DR69 DataRelease
Release Date: October 2026
New Studies: 11
Updated Studies: 15
New Studies
| SDY2734: Novel method reveals unique immune signatures in blood T cell-monocyte complexes during infection | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | We developed a novel method to study the transcriptome and adaptive immune receptor repertoire of single cells forming complexes in a high-throughput fashion, without the need for bioinformatic deconvolution. | ||||||||||||||||||
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| DOI: | 10.21430/M3YCYH1D99 | ||||||||||||||||||
| Subjects: | 20 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
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| SDY3096: Systems Immunolobiology of Antibiotic-Persistent MRSA Infection | |||||||
| Status: | New | ||||||
| Description: | Staphylococcus aureus bacteremia (SAB) is a common and life-threatening bloodstream infection that is often caused by methicillin-resistant strains (MRSA). Of urgent concern, up to 30% of SAB patients fail antibiotic treatment even when gold-standard anti-MRSA therapy (vancomycin [VAN] or daptomycin (DAP]) is used. These patients have persistent bacteremia, which frequently results in a dismal clinical outcome. Even though the MRSA isolates from these patients appear to be susceptible to VAN or DAP based upon in vitro CLSI breakpoints, these antibiotics fail to clear the bloodstream infection. Such in vivo antibiotic resistance is termed Antibiotic-Persistent MRSA Bacteremia, or APMB. At present, there are few therapeutic options for these life-threatening infections. There is a critical, unmet need to understand the unique intersection of host and pathogen factors driving APMB. Elucidating these factors holds promise to lead to new approaches to prospectively identify patients at risk for developing APMB, and novel strategies to prevent or treat this often devastating infection. Importantly, APMB represents a unique subset of antibiotic resistant infections that differ from biofilm-associated infections due to antibiotic-tolerant or recalcitrant / relapsing isolates. APMB isolates are genetically stable, but highly adaptive strains induced by in vivo antibiotic exposure. Thus, mechanisms of persistent infections (APMB) are distinct from antibiotic-tolerant infections. Based on our extensive preliminary data, we hypothesize that APMB results from a three-way interaction among the pathogen, host immune response and antibiotic. We further posit that conventional approaches to study this clinically important phenomenon may be insufficient to understand it. Therefore, we will: 1) analyze the interactions of wild-type and mutant APMB strains with host cells and constituents in vitro, ex vivo, and in discriminative animal models to resolve key genotypic & phenotypic determinants of the S. aureus persistome that drives APMB; 2) leverage our pioneering S. aureus Bacteremia Group (SABG) biorepository of human samples & matched clinical isolates, genomic & transcriptional analysis, and immunophenotyping to define host genetic and immune profiles of APMB during VAN or DAP treatment; and 3) use our powerful systems-based statistical and computational immunology approaches to integrate results of high-throughput genomics and transcriptomics data across studies to model the pathogen-host signatures unique to APMB. Therefore, we will resolve the pathogen and host factors that drive APMB to enable innovative approaches to predict, prevent and treat MRSA bloodstream infections that persist despite antibiotic treatment. These critically needed advances will derive from iterative refinement of studies that bring together proven strengths of an outstanding research team to apply an integrated, systems-based approach. The result will yield robust predictive algorithms for clinical evaluation for improved interventions against MRSA infections. | ||||||
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| DOI: | 10.21430/M3SRUA8OPN | ||||||
| Subjects: | 148 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3145: HLA class I downmodulation in MPNs | ||||||||||
| Status: | New | |||||||||
| Description: | Somatic mutations of the calreticulin (CRT) gene (CALR) are one group of driver mutations in myeloproliferative neoplasms (MPNs). CRT is important for the assembly of human leukocyte antigen (HLA) class I molecules. Typically, CALR mutations in MPN occur in a heterozygous context, with the retention of one wild-type CALR allele. We find that heterozygous knock-in of MPN-linked CALR mutation in human cell lines maintains or slightly induces surface HLA class I expression in an allele-specific manner. In contrast to the haploinsufficiency condition, full deficiency of wild-type CRT negatively affects surface HLA class I expression in an allele-specific manner, and MPN-associated CRT mutants fail to restore expression for all tested allotypes. Consistent with the heterozygous nature of CALR mutations in MPN, surface HLA class I expression in platelets and monocytes from MPN patients with CALR mutations generally falls within the normal range, with higher expression measured in monocytes from essential thrombocythemia (ET) patients treated with interferon alpha. Overall, the studies indicate small effects of wild-type CRT haploinsufficiency on surface HLA class I expression, which is of relevance to the majority of MPN patients with CALR mutations. Additionally, the loss of HLA class I expression in cells fully deficient in wild-type CRT is allele-dependent and correlates with previously reported effects of the HLA class I assembly factor tapasin. | |||||||||
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| DOI: | 10.21430/M3UFB6KPNL | |||||||||
| Subjects: | 0 | |||||||||
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| Publications: | None | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
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| SDY3464: Synovial Fluid Immune Cell Landscape In Juvenile Idiopathic Arthritis | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Juvenile idiopathic arthritis (JIA) is a common inflammatory rheumatic disease of childhood, yet the mechanisms driving immune activation in affected joints remain unclear. In this study, we analyzed synovial fluid (SF) immune cells from patients with JIA using two complementary methodologies, single-cell multiomics and flow cytometry. This comprehensive characterization of the SF immune environment provides a foundation for future studies aimed at defining the roles of specific immune cell subsets in JIA pathogenesis. | ||||||||||||
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| DOI: | 10.21430/M374MZPGJR | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
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| SDY3490: 35th Multicenter Airway Research Collaboration (MARC-35): airway metagenome endotyping at age 6 years | |||||||||||||
| Status: | New | ||||||||||||
| Description: | In a multicenter prospective cohort study of infants (age <1 year) hospitalized for bronchiolitis, we sought to identify airway metagenome endotypes at age 6 years that are associated with childhood asthma. From nasal swab samples collected at the 6-year follow-up visit, we extracted total genomic DNA and constructed libraries. Metagenomic shotgun sequencing of library pools was performed on the Illumina NovaSeq6000 platform (San Diego, USA), using paired-end chemistries with the read length of 2x150b. We conducted taxonomy profiling using MetaPhlAn3 and functional profiling of the microbial community using HUMAnN3. We plan to use the network fusion clustering approach to help identify distinct metagenome-host genome endotypes and examine their association with asthma by age six years. Results are pending. | ||||||||||||
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| DOI: | 10.21430/M31ZW1MVG7 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
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| SDY3677: Molecular and Functional Analysis of Calcium Binding by a Cancer-linked Calreticulin Mutant | ||||||||||
| Status: | New | |||||||||
| Description: | Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone with low affinity calcium binding sites in its C-terminal domain. This region is altered by somatic mutations in the CRT gene (CALR), which drive a subset of myeloproliferative neoplasms (MPN). Perturbations in ER calcium storage and signaling are reported for the MPN type I mutant, CRTDel52, and are linked to disease pathogenesis. Using recombinant CRT proteins, we found similar low affinity calcium binding characteristics for wild-type CRT and CRTDel52, as determined by isothermal titration calorimetry (ITC). Residues 340–349, conserved in both wild-type CRT and CRTDel52, contribute to binding. Furthermore, ER and cytosolic calcium levels and store-operated calcium entry (SOCE) were comparable in CRT knockout (CRT-KO) cells reconstituted with wild-type CRT or CRTDel52. Notably, the CRT-KO induces expression of multiple ER proteins known to contain low affinity calcium binding sites or regulate ER calcium levels. Overall, these findings indicate that CRTDel52 retains at least some low affinity calcium binding capacity and that CRT-deficiency induces compensatory cellular changes that maintain ER calcium homeostasis. | |||||||||
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| DOI: | 10.21430/M3IQGOHZUZ | |||||||||
| Subjects: | 0 | |||||||||
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| Publications: | None | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
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| SDY3710: Impact of cbVGs in circadian genes | |||||||
| Status: | New | ||||||
| Description: | The circadian clock regulates fundamental cellular processes that include the host response to infection. However, the intersection of the circadian clock and the mechanisms that drive antiviral immunity remains poorly understood. Copy-back viral genomes (cbVGs) generated during virus replication strongly stimulate immunity during infection with negative-sense RNA viruses. Here, we demonstrate at the single cell level that A549 lung epithelial cells, commonly used to model lung infections, sustain circadian rhythms and upon infection with Sendai virus (SeV) progressively remodel the circadian clock through an innate immune response driven primarily by cbVGs. Furthermore, we show that cbVG-driven changes in circadian gene expression are mediated through two distinct innate immune sensing pathways: the RIG-I adaptor MAVS is required for preferential induction of the BMAL1 paralog ARNTL2, whereas the double-stranded RNA sensor PKR is required for the cbVG-specific induction of the negative-feedback regulators NR1D1, NR1D2, and PER1. A similar cbVG-specific signature was observed during respiratory syncytial virus infection, suggesting that cbVG-driven circadian gene regulation is not unique to SeV. In addition, we established through gain- and loss-of-function experiments that ARNTL2 is functionally required for amplifying the transcriptional response to infection, with selective effects on the expression of specific antiviral genes, including CCL5. Together, these findings establish innate immune signaling triggered by cbVGs as selective driver of circadian clock gene expression during viral infection through distinct sensing pathways and identify ARNTL2 as a previously unrecognized regulator of virus-induced host transcriptional responses. | ||||||
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| DOI: | 10.21430/M33DCX3CX6 | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3736: BCG induces immunometabolic shifts in vitro and in vivo: Implications for neonatal trained immunity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | BCG vaccine protects infants against disseminated tuberculosis (TB), but also against unrelated infections via incompletely understood mechanisms, including metabolic reprogramming of innate immune cells._Applying global metabolomics to a human in vitro monocyte (Mo) training (MOTRA) platform, we identified metabolites significantly perturbed after primary BCG stimulation (Day 1) and BCG training (Day 7) in newborn and adult Mo culture supernatants. Findings were validated within an in vivo cohort, suggesting relevance and robustness of the in vitro model and distinct signatures of BCG primary and trained immunity in newborns. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3XCCP39HV | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 22 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Publications: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY3807: Multi-omic profiling defines subtype-specific extracellular vesicle signatures in early human pregnancy | |||||||
| Status: | New | ||||||
| Description: | Early human pregnancy (11-15 weeks) is a critical period when placental dysfunction begins but remains clinically undetectable, preventing early intervention for pregnancy complications. This highlights a pressing need for circulating biomarkers that can signal the onset of a complication. Circulating extracellular vesicles (EVs) carry bioactive cargo that reflect originating cell activity in real-time, positioning them as early biomarkers of pregnancy complications. While pregnancy studies have identified plasma EV cargo alterations across complications, studying small EVs alone—the field standard—or bulk EVs together obscures pathological changes that may manifest preferentially in one population. To address this, we performed the first multi-omic comparison of small and large EVs from healthy pregnancies at 11-15 weeks (n=10) to establish subtype-specific cargo differences and provide a reference for detecting pathological alterations. We quantified mitochondrial DNA (mtDNA), performed transcriptomics (mRNAs, miRNAs) and proteomics to define small and large EV signatures. Large EVs were preferentially enriched for mitochondrial cargo including DNA, transcripts, and proteins as well as transcripts and proteins relating to hypoxia response, endocrine signaling, and VEGF signaling. In contrast, small EVs were enriched for canonical EV and basement membrane proteins. Additionally, using small RNA-seq we found that EV miRNA composition was similar across subtypes despite their known functional roles as biomarkers of various pathologies. These distinct large and small EV cargo signatures underscore the importance of profiling both populations for biomarker discovery. Together these data provide a baseline for future studies linking EV signature alterations to placental dysfunction and adverse pregnancy outcomes. | ||||||
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| DOI: | 10.21430/M3LWPL0K15 | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY3814: Enhancing, controlling, and sterilizing dengue immunity and the development of broadly protective responses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Dengue is the canonical viral disease for which immune history predicts protective versus pathogenic responses and immunogenicity. Yet, due to limitations in animal models and clinical presentation after peak viremia, how pre-infection and early immune responses affect dengue outcomes is not confirmed. We conducted a phase 1 clinical trial with 45 healthy adults to test if secondary infection challenge with a heterotypic, full-length, attenuated virus increases viremia and immunogenicity compared to primary and tertiary infection. Viremia was associated with more, but still mild, clinical signs and symptoms, and secondary infection predicted greater viremia and neutralizing antibodies. However, those with the highest baseline enhancing antibodies experienced delayed inflammatory and adaptive activation, the highest viremia, strong acute immune responses, but waning of potent CD8+ T cells and antibodies. Baseline antibodies to non-structural protein 1 of multiple serotypes predicted early interferon and balanced immune activation, viremia control, and development of enduring, potent B and T cells, revealing how vaccines can induce broad long-lasting protection. Finally, these antibody and T cell profiles at baseline predicted sterilization of infection. We demonstrate that controlled human challenge can delineate coordinated versus dysregulated acute responses and effects on immunogenicity, informing therapeutic and vaccine strategies for dengue and other viral diseases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M36OQ4LYDQ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Publications: | None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Assays: | None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Assessments: | None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY3815: Live-Attenuated Rift Valley Fever Virus Vaccination Leads to Durable, Protective Immunity Independent of Sex in C57BL/6 Mice | ||||||||||
| Status: | New | |||||||||
| Description: | Background. Rift Valley fever virus (RVFV) is a zoonotic arbovirus endemic to Africa and the Arabian Peninsula that can cause disease in humans and livestock. There are currently no licensed vaccines for human use, but several candidates are at the clinical trial, stage including DDVax™, a preparation of live-attenuated RVFV lacking the nonstructural proteins NSs and NSm (ΔNSsΔNSm). Multiple preclinical studies have shown that ΔNSsΔNSm is safe and immunogenic. Methods. The longitudinal study described in this manuscript examined the additional features of duration, sex, and dose in immunogenicity and protection provided by ΔNSsΔNSm. Female and male 8-week-old C57BL/6 mice were vaccinated with either a low or high dose of ΔNSsΔNSm and humoral (via neutralization assay and enzyme-linked immunosorbent assay) and cellular immunity (enzyme-linked immunospot and flow cytometry) were assessed over a period of 6 months. A subset of animals was challenged with a lethal dose of wild-type RVFV 6 months postvaccination. Results. All vaccinated animals were protected against lethal RVF disease 6 months postvaccination independent of dose or sex. Humoral immunity in the form of RVFV-specific neutralizing and binding antibodies decreased over time but remained detectable at the end of the study. The RVFV-specific CD4+ T cells also decreased by 6 months postvaccination. In contrast, virus-specific polyfunctional CD8+ T cells persisted at comparable levels throughout the study. Conclusions. This work demonstrates that a single low-dose ΔNSsΔNSm vaccine elicits a durable humoral and cellular immune response that persists over months and protects C57BL/6 mice against lethal RVF disease. | |||||||||
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| DOI: | 10.21430/M3I9EGP7V5 | |||||||||
| Subjects: | 0 | |||||||||
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Updated Studies
| SDY620: Atopic Dermatitis Research Network (ADRN) Influenza Vaccine Study (ADRN-05) | |||||||||
| Status: | Updated | ||||||||
| Description: | This is a multi-site, randomized, open label, mechanistic study designed to compare the immune response in non-atopic and AD participants receiving a single dose of the 2012-2013 seasonal Fluzone Intradermal vaccine administered per label. A secondary objective is to compare the immune response of AD participants receiving intradermal influenza vaccination to the response of AD participants receiving intramuscular influenza vaccination. | ||||||||
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| DOI: | 10.21430/M3UT5M218G | ||||||||
| Subjects: | 368 | ||||||||
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| SDY1027: The Role of Epigenetics in Inner City Asthma (ICAC-15) | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | The study is designed to determine the relation between methylation of CpG motifs and asthma in children residing in the inner city. | ||||||||||||||||||
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| DOI: | 10.21430/M3SXDBHQTS | ||||||||||||||||||
| Subjects: | 200 | ||||||||||||||||||
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| SDY1433: Optimization of NULOJIX (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15) | ||||||||||||||||||
| Status: | Updated | |||||||||||||||||
| Description: | Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term. | |||||||||||||||||
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| DOI: | 10.21430/M3CEH2A7ZF | |||||||||||||||||
| Subjects: | 44 | |||||||||||||||||
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| SDY1515: Peanut Sublingual Immunotherapy (CoFAR4) | |||||||||||||||||
| Status: | Updated | ||||||||||||||||
| Description: | Peanut allergy is a common ailment in the United States. Research suggests that the prevalence of peanut allergy in the United States has doubled over the last 5 years. Currently, the only effective treatment for peanut allergy is a peanut-free diet and quick access to self-injectable epinephrine in the event of peanut exposure. The sublingual route is a potential method to administer immunotherapy for the treatment of food allergies. The intent of this study is to induce desensitization and eventually tolerance to peanut protein and evaluate the safety and immunologic effects of daily sublingual immunotherapy (SLIT) for individuals with peanut allergy. The trial will enroll 40 participants. After the first 10 participants between the ages of 18 and 40 are enrolled, safety information will be reviewed. If there are no safety concerns, the study will continue to enroll the remaining participants between the ages of 12 and 40. This clinical trial will last 172 to 216 weeks. Participants will be randomly assigned to receive peanut SLIT or placebo SLIT. All participants will have an entry oral food challenge (OFC). The treatment group will receive gradual dosing escalations of peanut SLIT and maintenance therapy over a 44-week period, followed by another OFC. Following the OFC, participants will be unblinded, and the placebo group will receive peanut SLIT escalated to a higher maximum dose than the first treatment group. Maintenance therapy will continue for both groups for more than 2 years. Study visits will occur every 2 weeks during dosing escalations of peanut SLIT, followed by visits gradually spacing out during maintenance to every 12 weeks. At selected visits, a physical examination, skin prick tests, blood and urine collection, and atopic dermatitis and asthma evaluations will occur. Approximately 6 OFCs will be administered to each participant throughout the course of the study. Additionally, 10 participants will be enrolled as control participants who will not receive any study therapy and will only have blood drawn at 3 visits throughout the course of the trial. | ||||||||||||||||
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| DOI: | 10.21430/M3UH9QGIY2 | ||||||||||||||||
| Subjects: | 62 | ||||||||||||||||
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| Assays: | None | ||||||||||||||||
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| SDY1519: Eosinophilic Esophagitis Databank (CoFAR5) | ||||||||||||||
| Status: | Updated | |||||||||||||
| Description: | This is a multi-site, single visit registry in subjects aged 6 months to 65 years old, of any race, gender, or ethnicity with a biopsy confirmed EoE. Participants/parents/guardians will provide responses regarding the medical history, and will provide salivary and/or blood samples. The study team will have access to the participant's medical record to verify diagnosis information and medical history. | |||||||||||||
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| DOI: | 10.21430/M36BWCCNH7 | |||||||||||||
| Subjects: | 709 | |||||||||||||
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| Assays: | None | |||||||||||||
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| SDY1520: Peanut Epicutaneous Immunotherapy (CoFAR6) | |||||||||||||||
| Status: | Updated | ||||||||||||||
| Description: | This is a multi-center, randomized, double-blind, placebo-controlled trial of DBV712 (Viaskin Peanut) in peanut-allergic subjects reacting to <1044 mg of peanut protein in an OFC. Subjects will be randomized to two doses of Viaskin Peanut patch or matched placebo (1:1:1) and then will undergo a 5044 mg of peanut protein OFC at week 52, designed to investigate the efficacy, safety and immunologic effects of Viaskin Peanut patch treatment for peanut allergy. Active Viaskin Peanut patch dosing will be with 100 ?g and 250 ?g patches applied every 24 hours and Viaskin placebo patch dosing will be with a placebo (no antigen) patch applied every 24 hrs. At 52 weeks, a 5044 mg of peanut protein OFC will occur. After the 52-week OFC the subject will be unblinded. In the unlikely event that an active subject on active treatment passes the week 52 OFC and has a peanut-specific IgE<2 kUA/L, he/she will discontinue dosing for up to 20 weeks. Sustained unresponsiveness (defined in Section 1.1) will be assessed with a 5044 mg of peanut protein OFCs, followed by an open feeding at 8 weeks, and if negative, again at 20 weeks. Those who pass the OFC after 20 weeks off treatment will be instructed to add peanut to their diet. Those that fail either of these OFCs will resume dosing as described in section 3. Subjects who fail the week 52 OFC, either active or placebo will dose with the 250 ?g dose from the time of unblinding (~ week 52) through week 130. After the 52-week OFC, placebo-treated subjects who do not demonstrate sustained unresponsiveness, will cross-over to active treatment at a dose of 250 ?g daily for a total of 30 months (130 weeks) of active therapy. At the end of study, all subjects will undergo a 5044 mg of peanut protein OFC on treatment; those who pass the OFC will have treatment discontinued and will have an OFC at 8 weeks and 20 weeks, to assess for sustained unresponsiveness off of therapy. Throughout the protocol, all subjects will remain on a peanut-free diet for the duration of active therapy and through any challenges after therapy is completed. | ||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M397ZURMSI | ||||||||||||||
| Subjects: | 86 | ||||||||||||||
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| Assays: | None | ||||||||||||||
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| SDY1538: Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity | ||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||
| Description: | Infection is the most common cause of death in early life, especially for newborns and can be reduced by immunization but insufficient knowledge of how vaccines protect the very young limits their optimal use. To gain insight into how vaccines induce protection of the most vulnerable, our project employs two novel approaches studying newborn responses to hepatitis B vaccine (HBV): (a) systems biology that uses technologies which comprehensively measure global changes in molecules such as transcriptomics (RNA) and proteomics (proteins), as well as cell composition of the blood and (b) use of human newborn blood components, collected prior to immunization, to model vaccine responses in vitro (outside the body). Characterizing vaccine-induced molecular patterns (signatures) that correspond to vaccine-mediated protection will accelerate development and optimization of vaccines against early life infections of major global health importance. | |||||||||||||||||||||||||||
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| DOI: | 10.21430/M35PWV2M56 | |||||||||||||||||||||||||||
| Subjects: | 727 | |||||||||||||||||||||||||||
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| SDY1550: Baked Egg or Egg Oral Immunotherapy for Children With Egg Allergy (CoFAR7) | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | This is a multi-center, randomized, open label study to investigate sustained unresponsiveness induction and safety of Baked Egg vs. Egg OIT, for OFC documented egg allergy, in individuals who pass a 2 gm baked egg protein OFC. All eligible subjects will receive a double-blind placebo controlled baked egg OFC. Individuals who pass the baked egg OFC will then have a double-blind placebo controlled egg OFC. Those who react at a cumulative dose of <= 1444 mg of egg white protein will be randomized 1:1 to Baked Egg or Egg OIT. Approximately 40 of the first individuals who do not pass the initial baked egg food challenge will be assigned to Egg OIT and are the Egg OIT assignment group. Those who tolerate more than 1444 mg of egg white protein on the egg OFC will not be eligible for the study and will be followed per site standard of care. All eligible and enrolled subjects will have a 1 year and a 2 year OFC. | |||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3UFZVM91I | |||||||||||||||
| Subjects: | 187 | |||||||||||||||
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| Assays: | None | |||||||||||||||
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| SDY1854: GI-ARS Efficacy study (180 Days) of Subcutaneous Filgrastim (PBI/BM5) in Rhesus Macaques after Partial Body Irradiation | ||||||||||||||||||
| Status: | Updated | |||||||||||||||||
| Description: | Rhesus macaques were exposed to partial-body irradiation with 5% bone marrow sparing to assess the effect of Neupogen (filgrastim, granulocyte colony stimulating factor [G-CSF]) to mitigate the associated myelosuppression when administered at 24, 72, or 120 hourse post irradiation. A secondary objective was to assess the effect of Neupogen on the mortality or morbidity of the hematopoietic (H)- acute radiation syndrome (ARS) and concomitant acute gastrointestinal radiation syndrome (GI-ARS), prolonged GI injury, acute and chronic kidney injury (AKI, CKI respectively) and delayed lung injury characteristic of delayed effects of acute radiation exposure (DEARE). NHP were exposed to 10 (N=20 males) or 11 Gy (N=28 males) with 6 MV LINAC-derived photons at approximately 0.80 Gy/min. All NHP received medical management. NHP were dosed daily with control article (5% dextrose in water) initiated on day 1 post-exposure or Neupogen (10 ug/kg) initiated on day 1, day 3, or day 5 until recovery (absolute neutrophil count [ANC] >= 1,000 cells/uL for 3 consecutive days). Keywords: rhesus macaques, Macaca mulatta, radiation, natural history, radiation sickness, hematopoietic, gastrointestinal, lung, hematology, metabolomics, histology, filgrastim, RNCP |
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| DOI: | 10.21430/M3ZE7NMJN9 | |||||||||||||||||
| Subjects: | 48 | |||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||
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| SDY2002: Natural History of the Gastrointestinal Acute Radiation Syndrome (GI-ARS) in Rhesus Macaques Following Partial Body Irradiation (2.5% Bone Marrow Sparing) | |||||||||
| Status: | Updated | ||||||||
| Description: | A nonhuman primate model of acute, partial-body, high dose, irradiation (6 megavolt linear accelerator-derived photons delivered at 0.80 Gy minute-1) with 2.5% bone marrow sparing was used to assess the severity and natural history of the acute GI-ARS and associated, concurrent H-ARS and AKI consequent to 12 Gy irradiation. The primary endpoint was survival and secondary objectives focused on a) natural history components and morbidity of GI-ARS (d1-30 post exposure), b) acute kidney injury (AKI, d1-30+ post exposure), c) available database for lung and heart, d) organ-specific biomarkers: plasma- and tissue-based biomarkers for radiation dose and multi-organ injury. Assess the ability to predict DEARE (lung, heart, prolonged GI, kidney). All animals received subject-based medical management. rhesus macaques, Macaca mulatta, radiation, natural history, radiation sickness, hematopoietic, gastrointestinal, lung, hematology, histology, metabolomics, proteomics, lipidomics, bile acid, RNCP |
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| DOI: | 10.21430/M3TQH2ZN7E | ||||||||
| Subjects: | 42 | ||||||||
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| Clinical Assessments: | None | ||||||||
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| SDY2058: GI-ARS Efficacy study (180 Days) of Subcutaneous Filgrastim or Pegfilgrastim in Rhesus Macaques after Partial Body Irradiation (PBI/BM2.5) | |||||||
| Status: | Updated | ||||||
| Description: | Rhesus macaques were exposed to partial-body irradiation with 2.5% bone marrow sparing to assess the effect of Neupogen (filgrastim, granulocyte colony stimulating factor [G-CSF]) or Neulasta (pegfilgrastim, pegG-CSF) to mitigate the associated myelosuppression when administered at 24 or 72 hours post irradiation. A secondary objective was to assess the effect of Neupogen or Neulasta on the mortality or morbidity of the hematopoietic (H)- acute radiation syndrome (ARS) and concomitant acute gastrointestinal radiation syndrome (GI-ARS), prolonged GI injury, acute and chronic kidney injury (AKI, CKI respectively) and delayed lung injury characteristic of delayed effects of acute radiation exposure (DEARE). NHP were exposed to 10 Gy with 6 MV LINAC-derived photons at approximately 0.80 Gy/min. All NHP received medical management. NHP were dosed daily or weekly with control article (5% dextrose in water, or D5W), daily with Neupogen, or weekly with Neulasta. D5W was initiated on day 1 post-exposure. Neupogen (10 ug/kg) administration was initiated on days 1 or 3 post-exposure until recovery (absolute neutrophil count [ANC] >= 1,000 cells/uL for 3 consecutive days). Neulasta (300 ug/kg) administration was initiated on day 1 (days 1, 8, 15) or day 3 (days 3, 11, 17). Keywords: rhesus macaques, Macaca mulatta, radiation, natural history, radiation sickness, hematopoietic, gastrointestinal, lung, hematology, metabolomics, filgrastim, pegfilgrastim, RNCP |
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| DOI: | 10.21430/M3CXBS8APJ | ||||||
| Subjects: | 44 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY2225: Novel Mobile Device Application to Improve Adherence | ||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||
| Description: | This is a prospective, multi-center, randomized controlled study of subjects, children aged 11-17, during the first year after cardiac transplantation. Subjects will be assigned to receive the intervention (TPP) or the standard care (control arm). Subjects and parent/guardians assigned to the TPP intervention arm will use the application to perform daily health monitoring, to document medication administration, and to communicate with the research team (via automated text messaging) for a period up to 12 months post-transplantation. Subjects and parents/guardians assigned to the Control Group will receive standard clinical care per site procedures. | |||||||||||||||||||||
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| DOI: | 10.21430/M3OXUQCLD8 | |||||||||||||||||||||
| Subjects: | 26 | |||||||||||||||||||||
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| Publications: | None | |||||||||||||||||||||
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| Assays: | None | |||||||||||||||||||||
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| SDY2312: Molecular signatures in a Hepatitis B Vaccine-immunized neonatal Tissue Construct in vitro correlate with antibody response in vivo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Only three licensed vaccines are currently approved for neonatal use worldwide with recommended administration around the time of birth: Hepatitis B Vaccine (HBV), Oral Poliovirus Vaccine (OPV) and the Bacille Calmette-Guérin (BCG) tuberculosis vaccine. We have previously shown that baseline (pre-vaccination) and early vaccine-induced systemic changes in global molecular patterns- i.e., “OMIC” signatures -in the days immediately post-immunization can predict subsequent protective humoral and cellular immune responses. However, it is unclear how the exact timing and sequence of neonatal vaccination can affect signatures of immunogenicity and vaccine-induced protection in humans. Herein, we employ our 3-dimensional tissue construct model that was previously used to investigate and replicate human age- specific vaccine responses in vivo, to a) gain insights into vaccine-induced OMIC signatures after single vs combined vaccination and b) investigate the association between human in vitro OMIC signatures and human in vivo hepatitis B antibody titers, a universally-accepted correlate of vaccine-induced protection, from the same study participants. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/m34t975slb | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 64 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Publications: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY3090: PDI-TCR reveals the dynamics and phenotypes of CD4 T cells in tuberculosis | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Identifying antigen specificity in T cell receptor (TCR) sequences is challenging because of the diversity of the TCR repertoire and the complexity of TCR:antigen recognition. We developed the Peptide-Driven Identification of TCRs (PDI-TCR) assay, which combines in vitro cell expansion with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. PDI-TCR can differentiate true antigen-specific TCR clonotypes from TCRs linked to nonspecific bystander activation by comparing responses to non-overlapping peptide pools. We applied PDI-TCR to Tuberculosis (TB) patients, sampling blood at diagnosis and during treatment, as well as to Mycobacterium tuberculosis (Mtb)-sensitized healthy individuals (IGRA+). Mtb-specific T cells exhibited high diversity, with short-lived effector phenotypes only present in TB at diagnosis, while memory phenotypes were sustained throughout treatment. In contrast, expanded nonspecific T cells were more clonally restricted, displayed a cytotoxic phenotype, and persisted during treatment. | |||||||||||||||
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| DOI: | 10.21430/M35YWYAEUK | |||||||||||||||
| Subjects: | 65 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
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| SDY3689: GI-ARS Efficacy Study in Rhesus Macaques after Partial Body Irradiation (PBI/BM5) - Control Animals | |||||||
| Status: | Updated | ||||||
| Description: | Prior to irradiation, NHP were randomized to either a control (n = 15) or treated (n = 15) cohort. On Study Day (SD) 0, each NHP was sedated, restrained, and transported to the LINAC facility. They were then placed on the LINAC treatment table and positioned within the lighted radiation field in such a way that the whole body was contained within the field, with the exception of the tibiae, ankles, and feet (i.e., the field terminated at the inferior edge of the patella). After positioning, the NHPs were exposed to six (6) megavolt (MV) photons delivered at a dose rate of approximately 0.80 Gy/min, resulting in PBI/BM5 to a targeted dose of 12.0 Gy. Following irradiation, NHP were administered six (6) SC injections of either TA or CA (10 mM histidine buffer in water at 0.1 ml/kg) at 24 ± 2 hour intervals from the time of irradiation. All animals were monitored for complete blood count (CBC), plasma levels of blood urea nitrogen (BUN) and creatinine (Cr), body weight (BW), rectal body temperature (RBT), stool consistency, and clinical hydration status through the end of the in-life phase. Animals received medical management consisting of intravenous (IV) fluids, antibiotics, analgesics, antidiarrheals, antiemetics, blood transfusions, supplemental nutrition, and other support as required. rhesus macaques, Macaca mulatta, radiation, natural history, radiation sickness, gastrointestinal, hematology, histology, cytokines, RNCP Animals were euthanized according to a set of criteria based on clinical signs including activity level, weight loss, and responsiveness to antidiarrheal treatment, or between SD31 and SD35 if criteria were not met during the in-life phase. Survival was analyzed at 15 and 30 days postirradiation. | ||||||
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| DOI: | 10.21430/M3WHI3TIET | ||||||
| Subjects: | 15 | ||||||
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