DR2 DataRelease
Release Date: 06/01/2013
| SDY40: Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population | |||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||
| Description: | We will recruit adult (21-49 years of age), elderly (>50 years), ages as outlined in the RFA, or non-elderly but immunosuppressed (defined as taking at least 10 mg of prednisone daily for at least one month) participants from the Greater New Haven area and rheumatology clinics in the Yale-New Haven Healthcare System. Individuals of either gender and all ethnic groups will be eligible to participate. We will stimulate monocytes and DCs in vitro with ligands of TLRs 1-9 and quantify the efficiency of stimulation by assessment of production of cytokines and inflammatory mediators. TLRs 10 and 11 will not be addressed at this time as ligands are not known. Lineage specific pro-inflammatory cytokines from PBMCs by FACs. We will quantify intracellular levels of TNFα and IL-6 by FACS from PBMCs in suspension on the day of isolation of the cells. This is essential to control for differences in cell composition in PBMCs isolated from different individuals, given the broad range of hematopoietic cells synthesizing TNFα and IL-6. By using multi-color staining of PBMCs with lineage-specific fluorescent antibodies, we will identify lineages positive for intracellular cytokine production at the single cell level, and track potential age-associated changes in cell lineages. Our experimental approach will be to obtain monocytes/macrophages cells from young adult and elderly subjects, define their Mif genotype, and analyze their baseline and stimulus-induced production of MIF. Patient samples for genotyping will be obtained from the pellet of the Ficoll-hypaque isolation of PBMCs and extracted DNA will be analyzed for Mif genotype by established, robotic methodology that requires <1 μg of DNA. Purified monocytes/macrophage will be studied for their baseline and stimulation-induced responses following protocols in place in our laboratory. |
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| Program/Contract: |
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| DOI: | 10.21430/M3EMF3OMS4 | ||||||||||||||||||||||
| Subjects: | 903 | ||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||
| SDY41: Determine whether differences in TLR-responsiveness alter susceptibility to Biodefense priority pathogens using WN virus as a paradigm or responsiveness to vaccination using influenza as a model shared to Semi-Public Workspace (SPW) Project | |||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||
| Description: | The Study's goal is to quantify the innate immune response of macrophages from the three populations identified in the study titled 'Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population', to agents of Biodefense, using West Nile virus infection and influenza vaccination as models. In addition, by recruiting patients who have had West Nile virus infection or received influenza vaccine, we will assess the efficiency of immune responses to these potential agents of bioterrorism. |
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| DOI: | 10.21430/M3KDRIKJOB | ||||||||||||||||||||||
| Subjects: | 903 | ||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||
| SDY61: Systems Biology of 2007 Influenza Vaccination in Humans (See companion studies SDY269 2008 / SDY270 2009 / SDY271 Role for CaMKIV in the Regulation of Antibody Responses to Influenza Vaccine) | |||||||||||
| Status: | New | ||||||||||
| Description: | Using a systems biology approach to study innate and adaptive responses to influenza vaccination in humans during the 2007-2008 influenza season. | ||||||||||
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| DOI: | 10.21430/M3FH0SA2W0 | ||||||||||
| Subjects: | 12 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY62: Vaccination with drifted variants of H5 hemagglutinin protein elicits a broadened antibody response | |||||||
| Status: | New | ||||||
| Description: | Substantial H5 influenza HA directed immunity is elicited after vaccination of human subjects who had been previously immunized with a drifted H5 HA variant. We sought to investigate the characteristics of H5 HA specific immune responses in more depth by developing an animal model of H5 HA vaccination using drift variants of recombinant H5 HA proteins. HA proteins derived from influenzas A/Vietnam/1203/04 (Clade 1) and A/Indonesia/05/05 (Clade 2.1) were chosen. The sequence of vaccination consisted of two doses of homologous protein, followed by one additional dose of the homologous or heterologous, drifted HA protein. Each dose of HA was combined with CpG as an adjuvant and was injected subcutaneously. All the animals exhibited a serum IgG antibody response that cross-reacted with both HAs in an ELISA. However, those animals that received the drifted variant exhibited higher reactivity to the heterologous HA. Competitive ELISA of serum from drift-variant recipients showed evidence of antibody focusing towards the drifted HA, suggesting modification of the response towards improved cross-reactivity, though development of neutralizing antibodies was limited. Nevertheless, animals were protected against live-virus challenge, and passive transfer of serum was sufficient to confer protection to otherwise naive mice, indicating that both neutralizing and non-neutralizing antibodies offer some degree of protection. These findings suggest that pre-vaccination against H5 influenza has the potential to prime immunity against emerging drifted H5 strains, and could also lower the dose requirements of vaccination in the event of a pandemic. | ||||||
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| DOI: | 10.21430/M3RH4FT7XC | ||||||
| Subjects: | 86 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY64: Aerosol vaccination in mice | |||||||||
| Status: | New | ||||||||
| Description: | Evaluation of the parameters required for effective aerosol delivery of influenza virus in mice using controlled 20 and 30 m MMAD particle aerosols as proof of concept for LAIV aerosol delivery | ||||||||
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| DOI: | 10.21430/M3DU77M662 | ||||||||
| Subjects: | 36 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY146: Immune response evaluation in patients treated with TNF-alpha blockade (anti-TNF) | |||||||
| Status: | New | ||||||
| Description: | This project is to develop and apply the University of Rochester Program for Biodefense of Immunocompromised Populations (URPBIP) to the systematic study of human immune function with the goal of identifying defective mechanisms of immune response in patients treated with TNF-alpha blockade (anti-TNF). Studies are designed to detect changes that are likely to be induced by sustained TNF-alpha neutralization in the immune homeostasis and immune responsiveness of B-cells, T-cells and Dendritic cells. Although the study is not specifically designed to understand immune function in the elderly, the inclusion of a subset of patients and controls over and under 50 may result in the discovery of age-specific defects. | ||||||
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| DOI: | 10.21430/M3QXQFGTK5 | ||||||
| Subjects: | 225 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY162: Immunologic and genomic signatures of response to Hepatitis C Virus infection. | |||||||
| Status: | New | ||||||
| Description: | Examine the immune response in primary immune cells from subjects who have spontaneously cleared HCV compared to HCV chronically infected subjects | ||||||
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| DOI: | 10.21430/M3TI5NZ7VL | ||||||
| Subjects: | 20 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY165: Characterization of in vitro Stimulated B Cells from Human Subjects | |||||||||||
| Status: | New | ||||||||||
| Description: | During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. RNA microarray and functional analyses showed that proliferating CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation. | ||||||||||
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| DOI: | 10.21430/M3GTK55VEV | ||||||||||
| Subjects: | 15 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY167: VRC304 - A Phase I Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine (VRC-AVIDNA036-00-VP) Encoding for the Influenza Virus H5 Hemagglutinin Protein in Healthy Adults | |||||||||||||
| Status: | New | ||||||||||||
| Description: | The primary objective was to evaluate the safety and tolerability of an investigational vaccine VRC-AVIDNA036-00-VP in humans at doses 1 mg and 4 mg administered intramuscularly using a needle-free injection system. The secondary objectives included evaluation of whether VRC-AVIDNA036-00-VP (at doses 1 mg and 4 mg) induced antibodies as assessed by an HAI assay at Day 0 and Week 12. Exploratory analyses included evaluation of the immunogenicity of VRC-AVIDNA036-00-VP at doses 1 mg and 4 mg using intracellular cytokine staining, ELISpot, neutralizing antibody assay, HAI assay to H1 or H3HA or other immunological assays at time intervals between Day 0 and Week 42. | ||||||||||||
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| DOI: | 10.21430/M3SGHW16WZ | ||||||||||||
| Subjects: | 45 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY196: Responses to Influenza Vaccination in Systemic Lupus Year 1 2005-2006 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3ABJS44K6 | ||||||||||||
| Subjects: | 62 | ||||||||||||
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| SDY197: Responses to Influenza Vaccination in Systemic Lupus Year 2 2006-2007 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3FD1QTLQQ | ||||||||||||
| Subjects: | 63 | ||||||||||||
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| SDY198: Responses to Influenza Vaccination in Systemic Lupus Year 3 2007-2008 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3D393V41D | ||||||||||||
| Subjects: | 74 | ||||||||||||
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| SDY199: Responses to Influenza Vaccination in Systemic Lupus Year 4 2008-2009 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M39YLN3479 | ||||||||||||
| Subjects: | 69 | ||||||||||||
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| SDY200: Responses to Influenza Vaccination in Systemic Lupus Year 5 2009-2010 | |||||||||||
| Status: | New | ||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||
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| DOI: | 10.21430/M3ZR6IH181 | ||||||||||
| Subjects: | 73 | ||||||||||
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| SDY201: Responses to Influenza Vaccination in Systemic Lupus Year 6 2010-2011 | |||||||||||
| Status: | New | ||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||
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| DOI: | 10.21430/M35J0WA7CR | ||||||||||
| Subjects: | 34 | ||||||||||
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