving boost 17D vaccinations. We expect to identify neutralizing antibody titers above which sterilizing immunity is conferred and titers below which it is not. These Aims will set a foundation for future studies to further dissect determinants of 17D and other LAV induced immunity and establish metrics that could allow efficient prioritization of 17D vaccination and optimize 17D use in the face of current and future outbreaks.", "keywords": [ "Acute", "Address", "Adult", "Aedes", "Africa", "African", "Antibodies", "Antibody titer measurement", "Antibody-mediated protection", "Antigens", "Attenuated", "Attenuated Live Virus Vaccine", "Attenuated Vaccines", "Brazil", "Cells", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Country", "Cross-Sectional Studies", "Culicidae", "Data", "Dengue", "Disease", "Disease Outbreaks", "Dose", "Enrollment", "Evaluation", "Flavivirus", "Fostering", "Foundations", "Frequencies", "Future", "Heterogeneity", "Human", "Immune", "Immune response", "Immunity", "Immunologic Markers", "Individual", "Infection", "Kinetics", "Knowledge", "Life", "Long-Term Effects", "Mass Vaccinations", "Memory B-Lymphocyte", "Mission", "Modeling", "Nail plate", "Phase I/II Clinical Trial", "Policies", "Prospective Studies", "Public Health", "Recommendation", "Recording of previous events", "Research", "Safety", "South Africa", "South America", "Surveys", "Symptoms", "Testing", "Time", "United States National Institutes of Health", "Vaccinated", "Vaccination", "Vaccine Antigen", "Vaccinee", "Vaccines", "Viral Antibodies", "Viral Load result", "Viral Vaccines", "Viremia", "Virus", "Yellow Fever", "Yellow Fever Vaccine", "Yellow fever virus", "ZIKA", "Zika Virus", "adaptive immune response", "antibody detection", "arthropod-borne", "base", "burden of illness", "cohort", "critical period", "falls", "health organization", "human pathogen", "immune activation", "immunogenicity", "innovation", "mortality", "neutralizing antibody", "nonhuman primate", "pathogenic virus", "pressure", "prospective", "prototype", "recruit", "response", "secondary analysis", "seroconversion", "seropositive", "serosurvey" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1392, "count": 13920 } } }