DR31 DataRelease
Release Date: 06/19/2019
| SDY1267: Malaria Vaccine in Healthy Adults | |||||||
| Status: | New | ||||||
| Description: | Approximately 168 healthy, malaria-naive volunteers aged 18 - 50 years, divided into 2 groups (84 in each group), will receive either one dose of Ad35.CS.01 followed by two doses of 257049 at monthly intervals or 3 doses of 257049 vaccine at monthly intervals. Of these, a maximum of 138 vaccinated volunteers will be challenged with P. falciparum infected mosquitoes. The challenge will occur 2 weeks following the third immunization. A group of up to 18 infectivity controls will begin participation in the study at the challenge stage. These controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3FVO9SM7Y | ||||||
| Subjects: | 67 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1302: Prematurity, Respiratory outcomes, Immune System, and Microbiome Study (PRISM) | |||||||
| Status: | New | ||||||
| Description: | Enrollment min/max Age Unit is weeks Post-menstrual age at birth. | ||||||
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| DOI: | 10.21430/M3LBDA3IAM | ||||||
| Subjects: | 225 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1341: Vaginal Virome and Preterm Birth (See companion study SDY1206) | |||||||
| Status: | New | ||||||
| Description: | Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Culture-independent sequencing of vaginal bacterial communities demonstrates community characteristics are associated with preterm birth, although none are specific enough to apply clinically. Viruses are important components of the vaginal microbiome and have dynamic relationships with vaginal bacterial communities. The authors hypothesized that vaginal eukaryotic DNA viral communities either alone or in the context of bacterial communities are associated with preterm birth. In this nested case-control study, serial mid-vaginal swabs were obtained at routine prenatal visits and bacterial communities and eukaryotic viral communities were characterized from extracted DNA. Viral communities were analyzed according to presence/absence of viruses, diversity, dynamics over time, and association with bacterial community data obtained from the same specimens. | ||||||
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| DOI: | 10.21430/M31K9QN0OM | ||||||
| Subjects: | 60 | ||||||
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| SDY1363: Suspect screening for chemicals in pregnant women | |||||||
| Status: | New | ||||||
| Description: | In utero exposure to environmental chemicals can adversely impact pregnancy outcomes and childhood health but minimal biomonitoring data exist on the majority of chemicals used in commerce. | ||||||
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| DOI: | 10.21430/M3ZWNRQPCG | ||||||
| Subjects: | 75 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1417: Pregnancy induces an earlier chronotype in both mice and women | |||||||
| Status: | New | ||||||
| Description: | Wrist actigraphy was obtained for two weeks before conception and then throughout pregnancy. Chronotype was measured by determining the time of sleep onset from the actigraphy profile of each 24-hour period (12 PM to 12 PM the next day) during the first (gestational weeks 4 through 13), second (weeks 14 through 27) and third trimesters (week 28 until delivery). | ||||||
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| DOI: | 10.21430/M34RFPUKX4 | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1436: Novel correlates of protection against influenza A(H1N1)pdm virus infection | |||||||
| Status: | New | ||||||
| Description: | Novel influenza virus vaccines that target more conserved epitopes of influenza viruses, specifically the hemagglutinin stalk and neuraminidase, are currently being developed. However, HA stalk antibodies have not yet been correlated with protection from natural infection in humans. We performed a household transmission study to identify alternative correlates of protection in naturally exposed individuals. Pre-existing antibody levels measured in hemagglutinin inhibition (HI) and ELISA assays were linked to the risk of PCR-confirmed infection and disease after exposure. We identified 50% protective titers and levels for HI, full-length HA, NA, and HA stalk. HI, HA stalk and NA antibodies all remained protective against infection and disease when adjusted for age. When additionally adjusted for other antibody levels, we found HI and HA stalk, but not NA antibodies to be independently protective against infection. Similar reductions were observed for symptomatic influenza. Furthermore, ELISA assays were found to accurately predict seroconversion in addition to traditional HI assays. This study establishes HA stalk antibodies as an additional correlate of protection against influenza virus infection in humans in a natural exposure scenario and supports the HA stalk as a target for novel universal influenza virus vaccine candidates. | ||||||
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| DOI: | 10.21430/M3HXYMFM42 | ||||||
| Subjects: | 366 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1439: Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events. | |||||||
| Status: | New | ||||||
| Description: | Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than _35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses. | ||||||
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| DOI: | 10.21430/M3LJTCB0M1 | ||||||
| Subjects: | 196 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1473: Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth | ||||||||||
| Status: | New | |||||||||
| Description: | Preterm birth is the leading cause of infant mortality, and prematurity is further associated with serious morbidities in later life. Genetic and environmental risk factors play a role in the susceptibility to preterm birth. Despite numerous studies, the genetic basis for preterm birth remains poorly defined. We investigated the presence of rare, possibly risk associated nucleotide variants in mothers with spontaneous preterm births (SPTB). The first set of mothers with family history of recurrent preterm births was of northern Finnish origin. An additional set of mothers (sister pairs, both giving birth preterm) of European origin was also studied. Whole exome sequencing identified multiple rare, likely damaging HSPA1L variants in several families affected by SPTB, and this gene was associated with the glucocorticoid receptor signaling pathway. Potential involvement of one of the HSPA1L variants in SPTB was further supported by large GWAS dataset. In addition, this variant alters protein post-translational modification potential, and thus may affect protein stability and its function as a chaperone. | |||||||||
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| DOI: | 10.21430/M31DFMAKJW | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY1474: Anthropoid primate specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length | |||||||
| Status: | New | ||||||
| Description: | The proper timing of delivery is critical during pregnancy; if too early or too late, the baby will be at risk of serious health problems and even death. Corticotropin-releasing hormone (CRH) is a protein that can be detected in maternal blood, and its concentration correlates with the timing of birth. In humans and other anthropoid primates, CRH is made by the placenta, whereas in other mammals, it is produced in a specialized region of the brain. To understand the regulation and evolution of this key protein, we inserted the human CRH gene and nearby regions into the mouse genome, which resulted in human CRH expression in the mouse placenta. Mouse litters that make CRH in their placentas are born later than control mice, showing that CRH can directly affect birth timing. Using our mouse model, we then selectively deleted a remnant of an ancient retrovirus that is normally found in the DNA of anthropoid primates and demonstrated that this specific region controls expression of CRH in the placenta. Deletion of this region also restored normal birth timing in the mice by eliminating CRH production from the placenta. We propose that retroviral regulation of CRH in the placenta may be a mechanism of controlling birth timing in humans and other anthropoid primates. | ||||||
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| DOI: | 10.21430/M3AZYDHB5Z | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1487: CD33 recruitment inhibits IgE-mediated anaphylaxis and desensitizes mast cells to allergen | |||||||
| Status: | New | ||||||
| Description: | Allergen immunotherapy for patients with allergies begins with weekly escalating doses of allergen under medical supervision to monitor and treat IgE mast cell?mediated anaphylaxis. There is currently no treatment to safely desensitize mast cells to enable robust allergen immunotherapy with therapeutic levels of allergen. Here, we demonstrated that liposomal nanoparticles bearing an allergen and a high-affinity glycan ligand of the inhibitory receptor CD33 profoundly suppressed IgE-mediated activation of mast cells, prevented anaphylaxis in Tg mice with mast cells expressing human CD33, and desensitized mice to subsequent allergen challenge for several days. We showed that high levels of CD33 were consistently expressed on human skin mast cells and that the antigenic liposomes with CD33 ligand prevented IgE-mediated bronchoconstriction in slices of human lung. The results demonstrated the potential of exploiting CD33 to desensitize mast cells to provide a therapeutic window for administering allergen immunotherapy without triggering anaphylaxis. | ||||||
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| DOI: | 10.21430/M37G7PMJ7E | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1502: Platelets attach to lung ILC2 expressing PSGL-1 and influence ILC2 function | |||||||
| Status: | New | ||||||
| Description: | Electron microscopy demonstrates that mouse lung ILC2 expressing PSGL-1 have platelets attached to their surface and that platelet depletion reduces lung ILC2 proliferation and Th2 cytokines suggesting ILC2 function is influenced by attachment to platelets | ||||||
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| DOI: | 10.21430/M3208RB6VB | ||||||
| Subjects: | 26 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1503: Transcriptomes From Human Tissue Biopsies During Pregnancy | |||||||
| Status: | New | ||||||
| Description: | Spontaneous preterm labor is one of the leading causes of preterm birth and is associated with pathological changes in both the uterine myometrium and cervix The aim of this study was to understand how these changes occur at a cellular level. Samples of 310 single cell transcriptomes were derived from biopsies of tissues obtained from 4 pregnant women in their third trimester that underwent planned cesarean hysterectomies because of suspected morbidly adherent placentas. Using single cell transcriptomic analyses, different cell types obtained from cervical and uterine biopsies during late pregnancy were delineated using marker genes. Expressed genes were cross validated using the Human Protein Atlas. The cells were separated into 5 major groups using unbiased clustering of marker genes: endothelial, leukocytes, epithelial, smooth muscle, and stromal cells. Genes that separated the different cell types were observed to be genes whose coordinated expression drives that cell type?s specific biological function. In addition to cell type specific genes, enriched expression of genes implicated in active inflammatory processes were also observed. The single cell catalogue created during this study gives a deeper understanding of pathologies that occur during childbirth, including preterm births. | ||||||
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| DOI: | None | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY67: Bioinformatics Approach to 2010-2011 TIV Influenza A/H1N1 Vaccine Immune Profiling | |||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||
| Description: | Aim 1: Characterize Immune Profiles Over Time, Aim 2: Correlate Immune Profiles with Vaccine Immunogenicity,Aim 3: Replication of Immune Profiles and Verification of Models | ||||||||||||||||||||||||
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| DOI: | 10.21430/M3OYWCJHO1 | ||||||||||||||||||||||||
| Subjects: | 159 | ||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||
| SDY887: Defective signaling in aging, influenza vaccination 2007 SLVP015 | |||||||
| Status: | Updated | ||||||
| Description: | Pilot year. Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to indentify benchmarks of immunological health, influenza vaccination was used in 10 young (20-30 years) and 19 older subjects (60 to 89 years) as models for strong and weak immune responses, respectively. Serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation were measured. Using machine learning, nine variables predicting antibody response with 84% accuracy were identified. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. | ||||||
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| DOI: | 10.21430/M33JMYFLF1 | ||||||
| Subjects: | 29 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1041: CMV CD8 T Cells | |||||||
| Status: | Updated | ||||||
| Description: | We present human T cell responses in multiple sites including blood, lymphoid, mucosal and secretory tissues of 20 CMV seropositive donors. Overall, CMV-specific T cells were maintained in distinct distribution patterns, either predominant in blood, bone marrow (BM) and lung, or lymph nodes (LN) with the frequency and function in blood distinct from tissues. Together, our results reveal tissue T cell reservoirs for CMV control, with global effects on T cell homeostasis over the human lifespan. | ||||||
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| DOI: | 10.21430/M3MIPLU7ZU | ||||||
| Subjects: | 20 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1178: Islet Transplantation in Type 1 Diabetes (CIT-07) and Extended Follow Up after Islet Transplantation in Type 1 Diabetes (CIT-08) | |||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||
| Description: | The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population is individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. Subjects in CIT07, a single arm Phase 3 license-enabling study, received induction and maintenance immunosuppression in an open-label fashion consisting of rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), etanercept, sirolimus and low-dose tacrolimus. | ||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3P7Q1ZRXJ | ||||||||||||||||||||||||||||||
| Subjects: | 48 | ||||||||||||||||||||||||||||||
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| SDY1387: Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy (ICAC-29) | ||||||||||
| Status: | Updated | |||||||||
| Description: | ICAC-29/MUPPITS-1 is a prospective, longitudinal, nested case-control study designed to identify changes in gene transcription predictive of and associated with asthma exacerbations in children ages 6 to 17 years with difficult-to-control, exacerbation-prone asthma. Participants will be followed prospectively for the onset of a cold and a subsequent asthma exacerbation. An internet-based asthma and cold symptom diary will be accessed by participants using a hand-held device. When the participant reports development of a cold, a clinic visit will be scheduled as soon as possible (within 48 hours of cold symptom onset) to collect blood and nasal samples. A second clinic visit will occur 4-6 days from the onset of cold symptoms to obtain samples after the initial cold, but prior to the use of systemic corticosteroids. Participants will be followed for up to two colds or approximately 6 months after Visit 0, whichever comes first. | |||||||||
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| DOI: | 10.21430/M3Q1C6388O | |||||||||
| Subjects: | 227 | |||||||||
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| Clinical Assessments: | None | |||||||||