Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&sort=-start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-start_date" }, "data": [ { "type": "Grant", "id": "15982", "attributes": { "award_id": "1R01AI189532-01A1", "title": "Biophysical constraints on antibody affinity maturation to SARS-CoV-2", "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": 32599, "first_name": "MICHELLE MARIE", "last_name": "ARNOLD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-19", "end_date": "2031-01-31", "award_amount": 815762, "principal_investigator": { "id": 44437, "first_name": "Angela Marie", "last_name": "Phillips", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The objective of this proposal is to develop a quantitative understanding of how the biophysical properties of antibodies impact their capacity to evolve affinity to divergent SARS-CoV-2 spike variants. Though there is substantial evidence that mutations acquired during affinity maturation impact antibody expression, affinity for distinct viral variants, and self-reactivity, we lack a quantitative understanding of (1) how mutations impact these biophysical properties and (2) how these properties, and trade-offs between them, collectively determine the fate of the corresponding B-cell lineage. Here, we propose three Aims to test our hypothesis that mutations differentially impact antibody expression, affinity, and self-reactivity, resulting in biophysical trade-offs that constrain the evolution of antibodies that bind divergent SARS-CoV-2 spike variants. In Aim 1, we quantitate the biophysical effects of mutations in anti-SARS-CoV-2 spike antibodies, using high-throughput mammalian cell- display methods we recently developed. By measuring the expression, affinity, and self-reactivity for millions of anti-spike antibodies, including broadly neutralizing antibodies (bnAbs) that bind divergent spike variants, their evolutionary predecessors, and systematically mutagenized antibody sequences, we will unveil biophysical constraints that shape affinity maturation to rapidly evolving viral antigens. In Aim 2, we evaluate the contributions of antibody biophysical properties to B-cell fitness, or proliferation, using longitudinally-sampled patient B-cells following exposure to divergent strains of SARS-CoV-2. This approach will reveal the relative importance of distinct antibody biophysical properties in driving B-cell evolutionary dynamics in human repertoires and enable development of quantitative models for predicting the outcomes of affinity maturation. In Aim 3, we define the impact of selection pressure during affinity maturation on the biophysical properties of the resulting antibodies, focusing on selection regimes known to favor the maturation of bnAbs that bind distinct spike variants. To this end, we leverage a B-cell directed evolution platform that mimics the mutagenic load of somatic hypermutation, enables fine-tuning of the antibody selection conditions, and supports longitudinal B-cell sampling to profile the evolutionary dynamics of the B-cell response and the biophysical properties of the corresponding antibody lineages. The resulting data will be used to define the impact of the selection regime on the biophysical determinants of B-cell fitness. Successful completion of these Aims will yield quantitative insight into (1) how antibody biophysical properties change during affinity maturation, (2) how they collectively determine B-cell fate in human repertoires, and (3) how their relative importance varies across distinct selection regimes. Thus, this work will advance our fundamental understanding of the biophysical mechanisms that shape antibody affinity maturation to rapidly evolving pathogens like SARS-CoV-2, supporting efforts to design and elicit antibodies that bind existing and novel viral variants.", "keywords": [ "2019-nCoV", "Affinity", "Antibodies", "Antibody Affinity", "Antibody Repertoire", "Antigens", "Autoantibodies", "Automobile Driving", "B-Cell Antigen Receptor", "B-Lymphocytes", "Binding", "Biophysical Process", "Biophysics", "Cell Lineage", "Cell membrane", "Cell surface", "Data", "Development", "Directed Molecular Evolution", "Engineering", "Epitopes", "Evolution", "Exposure to", "Frequencies", "Future", "Goals", "Human", "Immunoglobulin Somatic Hypermutation", "Knowledge", "Mammalian Cell", "Measures", "Membrane", "Methods", "Modeling", "Molecular", "Mutagens", "Mutation", "Outcome", "Patients", "Population", "Process", "Proliferating", "Property", "Protein Engineering", "Proteins", "Regimen", "Relaxation", "Research", "SARS-CoV-2 antibody", "SARS-CoV-2 exposure", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sampling", "Shapes", "Surface", "Testing", "Vaccines", "Variant", "Viral", "Viral Antigens", "Virus", "Work", "adaptive immunity", "antigen binding", "biophysical properties", "design", "efficacy evaluation", "empowerment", "fitness", "improved", "insight", "interest", "neutralizing antibody", "novel", "outcome prediction", "pathogen", "predictive modeling", "pressure", "response", "trafficking", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15972", "attributes": { "award_id": "1R01AI195981-01", "title": "Understanding programmed ribosomal frameshifting in coronaviruses", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-19", "end_date": "2031-01-31", "award_amount": 414029, "principal_investigator": { "id": 44426, "first_name": "Victoria Manuel", "last_name": "D'Souza", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3425, "ror": "", "name": "HARVARD UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronaviruses (CoV) are associated with severe diseases as demonstrated by the 2003 severe acute respiratory syndrome (SARS)-CoV1 epidemic and the SARS-CoV2 pandemic. One of the critical steps of infection involves viral mRNA mediated recoding of gene expression; a -1 frameshifting event that occurs during translation. It is this elegant mechanism that allows the ribosome to bypass a stop codon and synthesize viral enzymatic proteins. Furthermore, the frequency by which this event occurs is important for efficient viral infectivity and is regulated by domains in the translating mRNA (in the case of the SARS-CoV, this domain is a pseudoknot). Although structural studies of frameshifting have received considerable aOention and various structures have been proposed and solved, information on exactly which structure causes the frameshifting is lacking. Our preliminary studies indicate that CoV gene expression is regulated by a dynamic, proton-driven equilibrium between an active, and two inactive pseudoknot conformations that allows for strict control over the protein ratios. This proposal aims to gain a complete structural and mechanistic understanding of the frameshifting frequency in CoV by combining structural studies with biochemical and in vivo experiments. Our aims will be: (#1) to understand the basis for how the frameshifting frequency is maintained by engineering structure-guided mutants to test our equilibrium model, (#2) to determine the structures of the pseudoknot signal in both configurations: permissive and nonpermissive for frameshifting, and (#3) to determine the structure of ribosomes as they encounter the permissive conformation of the pseudoknot.", "keywords": [ "2019-nCoV", "Anti-viral Agents", "Biochemical", "Bypass", "COVID-19 pandemic", "Cell Line", "Characteristics", "Chemicals", "Code", "Complex", "Coronavirus", "Cryoelectron Microscopy", "Data", "Development", "Disease", "Engineering", "Equilibrium", "Event", "Frequencies", "Gene Expression", "Genetic", "In Vitro", "Infection", "Mediating", "Messenger RNA", "Molecular Conformation", "Mutation", "Nuclear Magnetic Resonance", "Nucleotides", "Outcome", "Population", "Preparation", "Process", "Proteins", "Protocols documentation", "Protons", "RNA", "Reading Frames", "Respiratory Disease", "Ribosomal Frameshifting", "Ribosomes", "SARS coronavirus", "Sampling", "Signal Transduction", "Structure", "Terminator Codon", "Testing", "Translating", "Translations", "Viral", "Virus", "Virus Replication", "conformer", "drug discovery", "equilibrium model", "experimental study", "in vivo", "insight", "live cell imaging", "mutant", "pandemic disease", "permissiveness", "protonation", "ribosome profiling", "sensor", "translation assay" ], "approved": true } }, { "type": "Grant", "id": "15970", "attributes": { "award_id": "1R01DK145476-01", "title": "Mechanisms of non-HIV Collapsing Glomerulopathy in Hispanic Patients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 44424, "first_name": "KEVIN E", "last_name": "CHAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-15", "end_date": "2030-11-30", "award_amount": 783899, "principal_investigator": { "id": 22546, "first_name": "Sumant Singh", "last_name": "Chugh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 804, "ror": "https://ror.org/01j7c0b24", "name": "Rush University Medical Center", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3423, "ror": "", "name": "RUSH UNIVERSITY MEDICAL CENTER", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Non-HIV collapsing glomerulopathy (CG) is a severe form of glomerular disease seen in all parts of the world. Major etiological factors include circulating proteins that cause recurrent CG, infections like SARS-CoV-2 and Parvovirus B19, drugs like pamidronate, and background genomic changes potentially present in any of the preceding categories. Whereas variants of the APOL1 gene have been implicated in select populations with West African heritage, a genomic basis in other patient populations has not been elucidated. Using data from two decades of investigations into CG centered around Hispanic patients from Mexico City and more recent genomic data from Peruvian Hispanic patients, several novel mechanistic rat and mouse models of CG were developed. Critical components of the CG upstream pathways are the podocyte expressed transcriptional factor ZHX2 and glomerular integrins, including α3β1 in the podocyte, αvβ5 in the glomerular endothelium, and αvβ3 at both locations. Finally, recombinant mutated human Angiopoietin-like 4 protein 8520 is known to have an integrin stabilizing effect specific to Integrins β1 and β5, and could be potentially used to treat CG in the future. The overall premise of this application is that high podocyte ZHX2 expression and low glomerular endothelial Integrin β5 expression predispose to the development of CG. In Aim 1, changes in glomeruli with high podocyte ZHX2 expression will be investigated using transgenic rat models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 2, changes in glomeruli with low endothelial Integrin β5 expression will be investigated using knockout mouse models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 3, rat and mouse models of CG will be treated with protein 8520 to test for prevention or improvement in CG, and to potentially halt the disease process before the development of collapse.", "keywords": [ "10 year old", "2019-nCoV", "8 year old", "ANGPTL4 gene", "APOL1 gene", "Admixture", "Adriamycin PFS", "Affect", "African American", "Albuminuria", "Apoptosis", "Binding", "Binding Proteins", "Blood capillaries", "COVID-19 pandemic", "CRISPR/Cas technology", "Categories", "Cell Membrane Proteins", "Cell Nucleus", "Cell membrane", "Cells", "Cities", "Cytoplasmic Tail", "Data", "Development", "Disease", "Down-Regulation", "Endothelium", "Environment", "Ephrin-B1", "Etiology", "Event", "Feedback", "Focal and Segmental Glomerulosclerosis", "Foot Process", "Future", "Genetic", "Genomics", "Glomerular Capillary", "High Prevalence", "Hispanic", "Hispanic Populations", "Homeobox", "Homeodomain Proteins", "Human", "Human Parvovirus B19", "ITGB3 gene", "Incubated", "Infection", "Integrins", "Investigation", "Kidney Diseases", "Knockout Mice", "Location", "Membrane", "Mexico", "Modeling", "Mus", "Mutate", "Nuclear", "Pathogenesis", "Pathway interactions", "Patients", "Pattern", "Peruvian", "Pharmaceutical Preparations", "Phase", "Population", "Prevention", "Process", "Proliferating", "Proteins", "Proteinuria", "Publishing", "Rat Transgene", "Rattus", "Recombinants", "Recurrence", "Renal glomerular disease", "Rodent", "Role", "Series", "Serum", "Signal Transduction", "Site", "Sprague-Dawley Rats", "Testing", "Therapeutic Agents", "Therapeutic Effect", "Upregulation", "Variant", "Virus Diseases", "WT1 gene", "West African", "Zinc Fingers", "cytokine release syndrome", "diabetic", "exome", "genetic variant", "genomic data", "genotyped patients", "glomerular endothelium", "glomerular function", "glutamyl aminopeptidase", "improved", "in vivo", "induced pluripotent stem cell", "insertion/deletion mutation", "migration", "mouse model", "nephrotoxicity", "novel", "overexpression", "pamidronate", "pathogen", "patient population", "podocyte", "post SARS-CoV-2 infection", "prevent", "rat parvovirus", "slit diaphragm", "therapeutic evaluation", "transcription factor", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15986", "attributes": { "award_id": "1R21AI185790-01A1", "title": "Lymphotoxin-dependent control of long COVID", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-13", "end_date": "2028-01-31", "award_amount": 234715, "principal_investigator": { "id": 7654, "first_name": "Alexei V", "last_name": "Tumanov", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3436, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 infection causes acute lung pathology and can lead to long-term complications, collectively known as long COVID. These complications include persistent pain, headaches, myalgia, and post-exertional malaise. However, the mechanisms behind these neurological symptoms remain poorly understood. In particular, the role of sensory neurons in the pathogenesis of long COVID is largely unexplored. This knowledge gap hinders the development of novel therapeutic strategies for managing neurological complications associated with long COVID. Animal models are essential for investigating the role of sensory neurons in SARS-CoV-2 infection and testing preclinical interventions. Unfortunately, existing mouse models that allow for the study of SARS-CoV-2 specific effects on sensory neurons in vivo are lacking. In our research, we found that wild-type mice infected with a mouse- adapted SARS-CoV-2 strain develop long-term pain. To further explore the role of sensory neurons in long COVID, we developed a mouse model with selective SARS-CoV-2 infection of sensory neurons through hACE2 expression in Nav1.8+ neurons. Additionally, we identified lymphotoxin beta receptor (LTβR) as a novel immune regulator of chronic pain following SARS-CoV-2 infection. The objective of this proposal is to investigate the role of LTβR signaling in sensory neurons in the pathogenesis of long COVID and to test the potential of LTβR antagonist to mitigate neurological complications of long COVID. Our central hypothesis is that LTβR signaling in sensory neurons promotes long COVID neurological symptoms which can be ameliorated by administration of LTβR antagonist. This hypothesis will be tested through two specific aims. In Aim 1, we will define the impact of LTβR signaling in sensory neurons on long COVID neurological symptoms, viral replication, and immune cell changes in sensory ganglia, using mice with selective LTβR inactivation in Nav1.8+ sensory neurons. In Aim 2, we will assess the therapeutic effects of LTβR antagonist in alleviating long COVID neurological symptoms and identify critical LTβR-dependent pathways in sensory ganglia using single-cell RNA sequencing. This proposal is innovative, significant and impactful, as it will elucidate the role of sensory neurons in long COVID pain, establish new animal models for studying long COVID, and evaluate the therapeutic potential of LTβR antagonists for treating SARS-CoV-2-induced neurological complications.", "keywords": [ "2019-nCoV", "ACE2", "Acute", "Address", "Affect", "Afferent Neurons", "Angiotensinogen", "Animal Model", "Automobile Driving", "COVID-19", "COVID-19 complications", "COVID-19 impact", "COVID-19 patient", "COVID-19 treatment", "CRISPR/Cas technology", "Cells", "Chimeric Proteins", "Data", "Development", "Disease", "Enzymes", "Exertion", "Exhibits", "Filament", "Genetic", "Goals", "Hand Strength", "Headache", "Human", "Hypersensitivity", "Immune", "Immunohistochemistry", "Immunomodulators", "Impairment", "Individual", "Infection", "Intervention", "Kinetics", "Knowledge", "Ligands", "Light", "Long COVID", "Malaise", "Measures", "Modeling", "Mus", "Myalgia", "Neuroglia", "Neuroimmunomodulation", "Neurologic", "Neurologic Dysfunctions", "Neurologic Symptoms", "Neuronal Plasticity", "Neurons", "Nociceptors", "Pain", "Pain management", "Pathogenesis", "Pathway interactions", "Peripheral", "Peripheral Nervous System Diseases", "Persistent pain", "Play", "Preclinical Testing", "Public Health", "Pulmonary Pathology", "Quality of life", "Receptor Inhibition", "Receptor Signaling", "Recombinants", "Research", "Role", "SARS-CoV-2 infection", "SCN2A protein", "Sensory Ganglia", "Signal Transduction", "Spinal Ganglia", "Structure of trigeminal ganglion", "Study models", "Symptoms", "Testing", "Therapeutic", "Therapeutic Effect", "Therapeutic Intervention", "Time", "Tumor Necrosis Factor Receptor", "Tumor Necrosis Factor-Beta", "Venus", "Virus", "Virus Replication", "Wild Type Mouse", "antagonist", "behavior change", "behavior test", "brain fog", "chemotherapy", "chronic pain", "efficacy testing", "immune activation", "in vivo", "innovation", "insight", "lymphotoxin beta receptor", "mechanical allodynia", "member", "mouse model", "new therapeutic target", "novel", "novel therapeutic intervention", "pain reduction", "painful neuropathy", "post SARS-CoV-2 infection", "pre-clinical", "response", "single-cell RNA sequencing", "transcriptomics", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15988", "attributes": { "award_id": "1R01AI189680-01A1", "title": "Mechanisms of simian arterivirus entry, immune evasion, and zoonotic potential", "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": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-09", "end_date": "2031-01-31", "award_amount": 790507, "principal_investigator": { "id": 24434, "first_name": "Cody Jay", "last_name": "Warren", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1583, "ror": "", "name": "UNIVERSITY OF COLORADO", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3438, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Many emerging zoonotic viruses (animal viruses that transmit to humans) are highly pathogenic, having the potential to cause deadly epidemics or even global pandemics. The risks zoonotic viruses pose are highlighted by the emergence of the SARS/MERS coronaviruses, Ebola virus, and HIV-1, all of which are related to animal viruses that were unknown before they caused substantial cases of disease in humans. Given the risk animal viruses pose to humans, many researchers have turned to viral discovery—using genome sequencing tools and metagenomic analyses, researchers hope to identify novel animal viruses before they emerge in humans. We've developed a pipeline that integrates viral surveillance with molecular investigations in the laboratory to identify pre-emergent viruses with epidemic potential. Using this approach, we've provided compelling evidence suggesting that simian arteriviruses (SAVs)—understudied and neglected pathogens of African monkeys—are poised for spillover, posing a threat to human health. We demonstrate key biological features that poise SAVs for zoonosis, including: (1) compatibility with human receptors; (2) high titer propagation in human cells; and (3) potential for evasion of human innate immunity. Further interrogation of the biology of SAV infection is crucial for future epidemic preparedness efforts. The objective of this proposal is to uncover mechanisms of cell entry, immune evasion, and zoonotic potential for these highly concerning viral pathogens. In Aim 1, we employ a series of molecular, biochemical, structural, and functional approaches to define SAV-receptor interactions and establish proof-of-concept strategies for future therapeutics—an essential step in outbreak preparedness. In Aim 2, we will identify SAV proteins that antagonize the human innate immune response, with the goal of revealing vulnerabilities that may help develop safe and effective antiviral approaches. In Aim 3, we will thoroughly evaluate the zoonotic potential of diverse SAVs. This includes: (1) identifying novel SAVs through whole virome sequencing of wild African primate biomaterials; (2) the development and application of non-human primate induced-pluripotent stem cell (iPSC)-derived macrophages to isolate novel SAVs in cell targets from natural host species; and (3) detailed infection studies in human cells to evaluate human compatibility. Further, we will perform the first in-depth serosurvey for SAV exposure history using banked sera from a Ugandan case-control cohort. When taken together, this proposal will lead to a deeper understanding of the molecular biology and pathogenesis of these understudied viruses, as well as a greater appreciation for the zoonotic risk that they pose. It is imperative that we invest in characterizing the biology and pathogenesis of SAVs now so that we may begin to develop platform technologies (i.e., diagnostics, vaccines, therapeutics) in case they do emerge in the future.", "keywords": [ "2019-nCoV", "African", "Animals", "Arterivirus", "Arterivirus Infections", "Binding", "Biochemical", "Biocompatible Materials", "Biological", "Biology", "Blocking Antibodies", "Case/Control Studies", "Cells", "Collection", "Communities", "Complex", "Cryoelectron Microscopy", "Cytokine Signaling", "Dedications", "Development", "Diagnostic", "Disease", "Ebola virus", "Endocytosis", "Epidemic", "Evaluation", "Family", "Frequencies", "Future", "Glycoproteins", "Goals", "HIV-1", "HIV/AIDS", "Health", "Human", "Human Cell Line", "Immune", "Immune Evasion", "Infection", "Influenza A Virus H1N1 Subtype", "Innate Immune Response", "Innate Immune System", "Integration Host Factors", "Interferons", "Investigation", "Investments", "Kinetics", "Knowledge", "Laboratories", "Macrophage", "Membrane Fusion", "Metagenomics", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Molecular", "Molecular Biology", "Monkey Hemorrhagic Disease Virus", "Monkeys", "Mutation", "Natural Immunity", "Nonstructural Protein", "Pathogenesis", "Pathogenicity", "Population Research", "Primates", "Process", "Proteins", "Recording of previous events", "Research", "Research Personnel", "Resources", "Risk", "Role", "Series", "Severe Acute Respiratory Syndrome", "Structure", "Therapeutic", "Vaccines", "Viral", "Viral Hemorrhagic Fevers", "Virus", "Virus Diseases", "Virus Integration", "Virus Receptors", "Virus Replication", "Zoonoses", "antagonist", "case control", "cohort", "emerging virus", "epidemic potential", "epidemic preparedness", "future epidemic", "genome sequencing", "induced pluripotent stem cell", "influenzavirus", "insight", "neglect", "nonhuman primate", "novel", "outbreak preparedness", "pandemic disease", "pathogen", "pathogenic virus", "receptor", "repeat offender", "response", "serosurvey", "technology platform", "tool", "viral transmission", "virome" ], "approved": true } }, { "type": "Grant", "id": "15976", "attributes": { "award_id": "1R21AI190571-01A1", "title": "Statistical Methods for Assessing Immune Correlates of Risk and Protection Using Flexible Two-Phase Sampling Designs that Enrich Longitudinal Samples", "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": 32873, "first_name": "MISRAK", "last_name": "GEZMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-09", "end_date": "2028-01-31", "award_amount": 220000, "principal_investigator": { "id": 44430, "first_name": "Youyi", "last_name": "Fong", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44431, "first_name": "Ying", "last_name": "Huang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2062, "ror": "", "name": "FRED HUTCHINSON CANCER CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Immune correlates of protection (CoP) are biomarkers that predict vaccine-induced protection against dis- eases and play a crucial role in the design and development of effective vaccines. The U.S. government (USG)-led initiative to identify CoPs for COVID vaccines highlighted the importance of neutralizing antibody titers as surrogate endpoints, significantly impacting vaccine recommendations and approvals. To effec- tively measure these immune biomarkers, researchers utilize two-phase designs, such as case-cohort or case-control studies, to boost statistical power and enhance representation. This proposal aims to develop novel two-phase sampling designs that allow enrichment of longitudinal immune response marker mea- surements in immune correlates studies. The proposal also aims to develop advanced statistical methods for datasets collected under sampling designs that would introduce bias if analyzed using conventional in- verse probability-weighted methods. Aim 1 focuses on the analysis of the immune response biomarkers measured at the peak immunogenicity time point, while Aim 2 delves into the study of the decaying im- mune response biomarkers. The final product will feature a user-friendly software implementation of the proposed methods, along with its application to analyze COVID correlates datasets from past and ongoing USG-sponsored vaccine efficacy trials.", "keywords": [ "Acceleration", "Adult", "Advisory Committees", "Antibodies", "Antibody titer measurement", "Authorization documentation", "COVID-19", "COVID-19 vaccine", "Case/Control Studies", "Child", "Clinical Data", "Communicable Diseases", "Correlation Studies", "Cost Measures", "Data Correlations", "Data Set", "Development", "Disease", "Future", "Government", "Immune", "Immune System Diseases", "Immune response", "Immunologic Markers", "Infection", "Institution", "Length", "Longitudinal Studies", "Measurement", "Measures", "Methodology", "Methods", "Onset of illness", "Participant", "Phase", "Placebos", "Play", "Probability", "RNA vaccine", "Randomized", "Recommendation", "Research", "Research Personnel", "Resources", "Risk", "Role", "Sampling", "Sampling Biases", "Sampling Studies", "Security", "Series", "Statistical Methods", "Structure", "Surrogate Endpoint", "Techniques", "Time", "Vaccination", "Vaccines", "Visit", "Work", "booster vaccine", "case control", "cohort", "design", "disorder prevention", "disorder risk", "efficacy trial", "flexibility", "global health", "immunogenicity", "immunological status", "improved", "innovation", "interest", "meetings", "neutralizing antibody", "novel", "novel vaccines", "participant enrollment", "predictive marker", "programs", "rational design", "response biomarker", "software development", "time to event", "trial enrollment", "user friendly software", "user-friendly", "vaccine development", "vaccine efficacy", "vaccine platform", "vaccine-induced immunity", "vaccinology" ], "approved": true } }, { "type": "Grant", "id": "15975", "attributes": { "award_id": "1R01AI195779-01", "title": "Regulatory T cell memory in human tissues", "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": 44428, "first_name": "CHAO", "last_name": "JIANG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2030-01-31", "award_amount": 3144408, "principal_investigator": { "id": 7597, "first_name": "Donna L.", "last_name": "Farber", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 44429, "first_name": "Peter Alan", "last_name": "Sims", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "T cell memory is stored across heterogeneous subsets with diverse functions in both tissues and circulation. While most studies have focused on the pro-inflammatory and cytotoxic functions of memory T cells, regulatory T cells (Tregs) serve an equally important immunomodulatory role in memory responses, particularly in tissues. While specific roles for Tregs in establishing tolerance and promoting tissue homeostasis have been elucidated in mouse models, the role of human Tregs in healthy immune responses and protective immunity in vivo has been difficult to assess. Moreover, the identity and function of human Tregs in diverse tissues remains unknown. We have established an organ donor tissue resource for human immunology that has allowed us to profile antigen-specific T cells across human tissues. Through these efforts, we found that antigen-specific Tregs are substantially enriched among memory T cells that respond to antigens from multiple viruses, including SARS-CoV-2, influenza, and EBV, and are particularly enriched in lymph nodes, spleen and lungs compared to blood, bone marrow and other sites. In addition, we found that memory Tregs induce an activation program that is distinct from effector memory T cells (TEM) involving CCL17 as a novel Treg-derived cytokine not produced by TEM cells or any other T cell subset. Moreover, tissue memory Tregs exhibit clonal overlap with TEM cells within and between sites. These findings raise the possibility that memory Tregs are generated along with TEM during priming and that they share a common pre-cursor with TEM. In the proposed studies, we will pursue three aims: 1) Determine the role of antigen and tissue in memory Treg induction; 2) Define the clonal and migratory relationships (i.e. tissue distributions) between memory Treg and other memory subsets; 3) Elucidate the functional and spatial interactions of tissue Tregs with immune and structural cells in the lymph node. We will combine state-of-the-art technologies for single-cell and spatial profiling with our unique human tissue resource to elucidate mechanisms for the generation, function, and maintenance of memory Tregs in human tissues. The results from this study will be important for designing strategies to promote immunoregulation and tissue repair for protective immunity and can inform Treg-directed therapies for autoimmunity and transplantation.", "keywords": [ "2019-nCoV", "Adult", "Affect", "Age", "Allergens", "Antigens", "Autoantigens", "Autocrine Communication", "Autoimmunity", "Blocking Antibodies", "Blood", "Bone Marrow", "CCL17 gene", "CCR8 gene", "COVID-19", "Cell Communication", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Chemotaxis", "Circulation", "Cytoprotection", "Drug or chemical Tissue Distribution", "Environment", "Exhibits", "FOXP3 gene", "Fatty acid glycerol esters", "Frequencies", "Gene Expression", "Gene Expression Profile", "Generations", "Homeostasis", "Homing", "Human", "Human Herpesvirus 4", "Human Resources", "IL2RA gene", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunology", "In Situ", "Individual", "Infection", "Inflammation", "Inflammatory", "Influenza", "Life", "Lung", "Lymphoid Tissue", "Maintenance", "Mediating", "Memory", "Mucous Membrane", "Mus", "Muscle", "Organ Donor", "Pathway interactions", "Phenotype", "Play", "Population", "Proteins", "RNA vaccine", "Regulation", "Regulatory T-Lymphocyte", "Research", "Role", "SARS-CoV-2 infection", "Signal Transduction", "Site", "Slice", "Spleen", "Stromal Cells", "T cell differentiation", "T cell therapy", "T memory cell", "T-Cell Activation", "T-Lymphocyte", "T-Lymphocyte Subsets", "Technology", "Thymus Gland", "Tissues", "Transplantation", "Vaccines", "Virus", "Virus Diseases", "age related changes", "antigen-specific T cells", "cell motility", "chemokine", "cytokine", "cytotoxic", "design", "human tissue", "immunoregulation", "in vivo", "lymph nodes", "lymphoid organ", "memory CD4 T lymphocyte", "mouse model", "multimodality", "novel", "pathogen", "programs", "receptor", "recruit", "response", "single cell technology", "tissue repair", "tissue resident memory T cell", "tissue resource", "transcription factor", "tumor" ], "approved": true } }, { "type": "Grant", "id": "15974", "attributes": { "award_id": "1R01AI191417-01A1", "title": "MARVELOUS: Maternal RSV Vaccination- Evaluating Optimal Immune Responses", "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": 44292, "first_name": "MERCY R", "last_name": "PRABHUDAS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2030-01-31", "award_amount": 3859259, "principal_investigator": { "id": 21683, "first_name": "Andrea Goldberg", "last_name": "Edlow", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22942, "first_name": "SABRA L.", "last_name": "KLEIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, { "id": 44427, "first_name": "Liza", "last_name": "Konnikova", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3427, "ror": "", "name": "MASSACHUSETTS GENERAL HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent approval of the Respiratory Syncytial Virus (RSV) vaccine for administration in pregnancy presents a novel opportunity to define immune responses of the maternal-fetal dyad, and how that response crosses the placenta and mammary tissue. Recent work indicates that timing of maternal RSV vaccination alters placental antibody transfer to the fetus. To maximize infant protection after maternal RSV vaccination, key gaps in knowledge include: 1. The extent to which maternal vaccination elicits direct fetal antigen-agnostic and antigen- specific cellular responses to augment infant protection from RSV and other infections. 2. How gestational age at vaccination alters maternal antibody response, subsequent placental and breastmilk antibody transfer, and persistence of immunity in the infant. The proposed studies will test the central hypothesis that timing of maternal vaccination, antibody Fc-receptor binding properties, glycosylation profiles, neutralizing antibody levels and non-neutralizing antibody functions are all key determinants of placental and breastmilk antibody transfer to the neonate. These antibody features will work in concert with fetal innate and adaptive immune responses to maternal vaccination, driving protection of the infant through 6 months of age. In a cohort of 400 pregnant women and their infants, this study will examine fetal cellular responses to maternal RSV vaccination, both RSV-agnostic and RSV-specific, by evaluating fetal immune cells isolated from placental villi and cord blood (Aim 1). It will comprehensively profile placentally- and breastmilk-transferred antibodies after RSV vaccination in pregnancy, evaluating IgG subclass, Fc-receptor binding, glycosylation profile, and neutralizing capacity of antibodies using in vivo and in vitro assays (Aim 2). It will then evaluate how antibody properties and timing of maternal vaccination impact the durability of antibody-mediated and cellular immunity in infant blood and breastmilk, through 6 months of age (Aim 3). Machine learning approaches will be used to estimate the magnitude and specific features of protective immune responses induced by maternal vaccination, not only for RSV, but also for influenza, Tdap, and COVID-19. These methods will generate a comprehensive model of durable infant protection from maternal vaccination spanning multiple pathogens. Defining these immune principles across the maternal-fetal dyad will generate key biological insights necessary to optimize neonatal and infant protection.", "keywords": [ "3-Dimensional", "Address", "Age Months", "Antibodies", "Antibody Response", "Antibody-mediated protection", "Antigens", "Automobile Driving", "Biological", "Biological Assay", "Blood", "Breast", "Breast Epithelial Cells", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Separation", "Cells", "Cellular Immunity", "Characteristics", "Chorionic villi", "Clinical Trials", "Clonal Expansion", "Colostrum", "Data", "Disease", "Ensure", "Fc Receptor", "Fetus", "Future", "Gene Expression Profile", "Gestational Age", "Human Milk", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin G", "In Vitro", "Infant", "Infection", "Influenza", "Innate Immune Response", "Knowledge", "Life", "Longevity", "Machine Learning", "Maternal antibody", "Measures", "Mediating", "Memory", "Methods", "Milk", "Modeling", "Mononuclear", "Mothers", "Nature", "Neonatal", "Peptides", "Pertussis", "Phase III Clinical Trials", "Phenotype", "Placenta", "Plasma", "Polysaccharides", "Pregnancy", "Pregnant Women", "Premature Birth", "Property", "Prospective cohort", "Recommendation", "Respiratory Syncytial Virus Vaccines", "Respiratory syncytial virus", "Serology", "System", "T cell response", "T memory cell", "T-Lymphocyte", "Testing", "Time", "Tissues", "Training", "Umbilical Cord Blood", "Vaccinated", "Vaccination", "Vaccine Design", "Vaccines", "Work", "adaptive immune response", "anti-influenza", "antibody test", "antibody transfer", "cohort", "embryo/fetus antigen", "emerging pathogen", "experimental study", "fetal", "fetal immunity", "glycosylation", "immune function", "in vitro Assay", "in vivo", "infant morbidity", "infant morbidity/mortality", "insight", "large datasets", "machine learning method", "machine learning model", "mammary", "maternal vaccination", "neonatal immunity", "neonate", "neutralizing antibody", "novel", "pathogen", "placental transfer", "predictive modeling", "prenatal exposure", "receptor binding", "respiratory pathogen", "response", "sex", "transcytosis", "unvaccinated", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15980", "attributes": { "award_id": "1R01AI189659-01A1", "title": "Durable and broad airway immunity through next-generation intranasal boosters", "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": 32831, "first_name": "JENNIFER L", "last_name": "GORDON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2031-01-31", "award_amount": 662465, "principal_investigator": { "id": 44435, "first_name": "David R.", "last_name": "Martinez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3431, "ror": "", "name": "YALE UNIVERSITY", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Intramuscular SARS-CoV-2 mRNA-LNP do not reliably nor durably elicit respiratory mucosal IgA. Moreover, vaccinated individuals who become infected are more durably protected and this is thought to be mediated by respiratory mucosal IgA. Currently, there are no mucosal respiratory vaccines for human use. We identified a mucosal booster vaccine admixed with a mast cell agonist adjuvant, mastoparan-7, and a toll-like receptor 9 agonist adjuvant, CpG, that elicits durable mucosal IgA. Importantly, mice intranasally boosted with a multivalent nanoparticle vaccine adjuvanted with mastoparan-7 and CpG are protected from bat SARS-like virus challenge. We propose to study the mechanism of mast cell and antigen-presenting cell signaling modulated by this novel mucosal adjuvant combination. We will pursue our central objective which is to understand how mucosal IgA is elicited and maintained following respiratory mucosal vaccination with our exciting universal vaccines to ultimately achieve durable and broadly protective immunity against zoonotic coronaviruses. To achieve this objective, we will complete these aims: Aim 1: Test the hypothesis that mast cells and antigen-presenting cells elicit specific cytokines and chemokines that modulate durable IgA. We propose to study the impact of intranasal boost dose and interval on IgA kinetics and durability. We will also define if the mastoparan-7 and CpG adjuvant combination requires mast cell and antigen presenting cells that signal through CpG via the TLR-9 pathway. We will then define gene expression profiles from respiratory tract mast cells and antigen presenting cells that are activated by mastoparan-7 and CpG and modulate durable mucosal IgA responses. Aim 2: Test the hypothesis that M7/CpG nanoparticle vaccine elicits durable IgA secreting cells and IgA memory B cells in the respiratory tract using lineage-tracing, fluorescent reporter mice pre- immune with common-cold CoV. We will determine how intranasal boosting modulates IgA-secreting plasma cells and IgA memory B cells that home back to the respiratory mucosa in SARS-CoV-2 immune mice and in mice immune against common-cold coronaviruses. We will use cre-lox inducible, IgA-secreting cell and IgA memory B cell fluorescent reporter mice to define how intranasal boosting modulates mucosal IgA immunity. We will also test adjuvant and intranasal safety using a human lymph node organoid model from upper- respiratory tract draining lymph tissue from humans. Aim 3: Test the hypothesis that durable mucosal IgA can protect against transmissible SARS-CoV-2 variants in hamster transmission models and protect against SARS-related coronaviruses. We will determine if the mastoparan-7 and CpG adjuvanted nanoparticle intranasal booster reduces transmission of SARS-CoV-2 variants in hamster models. We will also use IgA knockout mice to determine if IgA is required for protection against SARS-like viruses.", "keywords": [ "2019-nCoV", "Adjuvant", "Agonist", "Antigen Targeting", "Antigen-Presenting Cells", "Antigens", "B-Lymphocytes", "Back", "COVID-19 vaccine", "Cell Degranulation", "Cell secretion", "Chiroptera", "Common Cold", "Coronavirus", "Coupled", "Data", "Disease", "Dose", "Ferritin", "Frequencies", "Gene Expression Profile", "Generations", "Genes", "Goals", "Hamsters", "Health", "Home", "Human", "Immune", "Immune response", "Immune signaling", "Immunity", "Immunobiology", "Immunoglobulin A", "Immunologics", "Intramuscular", "Intranasal Administration", "Kinetics", "Knockout Mice", "Knowledge", "Length", "Lineage Tracing", "Lymph", "Mediating", "Memory B-Lymphocyte", "Messenger RNA", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mucosal Immunity", "Mucous Membrane", "Mus", "Organoids", "Pathogenicity", "Pathway interactions", "Patients", "Peptides", "Plasma Cells", "RNA vaccine", "Receptor Signaling", "Reporter", "Respiration", "Respiratory Mucosa", "Respiratory System", "SARS coronavirus", "SARS-CoV-2 transmission", "SARS-CoV-2 variant", "Safety", "Severe Acute Respiratory Syndrome", "Signal Transduction", "TLR9 gene", "Tamoxifen", "Testing", "Upper respiratory tract", "Vaccinated", "Vaccination", "Vaccine Adjuvant", "Vaccinee", "Vaccines", "Virus", "Work", "Zoonoses", "antiviral immunity", "booster vaccine", "chemokine", "coronavirus vaccine", "cross immunity", "cytokine", "experimental study", "gene panel", "human tissue", "lipid nanoparticle", "lymph nodes", "mast cell", "mastoparan", "mucosal vaccination", "mucosal vaccine", "nanoparticle", "next generation", "novel", "novel coronavirus", "pandemic disease", "preclinical safety", "respiratory", "respiratory virus", "response", "single-cell RNA sequencing", "tool", "transmission process", "universal vaccine", "vaccine evaluation", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "15977", "attributes": { "award_id": "1R21AI196845-01", "title": "Rapid point-of-care diagnosis of symptomatic and asymptomatic herpes infection", "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": 44432, "first_name": "JONATHAN A", "last_name": "GLOCK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2028-01-31", "award_amount": 427625, "principal_investigator": { "id": 4494, "first_name": "Ronit", "last_name": "Fraiman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3428, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Herpes simplex virus (HSV) is highly contagious and can be transmitted via physical contact. HSV can be diagnosed by detecting the presence of the virus in lesions or the antibodies in the blood. Yet, viral shedding can happen from asymptomatic infections, highlighting the need for early and accurate detection of HSV to prevent transmission. The most common ways to detect HSV are nucleic acid testing of an active infection via qPCR or serological testing of antibody levels in patient serum. However, qPCR is only accurate if a person is symptomatic and in asymptomatic people both the FDA and the CDC recommend against serological testing due to issues with sensitivity. Additionally, current testing for CNS complications arising from HSV infections requires highly invasive cerebral spinal fluid (CSF) sampling to diagnose. Thus, rapid, accessible, sensitive, and accurate point- of-care tests are in dire need. In 2021, we published a watershed paper describing how we can leverage cell surface glycans that the SARS- CoV-2 virus uses to bind and infect cells, to capture it onto rapid test strips for sensitive detection of the virus (Kim et al, ACS Central Science). Inspired and motivated by our success with SARS-CoV-2 sensing, we propose a novel lateral flow strip assay (LFSA) device for rapid and reliable point-of-care antigen-based detection capable of differentiating between HSV-1 and HSV-2 infections and sensing of CNS complications through serum. As cell surface proteoglycans such as heparan sulfate play an important role in the binding and cell entry of HSV, we will leverage it as a universal binder and use type specific cell receptors to distinguish between HSV strains (Specific Aim 1). Higher selectivity will be achieved by exploring sensitivity to sulfonation of heparan sulfate and other glycocalyx proteins. Sensor performance will be evaluated in complex fluids such as human genital fluids or saliva, and in genital washings of HSV-infected mice. To enhance our ability to identify and subtype HSV, we will engineer tailored cell membranes to optimize their interactions with viral envelope proteins, and strip and print these cell-derived membranes on paper test strips in Specific Aim 2. In Specific Aim 3, we will develop a blood test for the rapid quantitative screening of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), upregulated biomarkers upon CNS damage. We will incorporate electrochemical signals for quantitative assessment. This Bluetooth device will enable early and fast triage of patients for further screening. Together, these devices will enable us rapid and cost-effective screening of high-risk populations, accurate subtyping, and a swift connection of patients with treatment.", "keywords": [ "2019-nCoV", "Address", "Affinity", "Antibodies", "Binding", "Biological Assay", "Biological Markers", "Biomimetics", "Blood", "Blood Tests", "Bluetooth", "Body System", "COVID-19 diagnostic", "Caring", "Cell Separation", "Cell Surface Proteins", "Cell membrane", "Cell surface", "Cells", "Centers for Disease Control and Prevention (U.S.)", "Central Nervous System", "Central Nervous System Infections", "Cerebrospinal Fluid", "Complex", "Detection", "Devices", "Diagnosis", "Diagnostic", "Diagnostic Equipment", "Disease Outbreaks", "Encephalitis", "Engineering", "Equipment", "Eye", "Genitalia", "Glial Fibrillary Acidic Protein", "Glycocalyx", "Glycoproteins", "Goals", "Heparin", "Heparitin Sulfate", "Herpes Simplex Infections", "Herpesviridae Infections", "Herpesvirus 1", "Human", "Human Herpesvirus 2", "Image Analysis", "Individual", "Infection", "Keratitis", "Lateral", "Lesion", "Light", "Link", "Liquid substance", "Membrane", "Meningitis", "Methods", "Mus", "Nervous System Trauma", "Nucleic Acid Amplification Tests", "Paper", "Patient Triage", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Play", "Polysaccharides", "Positioning Attribute", "Printing", "Property", "Proteins", "Proteoglycan", "Publishing", "Rapid diagnostics", "Receptor Cell", "Recommendation", "Recurrence", "Role", "Saliva", "Sampling", "Science", "Serology test", "Serum", "Signal Transduction", "Simplexvirus", "Specificity", "Substance Use Disorder", "Sulfate", "Swab", "Testing", "Time", "Viral Antigens", "Viral Envelope Proteins", "Virulent", "Virus", "Virus Shedding", "World Health Organization", "antigen detection", "antigen test", "cost", "cost effective", "design", "disease transmission", "env Gene Products", "global health", "health care burden", "high risk population", "improved", "infection rate", "innovation", "macromolecule", "nectin", "neurofilament", "novel", "point of care", "point of care testing", "point-of-care detection", "point-of-care diagnosis", "prevent", "quantitative imaging", "rapid test", "screening", "sensor", "success", "test strip", "tool", "transmission process", "viral detection", "viral transmission" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1424, "count": 14236 } } }