DR43 DataRelease

SDY1490: Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH)
Status: New
Description: Our primary goal is to test the hypothesis that a defined subset of pediatric liver tx recipients can safely and durably withdraw from IS. A fundamental research question is whether 35% of selected pediatric liver transplant recipients can be withdrawn from IS and achieve operational tolerance. We will conduct a multi-center, longitudinal study to determine the safety and efficacy of ISW with concomitant translational studies to develop and validate a fingerprint which predicts operational tolerance. Pediatric recipients of deceased or living donor liver txs will be screened for eligibility and those eligible will begin ISW. Participants will undergo gradual ISW over no less than 36 weeks and no more than 52 weeks with frequent monitoring of liver tests. All participants will be followed for 48 months ensuring a minimum of 36 months of follow-up after successful ISW.
Program/Contract:
ProgramContract
ITN: Collaborative Network for Clinical Research on Immune Tolerance Network IMMUNOSUPPRESSION WITHDRAWAL FOR STABLE PEDIATRIC LIVER TRANSPLANT RECIPIENTS
DOI: 10.21430/M3CJTCGUDP
Subjects: 161
Study PI, contact:
NameOrganizationSite
Sandy Feng University of California, San Francisco University of California, San Francisco
Publications:
Evidence of Chronic Allograft Injury in Liver Biopsies From Long-term Pediatric Recipients of Liver Transplants.. Gastroenterology Dec 2018. doi: 10.1053/j.gastro.2018.08.023 [Pubmed: 30144432]
Posttransplant biopsy risk for stable long-term pediatric liver transplant recipients: 451 percutaneous biopsies from two multicenter immunosuppression withdrawal trials.. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons May 2019. doi: 10.1111/ajt.15255 [Pubmed: 30614623]
Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.. Hepatology (Baltimore, Md.) May 2021. doi: 10.1002/hep.31520 [Pubmed: 32786149]
Improvements in Disease-Specific Health-Related Quality of Life of Pediatric Liver Transplant Recipients During Immunosuppression Withdrawal.. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society May 2021. doi: 10.1002/lt.25963 [Pubmed: 33280227]
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01638559]
Assays:
Assay TypeNumber of Exp. Samples
Array 133
Clinical Assessments:None

SDY1644: Urban Environmental Factors and Childhood Asthma (URECA) (ICAC-07)
Status: New
Description: The purpose of this study is to determine the way environmental factors (like the components of inner-city household dust) affect immune system development and symptoms of asthma in inner city children. The study is divided into three periods, as the subjects age from birth to 10 years old. Each age bracket will explore different objectives and endpoints. Study Objectives/Hypotheses: Subjects age 0 to 3 years old: Environmental factors in the inner city adversely influence the development of the immune system to promote cytokine dysregulation, allergy, and recurrent wheezing by age 3. Children who have had a viral lower respiratory infection and have developed cytokine dysregulation by age 3 are at increased risk for the development of asthma by age 6. Subjects age 4 to 7 years old: There is a unique pattern of immune development that is driven by specific urban exposures in early life, and this pattern of immune development is characterized by: 1) impairment of antiviral responses and 2) accentuation of Th2-like responses (e.g. cockroach-specific Interleukin-13(IL-13)). The clinical effects of these changes in immune development are frequent virus-induced wheezing and allergic sensitization by 3-4 years of age, and these characteristics synergistically increase the risk of asthma at age 7 years. Subjects age 7 to 10 years old: There are unique combinations of environmental exposures (cockroach allergens, indoor pollutants [Environmental Tobacco Smoke (ETS) and Nitrogen Dioxide (NO2)], lack of microbial exposure), and family characteristics (stress, genetic factors related to innate immunity) that synergistically promote asthma onset, persistence, and morbidity in urban neighborhoods. These exposures and characteristics influence immune expression and lung development during critical periods of growth, resulting in specific asthma phenotypes. Subjects age 10 to 16 years old: To determine the wheezing, asthma and atopy phenotypes in minority children growing up in poor urban neighborhoods as they develop from birth through adolescence.
Program/Contract:
ProgramContract
Inner City Asthma Consortium (ICAC) RFA-AI-13-036 INNER CITY ASTHMA CONSORTIUM 3 (ICAC3)
DOI: 10.21430/M3H1YHLR5Z
Subjects: 609
Study PI, contact:
NameOrganizationSite
James Gern University of Wisconsin School of Medicine and Public Health University of Wisconsin School of Medicine and Public Health
Publications:
Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study.. BMC immunology Dec 2006. doi: 10.1186/1471-2172-7-29 [Pubmed: 17156490]
The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population.. BMC pulmonary medicine May 2009. doi: 10.1186/1471-2466-9-17 [Pubmed: 19426496]
Characterization of regulatory T cells in urban newborns.. Clinical and molecular allergy : CMA Jul 2009. doi: 10.1186/1476-7961-7-8 [Pubmed: 19586545]
Parental characteristics, somatic fetal growth, and season of birth influence innate and adaptive cord blood cytokine responses.. The Journal of allergy and clinical immunology Nov 2009. doi: 10.1016/j.jaci.2009.08.021 [Pubmed: 19895995]
Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort.. American journal of respiratory and critical care medicine Jul 2010. doi: 10.1164/rccm.200904-0637OC [Pubmed: 20194818]
Retention strategies and predictors of attrition in an urban pediatric asthma study.. Clinical trials (London, England) Aug 2010. doi: 10.1177/1740774510373798 [Pubmed: 20571137]
Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study).. The Journal of allergy and clinical immunology Apr 2011. doi: 10.1016/j.jaci.2010.12.1122 [Pubmed: 21333343]
Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study.. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Jun 2011. doi: 10.1111/j.1365-2222.2011.03712.x [Pubmed: 21481021]
Longitudinal relationship of early life immunomodulatory T cell phenotype and function to development of allergic sensitization in an urban cohort.. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Mar 2012. doi: 10.1111/j.1365-2222.2011.03882.x [Pubmed: 22092655]
Antiviral IFN-g responses of monocytes at birth predict respiratory tract illness in the first year of life.. The Journal of allergy and clinical immunology May 2012. doi: 10.1016/j.jaci.2012.02.033 [Pubmed: 22460071]
Comparison of the etiology of viral respiratory illnesses in inner-city and suburban infants.. The Journal of infectious diseases Nov 2012. doi: 10.1093/infdis/jis504 [Pubmed: 23014674]
Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children.. The Journal of allergy and clinical immunology Sep 2014. doi: 10.1016/j.jaci.2014.04.018 [Pubmed: 24908147]
Influence of early-life exposures on food sensitization and food allergy in an inner-city birth cohort.. The Journal of allergy and clinical immunology Jan 2015. doi: 10.1016/j.jaci.2014.06.033 [Pubmed: 25129677]
Relation between stress and cytokine responses in inner-city mothers.. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Nov 2015. doi: 10.1016/j.anai.2015.07.021 [Pubmed: 26409873]
The influence of atopy and asthma on immune responses in inner-city adults.. Immunity, inflammation and disease Mar 2016. doi: 10.1002/iid3.96 [Pubmed: 27042305]
Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families.. American journal of respiratory and critical care medicine Mar 2017. doi: 10.1164/rccm.201602-0272OC [Pubmed: 27654103]
Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy.. The Journal of allergy and clinical immunology Sep 2017. doi: 10.1016/j.jaci.2016.10.052 [Pubmed: 28089873]
Early-life home environment and risk of asthma among inner-city children.. The Journal of allergy and clinical immunology Apr 2018. doi: 10.1016/j.jaci.2017.06.040 [Pubmed: 28939248]
Development of Asthma in Inner-City Children: Possible Roles of MAIT Cells and Variation in the Home Environment.. Journal of immunology (Baltimore, Md. : 1950) Mar 2018. doi: 10.4049/jimmunol.1701525 [Pubmed: 29431692]
Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and Relationship to Maternal Smoking in Pregnancy.. The journal of allergy and clinical immunology. In practice Sep 2018. doi: 10.1016/j.jaip.2017.12.028 [Pubmed: 29449165]
Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma.. The Journal of allergy and clinical immunology Dec 2018. doi: 10.1016/j.jaci.2018.02.019 [Pubmed: 29518416]
Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort.. American journal of respiratory and critical care medicine Jan 2019. doi: 10.1164/rccm.201801-0190OC [Pubmed: 30079758]
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00114881]
Assays:None
Clinical Assessments:None

SDY1720: A Retrospective Multicenter Study to Determine Clinical Outcomes in Subjects Previously Enrolled in the CTOTC-03 Study (CTOTC-14)
Status: New
Description: This study is a multicenter, non?randomized, retrospective study to collect long term (5 years post?transplant +/- 6 months) clinical outcome data on subjects previously enrolled in the CTOTC-03 study.
Program/Contract:
ProgramContract
Clinical Trials in Organ Transplantation in Children (CTOT-C) RFA-AI-12-005 VIRAL TRIGGERS OF ALLOIMMUNITY AND AUTOIMMUNITY IN PEDIATRIC LUNG TRANSPLANTATION (CTOTC-03)
DOI: 10.21430/M3G3QHV9UG
Subjects: 35
Study PI, contact:
NameOrganizationSite
Stuart Sweet Washington University School of Medicine Washington University School of Medicine
Publications:
Role of Circulating MicroRNAs in the Immunopathogenesis of Rejection After Pediatric Lung Transplantation.. Transplantation Oct 2017. doi: 10.1097/TP.0000000000001595 [Pubmed: 27941431]
Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study.. Pediatric transplantation Sep 2017. doi: 10.1111/petr.13011 [Pubmed: 28639398]
Anellovirus loads are associated with outcomes in pediatric lung transplantation.. Pediatric transplantation Feb 2018. doi: 10.1111/petr.13069 [Pubmed: 29082660]
Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Dec 2019. doi: 10.1111/ajt.15505 [Pubmed: 31216376]
Epidemiology and persistence of rhinovirus in pediatric lung transplantation.. Transplant infectious disease : an official journal of the Transplantation Society Dec 2020. doi: 10.1111/tid.13422 [Pubmed: 32686323]
Resources:
ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT00891865]
Assays:None
Clinical Assessments:None

SDY1781: Proinflammatory IgG Fc structures in patients with severe COVID-19
Status: New
Description: Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fc? receptor Fc?RIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.
Program/Contract:
ProgramContract
SeroNet Mechanisms and Duration of Immunity to SARS-CoV-2
DOI: 10.21430/M33D4Y9RTM
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Proinflammatory IgG Fc structures in patients with severe COVID-19.. Nature immunology Jan 2021. doi: 10.1038/s41590-020-00828-7 [Pubmed: 33169014]
Resources:
Supplementary Fig. 1 https://static-content.springer.com/esm/art%3A10.1038%2Fs41590-020-00828-7/MediaObjects/41590_2020_828_MOESM1_ESM.pdf]
Assays:None
Clinical Assessments:None

SDY1789: Regimen verification phase: Sequential optimization of dose and schedule of PfSPZ Vaccine, verified by randomized, controlled, double-blind immunization and controlled human malaria infection in malaria-naive, healthy adult volunteers in Germany
Status: New
Description: The study is to take place at Institut fur Tropenmedizin, Eberhard Karls Universitat Tubingen, Tubingen Germany. The study has two phases: 1) dose optimization, and 2) regimen verification. In the first phase groups A, B1, B2, C1, C2 and C3 will be vaccinated sequentially in a pre-specified order, followed by homologous CHMI with 3,200 PfSPZ Challenge (NF54) three weeks after last vaccine injection. Dose optimization phase A: 9x10^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35x10^6 PfSPZ on Days 0 and 7 (n = 6) B2: 1.35x10^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7x10^6 PfSPZ on Day 0 (n = 6) C2: 2.7x10^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7x10^6 PfSPZ on Days 0, 7 and 28 (n = 6) In parallel to CHMI with PfSPZ Challenge (NF54) during the optimization phase, a total of nine volunteers will receive either 800, 1,600 or 3,200 PfSPZ Challenge (7G8) (PfSPZ Challenge (7G8) dose finding) to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) in malaria-naive healthy adult volunteers. PfSPZ Challenge (7G8) dose finding/infection D1: 800 PfSPZ (n = 3) D2: 1,600 PfSPZ (n = 3) D3: 3,200 PfSPZ (n = 3) Subsequently, the shortest efficacious regimen (V1) and a three-dose regimen (Day 0, 7 and 28) of the highest safe dose (V2) will be selected and verified against placebo (normal saline (NS)). Groups V1 and V2 will be vaccinated at approximately the same time and undergo repeat CHMI three and eight weeks after the last immunization. Volunteers will either receive PfSPZ Vaccine or NS as placebo. Allocation will be random and double blind. Repeat CHMI will be done with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), given in a randomized sequence. All immunizations are given by direct venous inoculation (DVI). Regimen verification phase V1: Shortest efficacious regimen (n = 12) against placebo (n = 6) V2: Maximum regimen (n = 12) against placebo (n = 6) P1: Placebo for V1 group (n=6) P2 Placebo for V2 group (n=6).
Program/Contract:
ProgramContract
DMID Sanaria Grant Program Genome-Wide Sieve Analysis And Immunological Validation To Identify Targets Of Protective Efficacy In Field Trials Of A Whole-Organism Malaria Vaccine
DOI: 10.21430/M3ABFZ7TY8
Subjects: 18
Study PI, contact:
NameOrganizationSite
Benjamin Mordmuller Institute of Tropical Medicine, University of Tuebingen Institute of Tropical Medicine, University of Tuebingen
Publications:None
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02704533]
Assays:None
Clinical Assessments:None

SDY1798: Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions
Status: New
Description: SARS-CoV-2 is the cause of a pandemic with growing global mortality. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with ChIRP-MS data from three other RNA viruses defined viral specificity of RNA-host protein interactions. Targeted CRISPR screens revealed that the majority of functional RNA-binding proteins protect the host from virus-induced cell death, and comparative CRISPR screens across seven RNA viruses revealed shared and SARS-specific antiviral factors. Finally, by combining the RNA-centric approach and functional CRISPR screens, we demonstrated a physical and functional connection between SARS-CoV-2 and mitochondria, highlighting this organelle as a general platform for antiviral activity. Altogether, these data provide a comprehensive catalog of functional SARS-CoV-2 RNA-host protein interactions, which may inform studies to understand the host-virus interface and nominate host pathways that could be targeted for therapeutic benefit.
Program/Contract:
ProgramContract
SeroNet Mechanisms and Duration of Immunity to SARS-CoV-2
DOI: 10.21430/M3NPEVXJWP
Subjects: 0
Study PI, contact:
NameOrganizationSite
Scott Boyd Stanford Stanford University
Publications:
Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions.. Cell Apr 2021. doi: 10.1016/j.cell.2021.03.012 [Pubmed: 33743211]
Resources:
sequencing data (ChIRP-seq and CRISPR screens) https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE167341]
Source code for all of the analysis as well as the raw and processed data for the chirp ms experiments. https://github.com/juliabelk/sarscov2_chirp_ms]
Assays:None
Clinical Assessments:None

SDY1800: Durable SARS-CoV-2 B cell immunity after mild or severe disease
Status: New
Description: Multiple studies have shown loss of severe acute respiratory syndrome coronavirus 2-specific (SARS-CoV-2-specific) antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from coronavirus disease 2019 (COVID-19). However, memory B cells (MBCs) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multidimensional flow cytometric analysis of S protein receptor binding domain-specific (S-RBD-specific) MBCs in cohorts of ambulatory patients with COVID-19 with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 days (range, 39-104 days) after symptom onset. We detected S-RBD-specific class-switched MBCs in 13 of 14 participants, failing only in the individual with the lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBCs (rMBCs) made up the largest proportion of S-RBD-specific MBCs in both cohorts. FCRL5, a marker of functional memory on rMBCs, was more dramatically upregulated on S-RBD-specific rMBCs after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched rMBCs that resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after mild or severe disease.
Program/Contract:
ProgramContract
SeroNet Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2 (JH-EPICS)
DOI: 10.21430/M3YQ1SXVS6
Subjects: 14
Study PI, contact:
NameOrganizationSite
Sabra Klein W. Harry Feinstone Department of Molecular Microbiology and Immunology W. Harry Feinstone Department of Molecular Microbiology and Immunology
Publications:
Durable SARS-CoV-2 B cell immunity after mild or severe disease.. The Journal of clinical investigation Apr 2021. doi: 10.1172/JCI145516 [Pubmed: 33571162]
Resources:
Assays:None
Clinical Assessments:None

SDY1813: Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases
Status: New
Description: T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens and precisely measure virus-specific CD4+ and CD8+ T cells, we study epitope-specific T cell responses of 99 convalescent coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (HLA) alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells.
Program/Contract:
ProgramContract
SeroNet SARS-CoV-2 correlates of protection in a Latino-origin population
DOI: 10.21430/M3F1F8OJDN
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases.. Cell reports. Medicine Feb 2021. doi: 10.1016/j.xcrm.2021.100204 [Pubmed: 33521695]
Resources:
Wuhan-Hu-1 RNA isolate https://www.ncbi.nlm.nih.gov/nuccore/MN908947]
ORF10 protein https://www.ncbi.nlm.nih.gov/protein/YP_009725255.1]
Nucleocapsid phosphoprotein https://www.ncbi.nlm.nih.gov/protein/YP_009724397.2]
ORF8 protein https://www.ncbi.nlm.nih.gov/protein/YP_009724396.1]
ORF7a protein https://www.ncbi.nlm.nih.gov/protein/YP_009724395.1]
ORF6 protein https://www.ncbi.nlm.nih.gov/protein/YP_009724394.1]
Membrane glycoprotein https://www.ncbi.nlm.nih.gov/protein/YP_009724393.1]
envelope protein https://www.ncbi.nlm.nih.gov/protein/YP_009724392.1]
ORF3a protein https://www.ncbi.nlm.nih.gov/protein/YP_009724391.1]
surface glycoprotein https://www.ncbi.nlm.nih.gov/protein/YP_009724390.1]
orf1ab polyprotein https://www.ncbi.nlm.nih.gov/protein/YP_009724389.1]
Immune Epitope Database http://www.iedb.org/reference/1037798]
Assays:None
Clinical Assessments:None

SDY1829: Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells
Status: New
Description: The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was `exhausted? or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-?B signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.
Program/Contract:
ProgramContract
SeroNet SARS-CoV-2-reactive tissue-resident memory T cells in healthy and cancer subjects
DOI: 10.21430/M3A57H738Q
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8 T cells.. Science immunology Jan 2021. doi: 10.1126/sciimmunol.abe4782 [Pubmed: 33478949]
Resources:
GEO https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153931]
Scripts https://github.com/vijaybioinfo/COVID19_2020]
Assays:None
Clinical Assessments:None

SDY1831: Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity
Status: New
Description: Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by immunoglobulin G (IgG), with an IgG subclass ratio skewed toward elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2-specific antibody binding to the inflammatory receptor Fc?RIIIa. Based on these correlational studies, we propose that spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy.
Program/Contract:
ProgramContract
SeroNet High-Throughput Dried Blood Spot (HT-DBS) Technologies in SARS COV-2 Serology and Vaccinology
DOI: 10.21430/M3B6163WG1
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.. Cell reports. Medicine Jul 2021. doi: 10.1016/j.xcrm.2021.100329 [Pubmed: 34151306]
Resources:
GenBank https://www.ncbi.nlm.nih.gov/nuccore/MN908947]
Assays:None
Clinical Assessments:None

SDY1832: Immunological imprinting of the antibody response in COVID-19 patients
Status: New
Description: In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
Program/Contract:
ProgramContract
SeroNet Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses
DOI: 10.21430/M3EMGZH7G6
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Immunological imprinting of the antibody response in COVID-19 patients.. Nature communications Jun 2021. doi: 10.1038/s41467-021-23977-1 [Pubmed: 34145263]
Resources:
Assays:None
Clinical Assessments:None

SDY1877: Ethmoidal sinus scRNA from CRSwNP and CRSsNP
Status: New
Description: scRNA-Seq data from ethmoidal sinus samples from adult human sbjects with chronic rhinosinusitis with nasal polypsosis (n=6) and chronic rhinosinusitis without nasal polyposis (n=6)
Program/Contract:
ProgramContract
Asthma and Allergic Diseases Cooperative Research Centers Type 2 Mucosal Inflammation Elicited Through an LTE4/GPR99-Dependent Pathway
DOI: 10.21430/M392GKBPXD
Subjects: 11
Study PI, contact:
NameOrganizationSite
Nora Barrett Brigham and Women's Hospital Brigham and Women's Hospital
Publications:
Allergic inflammatory memory in human respiratory epithelial progenitor cells.. Nature Aug 2018. doi: 10.1038/s41586-018-0449-8 [Pubmed: 30135581]
Resources:
Allergic inflammatory memory in human respiratory epithelial progenitor cells https://www.nature.com/articles/s41586-018-0449-8]
Assays:
Assay TypeNumber of Exp. Samples
Microscopy 12
RNA sequencing 12
Clinical Assessments:
Allergic_rhinitis
Aspirin_tolerant
Asthma
Diagnosis
Polyp_grade
Prior_surgeries
Sinus_infections

SDY1880: Multicenter Mayo Genomics Trial (GEN-04)
Status: New
Description: Gene expression profiling is used to study the activity of genes. Each gene has an "on/off" switch that controls how they are expressed in a cell, as well as a "volume control" that increases or decreases the level of expression of a particular gene as necessary. Researchers want to see if the presence and abundance of certain transcripts in a kidney biopsy at one year after transplant can predict which kidneys will have reduced function over time.
Program/Contract:
ProgramContract
Genomics of Transplantation Cooperative Research Program (GEN) RFA-AI-10-019 Intragraft expression to Predict Future GFR Decline in Kidney Transplantation (Gen-04)
DOI: 10.21430/M31W8DCC1W
Subjects: 494
Study PI, contact:
NameOrganizationSite
Mark Stegall Mayo Clinic College of Medicine Mayo Clinic College of Medicine
Publications:
Predicting Individual Renal Allograft Outcomes Using Risk Models with 1-Year Surveillance Biopsy and Alloantibody Data.. Journal of the American Society of Nephrology : JASN Oct 2016. doi: 10.1681/ASN.2015070811 [Pubmed: 26961348]
Acute Antibody-Mediated Rejection in Renal Transplantation: Current Clinical Management.. Current transplantation reports Jun 2014. doi: 10.1007/s40472-014-0012-y [Pubmed: 27656351]
A method to reduce variability in scoring antibody-mediated rejection in renal allografts: implications for clinical trials - a retrospective study.. Transplant international : official journal of the European Society for Organ Transplantation Feb 2019. doi: 10.1111/tri.13340 [Pubmed: 30179275]
Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.. Clinical transplantation Dec 2021. doi: 10.1111/ctr.14456 [Pubmed: 34717009]
Resources:
NIH RePORTER https://reporter.nih.gov/project-details/8190061]
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT01782586]
Assays:
Assay TypeNumber of Exp. Samples
RNA sequencing 270
Clinical Assessments:None

SDY1886: Multiscale PHATE identifies multimodal signatures of COVID-19
Status: New
Description: Multiscale PHATE is a machine learning novel tool for dimensionality reduction and data exploration that can be applied to biological data sets to learn and visualize
Program/Contract:
ProgramContract
Non-NIH funding programs Women's Health Research at Yale Pilot Project Program
DOI: 10.21430/M3D4FZNYFR
Subjects: 2170
Study PI, contact:
NameOrganizationSite
Julie Hussin Yale University Montreal Heart Institute/ Universite de Montreal
Guy Wolf Yale University Mila-Quebec AI institute/ Universite de Montreal
Akiko Iwasaki Yale University Yale University/ Yale New Haven Hospital
Publications:
Multiscale PHATE identifies multimodal signatures of COVID-19.. Nature biotechnology Feb 2022. doi: 10.1038/s41587-021-01186-x [Pubmed: 35228707]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 412
Clinical Assessments:None

SDY1912: Mouse blood gene expression after administration of 137 Cesium
Status: New
Description: In the current study, we investigated the gene expression response of blood cells of mice that were injected with variable amounts of 137Cs. We isolated total RNA from peripheral blood from mice with 0 (control), 158, 191, 215 and 259 uCi cesium source amount on days 2, 3, 5, 7 and 14 days after injection. Using Agilent Mouse Whole Genome microarrays, we identified x genes that were significantly differentially expressed across the 14-day time course of this study. We identified common biological functions affected that persisted across the 14-day study.
Program/Contract:
ProgramContract
Centers for Medical Countermeasures Against Radiation Consortium (CMCRC) RFA-AI-19-012 Center For High-Throughput Minimally-Invasive Radiation Biodosimetry RFA-AI-19-012
DOI: 10.21430/M37BKVG03K
Subjects: 32
Study PI, contact:
NameOrganizationSite
Shanaz Ghandhi Columbia University Medical Center Columbia University Medical Center
Publications:
Dose and Dose-Rate Effects in a Mouse Model of Internal Exposure to 137Cs. Part 1: Global Transcriptomic Responses in Blood.. Radiation research Nov 2020. doi: 10.1667/RADE-20-00041 [Pubmed: 32931585]
Resources:
GEO https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118616]
Assays:
Assay TypeNumber of Exp. Samples
RNA sequencing 152
Clinical Assessments:None

SDY1916: Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity
Status: New
Description: Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve responses to injected vaccines. Mice coadministered a pharmacological inhibitor of elastase, or lacking elastase, developed high-affinity serum IgG and IgA antibodies after immunization with alum-adsorbed protein vaccines, including the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). These mice also developed broader antigen-specific CD4+ T cell responses, including high Th1 and T follicular helper (Tfh) responses. Interestingly, in the absence of elastase activity, mucosal SIgA responses were induced after systemic immunization with alum as adjuvant. Importantly, lack or suppression of elastase activity enhanced the magnitude of anti-SARS-CoV-2 spike subunit 1 (S1) antibodies, and these antibodies reacted with the same epitopes of spike 1 protein as sera from COVID-19 patients. Therefore, suppression of neutrophil elastase could represent an attractive strategy for improving the efficacy of alum-based injected vaccines for the induction of broad immunity, including mucosal immunity.
Program/Contract:
ProgramContract
SeroNet Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID)
DOI: 10.21430/M38FW5ZQHE
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity.. Proceedings of the National Academy of Sciences of the United States of America Aug 2021. doi: 10.1073/pnas.2102435118 [Pubmed: 34353890]
Resources:
Assays:None
Clinical Assessments:None

SDY1917: Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients
Status: New
Description: There is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin's lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.
Program/Contract:
ProgramContract
SeroNet Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID)
DOI: 10.21430/M383VCI57N
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients.. Cell & bioscience Nov 2021. doi: 10.1186/s13578-021-00713-2 [Pubmed: 34802457]
Resources:
Assays:None
Clinical Assessments:None

SDY1924: A multiomics study in a Japanese rheumatoid arthritis cohort
Status: New
Description: A multiomics study in a Japanese rheumatoid arthritis cohort
Program/Contract:
ProgramContract
NIH Program KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance)
DOI: 10.21430/M36KC4L9G2
Subjects: 54
Study PI, contact:
NameOrganizationSite
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
RNA sequencing 54
Clinical Assessments:None

SDY1927: Corticosteroid treatment in COVID-19 modulates host inflammatory responses and transcriptional signatures of immune dysregulation
Status: New
Description: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-2019 (COVID-19), a respiratory disease that varies in severity from mild to severe/fatal. Several risk factors for severe disease have been identified, notably age, male sex, and pre-existing conditions such as diabetes, obesity, and hypertension. Several advancements in clinical care have been achieved over the past year, including the use of corticosteroids (e.g., corticosteroids) and other immune-modulatory treatments that have now become standard of care for patients with acute severe COVID-19. While the understanding of the mechanisms that underlie increased disease severity with age has improved over the past few months, it remains incomplete. Furthermore, the molecular impact of corticosteroid treatment on host response to acute SARS-CoV-2 infection has not been investigated. In this study, a cross-sectional and longitudinal analysis of Ab, soluble immune mediators, and transcriptional responses in young (< or = 65 years) and aged (> 65 years) diabetic males with obesity hospitalized with acute severe COVID-19 was conducted. Additionally, the transcriptional profiles in samples obtained before and after corticosteroids became standard of care were compared. The analysis indicates that severe COVID-19 is characterized by robust Ab responses, heightened systemic inflammation, increased expression of genes related to inflammatory and pro-apoptotic processes, and reduced expression of those important for adaptive immunity regardless of age. In contrast, COVID-19 patients receiving steroids did not show high levels of systemic immune mediators and lacked transcriptional indicators of heightened inflammatory and apoptotic responses. Overall, these data suggest that inflammation and cell death are key drivers of severe COVID-19 pathogenesis in the absence of corticosteroid therapy.
Program/Contract:
ProgramContract
SeroNet SARS-CoV-2 correlates of protection in a Latino-origin population
DOI: 10.21430/M3WIUTT8OD
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Corticosteroid treatment in COVID-19 modulates host inflammatory responses and transcriptional signatures of immune dysregulation.. Journal of leukocyte biology Dec 2021. doi: 10.1002/JLB.4COVA0121-084RR [Pubmed: 34730254]
Resources:
RNA-Sequencing data https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA751085]
Assays:None
Clinical Assessments:None

SDY1928: Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response
Status: New
Description: There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1? and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M31K1V0I9F
Subjects: 133
Study PI, contact:
NameOrganizationSite
Lynne Sykes Imperial College London Institute of Reproductive and Developmental Biology
Publications:
Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.. Nature communications Feb 2022. doi: 10.1038/s41467-022-28620-1 [Pubmed: 35190561]
Resources:
PRJEB41427 https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB41427]
paper_link https://www.nature.com/articles/s41467-022-28620-1]
Source Data for Figures https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28620-1/MediaObjects/41467_2022_28620_MOESM7_ESM.xlsx]
Assays:
Assay TypeNumber of Exp. Samples
16S rRNA gene sequencing 385
Luminex xMAP 385
Clinical Assessments:None

SDY1930: The Metabolic Signature of the Placenta in SPTB
Status: New
Description: The placenta is metabolically active and supports the growth of the fetus. We hypothesize that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may result in spontaneous preterm birth (SPTB). To explore this hypothesis, we performed a nested cased control study of metabolomic signatures in placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (?38 weeks gestation). To control for the effects of gestational age on placenta metabolism, we also studied a subset of metabolites in non-laboring preterm and term Rhesus monkeys. Comprehensive quantification of metabolites demonstrated a significant elevation in the levels of amino acids, prostaglandins, sphingolipids, lysolipids, and acylcarnitines in SPTB placenta compared to term placenta. Additional quantification of placental acylcarnitines by tandem mass spectrometry confirmed the significant elevation in SPTB human, with no significant differences between midgestation and term placenta in Rhesus macaque. Fatty acid oxidation as measured by the flux of 3H-palmitate in SPTB placenta was lower than term. Collectively, significant and biologically relevant alterations in the placenta metabolome were identified in SPTB placenta. Altered acylcarnitine levels and fatty acid oxidation suggest that disruption in normal substrate metabolism is associated with SPTB.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3HS37CJNW
Subjects: 0
Study PI, contact:
NameOrganizationSite
Rebecca Simmons University of Pennsylvania and Children's Hospital of Philadelphia Department of Pathology and Laboratory Medicine
Publications:
The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth.. International journal of molecular sciences Feb 2020. doi: 10.3390/ijms21031043 [Pubmed: 32033212]
Resources:
paper link https://www.mdpi.com/1422-0067/21/3/1043]
Source of Placenta samples https://clinicaltrials.gov/ct2/show/NCT02441335]
related study SDY1899 https://www.immport.org/shared/search?text=SDY1899]
Assays:None
Clinical Assessments:None

SDY1931: Common Cervicovaginal Microbial Supernatants Alter Cervical Epithelial Function
Status: New
Description: Cervicovaginal (CV) microbiota is associated with vaginal health and disease in non-pregnant women. Recent studies in pregnant women suggest that specific CV microbes are associated with preterm birth (PTB). While the associations between CV microbiota and adverse outcomes have been demonstrated, the mechanisms regulating the associations remain unclear. As the CV space contains an epithelial barrier, we postulate that CV microbiota can alter the epithelial barrier function. We investigated the biological, molecular, and epigenetic effects of Lactobacillus crispatus, Lactobacillus iners, and Gardnerella vaginalis on the cervical epithelial barrier function and determined whether L. crispatus mitigates the effects of lipopolysaccharide (LPS) and G. vaginalis on the cervical epithelial barrier as a possible mechanism by which CV microbiota mitigates disease risk. Ectocervical and endocervical cells treated with L. crispatus, L. iners, and G. vaginalis bacteria-free supernatants alone or combined were used to measure cell permeability, adherens junction proteins, inflammatory mediators, and miRNAs. Ectocervical and endocervical permeability increased after L. iners and G. vaginalis exposure. Soluble epithelial cadherin increased after exposure to L. iners but not G. vaginalis or L. crispatus. A Luminex cytokine/chemokine panel revealed increased proinflammatory mediators in all three bacteria-free supernatants with L. iners and G. vaginalis having more diverse inflammatory effects. L. iners and G. vaginalis altered the expression of cervical-, microbial-, and inflammatory-associated miRNAs. L. crispatus mitigated the LPS or G. vaginalis-induced disruption of the cervical epithelial barrier and reversed the G. vaginalis-mediated increase in miRNA expression. G. vaginalis colonization of the CV space of a pregnant C57/B6 mouse resulted in 100% PTB. These findings demonstrate that L. iners and G. vaginalis alter the cervical epithelial barrier by regulating adherens junction proteins, cervical immune responses, and miRNA expressions. These results provide evidence that L. crispatus confers protection to the cervical epithelial barrier by mitigating LPS- or G. vaginalis-induced miRNAs associated with cervical remodeling, inflammation, and PTB. This study provides further evidence that the CV microbiota plays a role in cervical function by altering the cervical epithelial barrier and initiating PTB. Thus, targeting the CV microbiota and/or its effects on the cervical epithelium may be a potential therapeutic strategy to prevent PTB.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3WYLOVYKD
Subjects: 0
Study PI, contact:
NameOrganizationSite
Lauren Anton Perelman School of Medicine at the University of Pennsylvania Department of Obstetrics and Gynecology, Maternal and Child Health Research Center
Publications:
Common Cervicovaginal Microbial Supernatants Alter Cervical Epithelial Function: Mechanisms by Which Lactobacillus crispatus Contributes to Cervical Health.. Frontiers in microbiology Oct 2018. doi: 10.3389/fmicb.2018.02181 [Pubmed: 30349508]
Resources:
paper link https://www.frontiersin.org/articles/10.3389/fmicb.2018.02181/full]
Assays:None
Clinical Assessments:None

SDY1932: Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans
Status: New
Description: Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.
Program/Contract:
ProgramContract
SeroNet Longitudinal Analyses of Antibody Responses to SARS-CoV-2
DOI: 10.21430/M3T4B7MGV4
Subjects: 0
Study PI, contact:
NameOrganizationSite
Publications:
Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.. Viruses Nov 2021. doi: 10.3390/v13112325 [Pubmed: 34835131]
Resources:
Supplementary Materials https://www.mdpi.com/article/10.3390/v13112325/s1]
Assays:None
Clinical Assessments:None

SDY1600: Mapping Immune Responses to CMV in Renal Transplantation
Status: Updated
Description: We propose to characterize in depth the relationship between CMV, the compromised host immune response and tissue injury using high-throughput technologies and novel statistical and computational approaches in the setting of solid organ transplant. This setting is unique as it provides the ability to understand viral infection and host tissue injury from the beginning, as the donor organ, when transplanted into a recipient, is generally pristine and without any substantive injury, and will experience exposure or reactivation of CMV only after engraftment. For the sake of homogeneity, we have elected to restrict these studies to kidney transplants, given that this is the most common organ transplanted, has a robust immune response profile that resembles most of the other organ transplants, and is the first organ system to be chosen for the conduct of all phase 1/2/3 pharmaceutical clinical trials. The primary goal of this proposal is to advance the field by creating a unique resource of highly annotated clinical phenotype and multidimensional omics data on the immune response to CMV during primary infection and reactivation. The secondary objective is to gain new insights into how CMV contributes to chronic allograft rejection and identify new approaches to patient management and therapy. These studies have broad applications to understanding the host:pathogen interactions in immunocompromised individuals and their downstream effects in other chronic disease states.
Program/Contract:
ProgramContract
Human Immunology Project Consortium (HIPC) RFA-AI-15-041 Mapping Immune Responses To CMV In Renal Transplant Recipients (UCLA)
DOI: 10.21430/M30V1NQBF0
Subjects: 413
Study PI, contact:
NameOrganizationSite
David Elashoff UCLA UCLA
Alexander Hoffman UCLA UCLA
Suphamai (Michael) Bunnapradist UCLA UCLA
Flavio Vincenti UCSF UCSF
Publications:
NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant.. JCI insight Nov 2021. doi: 10.1172/jci.insight.153175 [Pubmed: 34609965]
Acute and Chronic Changes in Gene Expression After CMV DNAemia in Kidney Transplant Recipients.. Frontiers in immunology Nov 2021. doi: 10.3389/fimmu.2021.750659 [Pubmed: 34867983]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 431
Luminex xMAP 168
RNA sequencing 172
Clinical Assessments:None
Back to top