Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id" }, "data": [ { "type": "Grant", "id": "15985", "attributes": { "award_id": "1R21AI197441-01", "title": "Sphingolipids and Innate Immunity", "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": 44439, "first_name": "RAJEEV", "last_name": "GAUTAM", "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": 195000, "principal_investigator": { "id": 44440, "first_name": "Fikadu G.", "last_name": "Tafesse", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3435, "ror": "", "name": "OREGON HEALTH & SCIENCE UNIVERSITY", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Type I interferon (IFN) is the first line of defense in innate antiviral immunity, orchestrating transcriptional and metabolic responses that restrict viral replication. While IFN signaling is known to modulate sterol and glycerolipid pathways, its impact on sphingolipids (SPLs)—a class of bioactive lipids involved in immune signaling and cell stress responses—remains poorly understood. Mounting evidence suggests that infections by RNA viruses, including flaviviruses and coronaviruses, induce the accumulation of ceramide (Cer), but whether this promotes viral replication or enhances antiviral defenses is unclear. Our preliminary studies show that Zika virus (ZIKV) triggers overall changes in SPL composition and relies on Cer biosynthesis for successful infection. However, other studies implicate Cer in restricting viral replication and promoting cell survival, raising the possibility that these lipids are upregulated by the host response rather than the virus. The central goal of this proposal is to uncover how type I IFN affects SPL metabolism and to determine whether these lipids, in turn, control the IFN response and infection outcomes. We hypothesize that SPLs, particularly Cer, play a dual role in infection and immunity. Viruses may induce Cer to suppress innate immune responses, including IFN production, as suggested by the known roles of Cer in modulating host signaling pathways. However, we also propose that IFN itself alters SPL metabolism, as it does with other lipid classes, and that these IFN-induced lipid changes may contribute to antiviral defense. To disentangle these possibilities, we will use a combination of untargeted lipidomics, innovative SPL probes, CRISPR gene editing, and organelle-targeted lipid perturbation to systematically determine the causes and consequences of SPL dysregulation in infection. Aim 1 will define how IFN-β alters SPL content and distribution in infected and uninfected cells. In doing so, we will generate the first comprehensive map of IFN-driven changes in the cellular lipidome—including SPLs—across multiple cell types, providing a foundational resource for the broader virology and immunometabolism communities. Aim 2 will determine whether Cer regulates IFN-β signaling and antiviral defense, and whether the subcellular location of Cer influences its role as a pro- or anti-viral signal. Together, these studies will determine how IFN shapes and is shaped by SPLs, providing fundamental insight into the role of these lipids in the earliest steps of antiviral innate immunity.", "keywords": [ "Acceleration", "Affect", "Anabolism", "Anti-viral Agents", "Anti-viral Response", "Autoimmune Diseases", "Cell Survival", "Cell model", "Cells", "Cellular Stress", "Ceramides", "Clustered Regularly Interspaced Short Palindromic Repeats", "Communities", "Coronavirus", "Data", "Disease", "Double-Stranded RNA", "Drug Targeting", "Enzymes", "Family", "Flavivirus", "Genes", "Genetic", "Genetic Transcription", "Goals", "Host Defense", "Host Defense Mechanism", "Immune response", "Immune signaling", "Immunity", "Infection", "Innate Immune Response", "Interferon Type I", "Interferon-β", "Interferons", "Knock-out", "Lipids", "Location", "Malignant Neoplasms", "Maps", "Membrane", "Metabolic", "Metabolic Pathway", "Metabolism", "Natural Immunity", "Organelles", "Outcome", "Pathway interactions", "Play", "Process", "Production", "RNA Virus Infections", "RNA Viruses", "Resources", "Risk", "Role", "Shapes", "Signal Pathway", "Signal Transduction", "Sphingolipids", "Sterols", "Time", "Viral", "Viral Pathogenesis", "Viral Physiology", "Virus", "Virus Diseases", "Virus Replication", "Visual", "Work", "ZIKV infection", "Zika Virus", "antiviral immunity", "biological adaptation to stress", "cell type", "cytokine", "drug repurposing", "global health", "innovation", "insight", "lipid biosynthesis", "lipid metabolism", "lipidome", "lipidomics", "mosquito-borne pathogen", "novel", "pandemic potential", "pharmacologic", "programs", "response", "therapeutic target", "tool", "virology" ], "approved": true } }, { "type": "Grant", "id": "15984", "attributes": { "award_id": "1R01AI195471-01", "title": "Molecular evolution of entry receptor usage underlying zoonotic human betacoronaviruses", "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": "2026-02-20", "end_date": "2031-01-31", "award_amount": 481520, "principal_investigator": { "id": 7514, "first_name": "Tyler Nelson", "last_name": "Starr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 757, "ror": "", "name": "FRED HUTCHINSON CANCER RESEARCH CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3434, "ror": "", "name": "UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH", "address": "", "city": "", "state": "UT", "zip": "", "country": "United States", "approved": true }, "abstract": "Most human viruses originate from recent zoonotic spillover, but the upstream evolutionary processes in animal reservoirs that drive zoonosis-promoting traits remain poorly understood. Our long-term goal is to elucidate the evolutionary forces enabling animal viruses to acquire traits facilitating human spillover and adaptation, with a focus on viral entry receptor usage as a critical determinant of cross-species transmission. Toward this end, this proposal investigates the evolutionary dynamics underlying changes in receptor-binding specificity in beta-coronaviruses (CoVs) linked to past and potential future zoonoses: SARS-CoV-2, MERS- CoV, and HKU1 alongside their bat, rodent, and other animal relatives. Our central model is that long-term evolutionary arms races between viruses and wildlife hosts drive evolvable mechanisms of receptor- engagement promoting subsequent human spillover and adaptation. This model will be examined through three specific aims: (1) Identify mechanisms driving human receptor binding in bat SARS-related CoVs; (2) Dissect the origins and consequences of receptor-switching in bat MERS-related CoVs; and (3) Identify evolutionary origins of and functional constraints imposed by a newly discovered HKU1 CoV receptor. In each aim, we combine phylogenetic surveys across diverse animal CoVs with high-throughput mutagenesis screens to map the evolutionary, genetic, and structural mechanisms driving receptor-use transitions and their downstream evolutionary consequences. These studies will illuminate how host-virus dynamics shape receptor-binding architectures to enable zoonotic potential and post-spillover antigenic evolution. The resulting large-scale genotype-phenotype maps will inform computational models for assessing viral zoonotic risk and guide the design of broad-spectrum antibody and vaccine therapeutics for pandemic preparedness. Taken together, this work advances understanding of mechanisms of viral evolution while providing actionable insights for proactive ecological, diagnostic, and therapeutic interventions.", "keywords": [ "2019-nCoV", "ACE2", "Animals", "Antibodies", "Architecture", "Automobile Driving", "Binding", "Biological Factors", "Chiroptera", "Communicable Diseases", "Computer Models", "Coronavirus", "Development", "Diagnostic", "Dissection", "Distal", "Epidemic", "Event", "Evolution", "Future", "Genetic", "Genetic Screening", "Genotype", "Glycoproteins", "Goals", "Human", "Immune", "Infection", "Link", "Maps", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Molecular", "Molecular Evolution", "Mutagenesis", "Mutation", "Orthologous Gene", "Pathogenicity", "Pathway interactions", "Phenotype", "Phylogenetic Analysis", "Process", "Proteins", "Public Health", "Research", "Risk", "Rodent", "Role", "SARS coronavirus", "Shapes", "Specificity", "Surveys", "TMPRSS2 gene", "Testing", "Therapeutic", "Therapeutic Intervention", "Vaccines", "Viral", "Viral reservoir", "Virus", "Work", "Yeasts", "Zoonoses", "animal coronavirus", "arms race", "betacoronavirus", "biophysical analysis", "coronavirus receptor", "cross-species transmission", "design", "experience", "future pandemic", "human coronavirus", "improved", "insight", "mutation screening", "novel", "pandemic preparedness", "predictive tools", "pressure", "prevent", "receptor", "receptor binding", "respiratory", "tool", "trait", "transmission process", "vaccine development", "viral outbreak", "zoonotic spillover" ], "approved": true } }, { "type": "Grant", "id": "15983", "attributes": { "award_id": "1R35GM162443-01", "title": "Molecular Mechanisms of Antimicrobial Resistance from Machine Learning Augmented Enhanced Sampling", "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": 44257, "first_name": "ANNE", "last_name": "GERSHENSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-24", "end_date": "2030-12-31", "award_amount": 401285, "principal_investigator": { "id": 44438, "first_name": "Dhiman", "last_name": "Ray", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3433, "ror": "", "name": "UNIVERSITY OF OREGON", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT: Antimicrobial resistance threatens our ability to treat previously curable infectious diseases and may soon become a global public health crisis. The Ray group aims to understand and characterize the molecular mechanisms of antibiotic and antiviral resistance to identify potential avenues to target resistant pathogens. This R35 MIRA pro- gram involves two distinct research projects that utilize advanced machine learning (ML) and enhanced sampling algorithms for molecular dynamics (MD) simulations to gain mechanistic insights into antimicrobial resistance and facilitate the development of future therapeutic applications. In the first project, we will study the process of ligand binding to riboswitches, a class of regulatory RNA segments that are potential targets for next-generation antibi- otics. Our goal is to identify the role of conformational dynamics and distant nucleotide mutations in modulating the binding mechanism of the small molecule inhibitors (e.g., Ribocil) to RNA targets (e.g., Flavin-mononucleotide (FMN) riboswitch). We will design neural network (NN) and explainable artificial intelligence (XAI) based collec- tive variables from system agnostic descriptor space and perform enhanced sampling simulations to compute the free energy landscape of riboswitch conformational transition and ligand binding. This work will provide key mechanistic insights into RNA-small-molecule interactions and pave the way for designing more resilient antibi- otics. In the second project, we will study how resistant mutations in the viral antigens, e.g., SARS-CoV-2 spike protein, affect the binding mechanism of neutralizing antibodies. Previous research in this area primarily focused on the antigen-antibody interface but often overlooked the long-range allosteric effect of antigen mutations on the antibody binding process. We will perform NN and XAI-guided enhanced sampling simulations to elucidate the mechanistic details of antigen-antibody recognition. In addition, we will trace the allosteric communication path- ways using mutual-information-based protein graph connectivity networks constructed for various intermediate configurations sampled from the association pathway. This work will open new avenues for the rational design of broad-spectrum monoclonal antibodies through the judicious strengthening of distant regions of the antibody structure that are less susceptible to epitope mutations.", "keywords": [ "Affect", "Algorithms", "Antibiotics", "Antibodies", "Antigens", "Antimicrobial Resistance", "Area", "Bacterial RNA", "Binding", "Communicable Diseases", "Communication", "Computer Simulation", "Descriptor", "Development", "Distant", "Epitopes", "Flavin Mononucleotide", "Free Energy", "Future", "Goals", "Graph", "Ligand Binding", "Machine Learning", "Molecular", "Molecular Conformation", "Monoclonal Antibodies", "Mutation", "Nucleotides", "Pathway interactions", "Pharmaceutical Preparations", "Predisposition", "Process", "Proteins", "Public Health", "RNA", "Research", "Research Project Grants", "Resistance", "Resistance development", "Role", "SARS-CoV-2 spike protein", "Sampling", "Small RNA", "Structure", "System", "Therapeutic", "Viral Antigens", "Viral Drug Resistance", "Viral Proteins", "Work", "conformational conversion", "design", "drug candidate", "explainable artificial intelligence", "future antibiotics", "insight", "molecular dynamics", "neural network", "neutralizing antibody", "novel therapeutic intervention", "pathogen", "programs", "rational design", "resilience", "resistance mutation", "simulation", "small molecule", "small molecule inhibitor" ], "approved": true } }, { "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": "15981", "attributes": { "award_id": "1R21AI190798-01A1", "title": "Detection of Shigella Species in Wastewater - A Pilot Study for Community and Building Scale Wastewater-Based Surveillance of Bacterial Pathogens", "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": "2026-02-03", "end_date": "2028-01-31", "award_amount": 422125, "principal_investigator": { "id": 44436, "first_name": "Anthony T", "last_name": "Maurelli", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3432, "ror": "", "name": "UNIVERSITY OF FLORIDA", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Bacillary dysentery or shigellosis is caused by bacteria of the Shigella species: S. dysenteriae, S. flexneri, S boydii, and S. sonnei. Infections range from mild or asymptomatic to severe bloody diarrhea, so reported prevalence grossly underestimates actual prevalence. Shigellosis is a global public health concern and antimicrobial resistance has compounded the problem. Moreover, shigellosis is also sexually transmitted in the United States, Europe, and other developed countries. Such outbreaks are driven by the emergence of antibiotic resistant strains of S. flexneri infecting men who have sex with men. The objective of this proof-of-concept study is to demonstrate that wastewater-based epidemiology (WBE) using digital PCR to detect pathogen molecular markers can provide a more accurate picture of community prevalence of bacterial pathogens than traditional case reporting. Wastewater surveillance for viral pathogens has been in use for decades and its use to monitor SARS-CoV-2 is now widely applied globally. Analogous methods for wastewater surveillance of bacterial pathogens by digital PCR has lagged. We will develop and validate methods to detect Shigella, an important bacterial agent of diarrheal disease, in wastewater. We will also field test the methods to assess shigellosis prevalence at community and building scale and link the data to the actual population residing in the wastewater collection area. We will provide actionable data to the local health department which can then develop targeted public health interventions. The independent but complementary aims in demonstrating the proof-of-concept are: 1. Develop and validate sensitive, specific, and reproducible WBE methods for detection of Shigella species in wastewater using digital PCR. Three subaims will: 1.1) optimize methods for extraction and detection of Shigella in wastewater using laboratory-grown strains of Shigella species to “spike” authentic wastewater and laboratory prepared “synthetic” wastewater; 1.2) validate molecular targets for differentiation of S. flexneri from S. sonnei in wastewater; and 1.3) culture of Shigella from wastewater to assess antibiotic resistance genotypes and phenotypes. 2. Assess proof-of-concept of WBE as a public health tool for Shigella at community and building scale with emphasis on high risk congregate populations, i.e., day care centers. Two subaims will: 2.1) measure the prevalence of Shigella species at community scale by sampling at the wastewater treatment plant intake and using wastewater flow rate as a population normalization marker; and 2.2) extend shigellosis surveillance to building scale targeting high risk congregate pediatric populations. Strengths of this proposal are the innovative application of WBE to a bacterial pathogen, our method for population normalization, differentiation of Shigella species, prevalence measurement of Shigella species at community and building scale, and the expertise of our multidisciplinary team.", "keywords": [ "2019-nCoV", "Antibiotic Resistance", "Antimicrobial Resistance", "Area", "Automobile Driving", "Bacteria", "Bacterial Infections", "Behavior", "COVID-19 monitoring", "COVID-19 surveillance", "Case Study", "Centers for Disease Control and Prevention (U.S.)", "Childhood", "Collection", "Communities", "County", "Data", "Day center care", "Detection", "Developed Countries", "Development", "Disease", "Disease Outbreaks", "Dysentery", "Effectiveness", "Europe", "Excretory function", "Feces", "Florida", "Foundations", "Future", "Genetic", "Genotype", "Health", "Health Resources", "Hemorrhagic colitis", "Hot Spot", "Individual", "Infection", "Intake", "Intervention", "Laboratories", "Link", "Measles", "Measurement", "Measures", "Methodology", "Methods", "Molecular", "Molecular Analysis", "Molecular Profiling", "Molecular Target", "Monitor", "Pathogen detection", "Patients", "Phenotype", "Pilot Projects", "Plants", "Poliomyelitis", "Population", "Population Surveillance", "Populations at Risk", "Prevalence", "Public Health", "Reporting", "Reproducibility", "Research Proposals", "Sampling", "Sexual Transmission", "Shigella", "Shigella Infections", "Shigella boydii", "Shigella dysenteriae", "Shigella flexneri", "Shigella sonnei", "System", "Techniques", "Testing", "United States", "Universities", "Variant", "Viral", "Work", "detection method", "diarrheal disease", "digital", "experience", "field study", "global health", "high risk", "innovation", "men who have sex with men", "molecular marker", "multidisciplinary", "novel", "pathogenic bacteria", "pathogenic virus", "public health intervention", "resistant strain", "tool", "wastewater epidemiology", "wastewater monitoring", "wastewater samples", "wastewater sampling", "wastewater surveillance" ], "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": "15979", "attributes": { "award_id": "1R21AI188074-01A1", "title": "Identification of RNAi-independent antiviral genes through biased genetic screen in C. elegans", "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": 32860, "first_name": "KENTNER L", "last_name": "SINGLETON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-02", "end_date": "2028-01-31", "award_amount": 412500, "principal_investigator": { "id": 44434, "first_name": "Rui", "last_name": "Lu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3430, "ror": "", "name": "LOUISIANA STATE UNIV A&M COL BATON ROUGE", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses, especially RNA viruses, are formidable pathogens to cellular hosts. Owing to the error-prone nature of their replicases, RNA viruses rapidly accumulate large numbers of genetic mutations in their genome, enabling them to evade immune detection. Some RNA viruses, such as influenza viruses and coronaviruses, can also generate genome variants through genome reassortment or genome recombination mechanisms. It is thus important to study antiviral mechanisms intrinsically resistant to genetic mutations in viral genome, which may lead to the development of novel antiviral strategies. In plants, insects and vertebrates, there are antiviral mechanisms triggered by non-dsRNA products of invading viruses. These antiviral mechanisms provide another layer of protection in case viral dsRNA-triggered immunity is compromised by the invading viruses. In supporting this hypothesis, many plant and animal viruses have been found to produce diverse types of dsRNA binding proteins that are able to bind and sequester viral dsRNA to block immune detection. So far, RNAi is known as the most important antiviral defense mechanism in Caenorhabditis elegans. However, some recent studies on worm antiviral defense suggest that viral infection in C. elegans triggers transcriptional programs that in return provide protection against invading viruses in an RNAi-independent manner. Therefore, very much like what has been demonstrated in plants and insects, RNAi-independent antiviral defense (RiAD) may provide worms another layer of protection against virus in case antiviral RNAi is compromised. To fill the knowledge gap in our understanding of worm RiAD and as proof of principle, the PI’s lab has recently carried out a biased genetic screen of limited scale, aiming to identify genes specifically contributing to worm RiAD. This genetic screen identified 8 candidate genes that confer RiAD targeting a flock house virus (FHV) replicon. 5 of these candidate genes also mediate RiAD against Orsay virus, which naturally infects C. elegans (21). In this application, we propose to continue the biased genetic screen and finish it on a much greater scale to ensure double coverage on all genes involved in RiAD. We will then map and identify the candidate genes through whole genome sequencing combined with feeding RNAi and function rescue assay. Since approximately 70% of C. elegans genes have human homologs, function and mechanism study of the identified genes may not only lead to the identification of novel conserved mechanisms of antiviral innate immunity across kingdoms but also inform the development of novel antiviral strategies.", "keywords": [ "Alleles", "Animals", "Anti-viral Agents", "Anti-viral Response", "Binding", "Binding Proteins", "Biological Assay", "Caenorhabditis elegans", "Candidate Disease Gene", "Complement", "Coronavirus", "Defense Mechanisms", "Detection", "Development", "Double-Stranded RNA", "Ensure", "Genes", "Genetic", "Genetic Recombination", "Genetic Screening", "Genetic Transcription", "Genome", "Homologous Gene", "Human", "Immune", "Immune Evasion", "Immunity", "Insecta", "Interferons", "Invaded", "Knowledge", "Lead", "Mammals", "Maps", "Mediating", "Mutation", "Natural Immunity", "Nature", "Nematoda", "Organism", "Pathway interactions", "Plants", "RNA Interference", "RNA Viruses", "Replicon", "Research", "Resistance", "Variant", "Vertebrates", "Viral", "Viral Genes", "Viral Genome", "Virus", "Virus Diseases", "Work", "antiviral immunity", "candidate identification", "design", "feeding", "gene function", "genome sequencing", "genome-wide", "influenzavirus", "novel", "pathogen", "pathogenic virus", "programs", "protective pathway", "replicase", "response", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15978", "attributes": { "award_id": "1R01AI196176-01", "title": "Inhibiting Chikungunya Virus Protease using MTase-like Domain Interactions for Novel Antiviral Therapies.", "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": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-23", "end_date": "2031-01-31", "award_amount": 632994, "principal_investigator": { "id": 44433, "first_name": "Jeanne Ann", "last_name": "Hardy", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3429, "ror": "", "name": "UNIVERSITY OF MASSACHUSETTS AMHERST", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Chikungunya (CHIKV) is an RNA alphavirus that infects 3 million people in 45 countries including the US annually. Acute infection is flu-like, but in 40% of infections, debilitating joint pain emerges that can last for years. Infection during pregnancy also results in severe encephalopathy in newborns or aborted fetuses. Viral proteases are effective antiviral drug targets and are the standard of care for viral diseases (e.g HIV, hepatitis C, SARS-CoV- 2). The activity of the nsP2 protease from CHIKV (CHIKVP) is vital for infection. Inhibition of CHIKVP blocks processing of the viral polyprotein, prevents viral replication, lowers viral titers and stops disease progression. Thus, CHIKVP is an excellent antiviral drug target. To date, no effective antivirals of CHIKVP have been approved for acute or chronic infection. Our ultimate goal is to use insights into CHIKVP structure and dynamics to develop an inhibitor to oppose CHIKV infection, the resulting chronic pain and prevent pediatric neurological syndromes. CHIKVP is composed of a protease domain and a methyltransferase-like domain (MTL). To date, no functions of the MTL have been identified. In a search for novel CHIKVP binders, we identified ligands that bind to the MTL at an elongated cavity and allosterically inactivate the protease. The site shares structural homology with S-adenosyl methionine (SAM) cofactor binding sites, but does not bind SAM. The allosteric site binds to GTP, which suggests that a function such as RNA binding may be conserved in the MTL. Here we propose a research strategy for the development and direct comparison of CHIKVP active-site and allosteric inhibitors. We will build compounds derived from a large compound screen and also build from MTL-binding fragments we have already identified. We have developed NMR approaches that allow us to readily distinguish active-site from allosteric inhibitors. Importantly, we have developed approaches that allow us to monitor activity, binding and dynamics in solution without having to rely on freezing samples which is required for other structural techniques, to inform our inhibitor design. Recent data have suggested that RNA plays a critical role in CHIKVP function, enhancing protease activity. We have identified a site that we hypothesize binds RNA and describe a series of studies to understand the mechanism by which RNA impacts protease function. We will bring all these structural insights into our inhibitor development approach. At each step of development, we will closely monitor efficacy against viral infection for CHIKV and other related alphaviruses to determine whether pan-alphaviral inhibition is achievable with a given class of compounds. Critically, we will also implement a directed evolution approach across both domains of CHIKVP to predict the susceptibility of our inhibitors to resistance mutations. This will enable us to develop enduring antivirals and will also address longstanding unanswered questions about the favorability of allosteric inhibition in antiviral drug development.", "keywords": [ "2019-nCoV", "Aborted Fetus", "Active Sites", "Address", "Adult", "Allosteric Site", "Alpha Virus", "Anti-viral Agents", "Anti-viral Therapy", "Arthralgia", "Back", "Binding", "Binding Sites", "Characteristics", "Chikungunya virus", "Child", "Childhood", "Clinical", "Country", "Data", "Development", "Directed Molecular Evolution", "Disease", "Disease Progression", "Drug Targeting", "Drug resistance", "Encephalopathies", "FDA approved", "Family", "Fluorogenic Substrate", "Freezing", "Future", "Goals", "Guanosine Triphosphate", "HIV", "HIV Care", "Hepatitis C", "Hepatitis C virus", "Infection", "Inflammation", "Intervention", "Late pregnancy", "Ligand Binding", "Light", "Mediating", "Methyltransferase", "Molecular", "Monitor", "Motion", "Myalgia", "Nervous System Disorder", "Neurologic", "Newborn Infant", "Peptide Hydrolases", "Persons", "Pharmaceutical Chemistry", "Play", "Polyproteins", "Predisposition", "Pregnancy", "Pregnant Women", "Property", "Protease Domain", "Protease Inhibitor", "RNA", "RNA Binding", "Reporting", "Research", "Role", "S-Adenosylhomocysteine", "S-Adenosylmethionine", "SARS-CoV-2 infection", "Sampling", "Series", "Site", "Structure", "Syndrome", "Techniques", "Testing", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Virus Inhibitors", "Virus Replication", "acute infection", "antiviral drug development", "chikungunya infection", "chronic infection", "chronic pain", "cofactor", "design", "drug resistance development", "emerging pathogen", "enzyme mechanism", "flu", "high throughput screening", "inhibitor", "insight", "mosquito-borne", "novel", "pain symptom", "pandemic potential", "pandemic virus", "pharmacologic", "prevent", "resistance mutation", "screening", "small molecule", "standard of care", "unborn child" ], "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 } }, { "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 } } ], "meta": { "pagination": { "page": 2, "pages": 1424, "count": 14236 } } }