DR62 DataRelease
Release Date: March 2026
New Studies: 26
Updated Studies: 4
New Studies
| SDY2311: Uncovering the Dynamics of Immune Cell Populations in the First Week of Life: The Interplay of Neutrophils and Breastfeeding | ||||||||||||||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||||||||||||||
| Description: | The first few days of life are characterized by rapid external and internal changes that require rapid host adaptations. Despite growing evidence of the impact of this period on an individual’s lifelong health trajectory, this period remains largely uncharted. To decipher key factors associated with changes in peripheral blood cell composition we conducted a stringently standardized, high-throughput immune phenotyping investigation on 796 newborns across diverse settings (The Gambia, West Africa and Papua New Guinea, Australasia) in the framework of a Human Immunology Project Consortium study. Samples were collected twice from each newborn during the first week of life and analyzed via high throughput flow cytometry with an unbiased automated gating algorithm to capture cell compositional changes at an unprecedented level of detail. We found that immune cell composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes with age/day of life were most pronounced in the innate myeloid compartment. While there was minimal impact of sex, season of birth, mother’s age or origin (i.e., environmental and genetic background), breastfeeding and vaccination were strongly associated with increase in cell counts of peripheral blood neutrophils and monocytes. Our results may suggest a possible association of initiation of breastfeeding with changes in immune ontogeny, and thus possibly host immune-mediated protection from infection. These data begin to outline a specific window of opportunity for interventions that can deliberately direct immune ontogeny. | |||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3UN6865OL | |||||||||||||||||||||||||||||||||
| Subjects: | 85 | |||||||||||||||||||||||||||||||||
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| Publications: | None | |||||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||||||||||||||
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| SDY3318: Permissive omicron breakthrough infections in individuals with binding or neutralizing antibodies to ancestral SARS-CoV-2 | |||||||
| Status: | New | ||||||
| Description: | In a longitudinal cohort study, pre-breakthrough infection sera for Omicron breakthroughs were analyzed via different assays. | ||||||
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| DOI: | 10.21430/M32I9Z7CCG | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3366: mRNA vaccination boosts T cell memory in COVID-19 recovered individual | ||||||||||
| Status: | New | |||||||||
| Description: | TODO | |||||||||
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| DOI: | 10.21430/M3A78AFO0H | |||||||||
| Subjects: | 20 | |||||||||
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| Clinical Assessments: | None | |||||||||
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| SDY3404: Novel Epitopes of the Influenza Virus N1 Neuraminidase Targeted by Human Monoclonal Antibodies | ||||||||||
| Status: | New | |||||||||
| Description: | We observed escape mutations on the head domain of the N1 protein around the enzymatic site (S364N, N369T, and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D, and Q313K/R). This work increases our understanding of how human antibody responses target the N1 protein. | |||||||||
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| DOI: | 10.21430/M3LTO54ZWD | |||||||||
| Subjects: | 4 | |||||||||
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| Clinical Assessments: | None | |||||||||
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| SDY3407: Predicting influenza vaccine antibody responses | |||||||
| Status: | New | ||||||
| Description: | Development and validation of two sets of scores, the Simple-Test score (STS) and the No-Test score (NTS) that can predict subjects' vaccine-elicited antibody responses measured by the HAI titers composite score. Data from human cohort vaccine study conducted in Athens, GA, USA across four influenza seasons (2016-2017, 2017-2018, 2018-2019, 2019-2020) were used for the analysis. | ||||||
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| DOI: | 10.21430/M359ECB7CU | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3410: BCG vaccination induces antibacterial effector functions among Vdelta1/3 T cells that are associated with protection against tuberculosis | |||||||
| Status: | New | ||||||
| Description: | Gamma delta T cells expressing a Vdelta1/3 T cell receptor are enriched at mucosal surfaces, but their role in protection against Mycobacterium tuberculosis is largely unknown. We used multimodal single-cell RNA sequencing, mass cytometry, and flow cytometry to profile gamma delta T cells from human infants and macaques after protective vaccination with Mycobacterium bovis bacillus Calmette-Guerin. A subset of Vdelta1/3 T cells in BCG-vaccinated human infants shows evidence of clonal expansion and differentiation into Mtb-reactive cytotoxic effector cells. In macaques, intravenous BCG induces pro-inflammatory and cytotoxic responses to Mtb among Vdelta1/3 T cells that are enriched in the airway compared to the blood. Finally, the frequency of cytokine-expressing Vdelta1/3 T cells in the airway is associated with protection against Mtb challenge. Thus, Vdelta1/3 T cells are activated by BCG and accumulate in the lung, where they upregulate cytotoxic and pro-inflammatory functions that may contribute to protective immunity against Mtb. | ||||||
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| DOI: | 10.21430/M3TM9Y230F | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3417: CELL2025_Grifoni | |||||||
| Status: | New | ||||||
| Description: | In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell epitope regions (CTERs). We showed that SARS-CoV-2 CTER-specific T cells cross-reactively recognize sequences from multiple Betacoronavirus subgenera based on experimental data ran using Flow Cytometry. We also show that incorporating CTERs from non-spike proteins significantly enhanced T cell cross-reactivity potential and HLA coverage compared to T cells targeting only spike based on predictions analyses based on the HLA typing of the donors studied. | ||||||
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| DOI: | 10.21430/M37VGLVR69 | ||||||
| Subjects: | 29 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3420: Effects of obesity on influenza challenge | |||||||
| Status: | New | ||||||
| Description: | Obese ferrets were challenged with the H9N2 strain A/Hong Kong/1073/1999 virus, monitored and nasal washed to determine shared variants of genomic segments using RT-PCR in order to determine if obesity has an effect on genetic diversity. | ||||||
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| DOI: | 10.21430/M3A995A0T1 | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3421: Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination. | |||||||
| Status: | New | ||||||
| Description: | The authors sought to identify gene expression signatures that correlate with the induction of high anti-stalk antibody titers post vaccination with adjuvanted-inactivated vaccines | ||||||
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| DOI: | 10.21430/M3047F16BM | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3422: Longitudinal analysis of influenza vaccination and DNA methylation regulation | ||||||||||
| Status: | New | |||||||||
| Description: | DNA methylation changes to components of the RIG-I pathway are associated with vaccine effectiveness. Computational analysis performed via HAI assay, paired t-test, and differently methylated sites assess how they contribute to the immune response. | |||||||||
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| DOI: | 10.21430/M3X9OYUT1R | |||||||||
| Subjects: | 96 | |||||||||
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| Clinical Assessments: | None | |||||||||
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| SDY3423: Influenza Viruses Suitable for Studies in Syrian Hamsters | |||||||
| Status: | New | ||||||
| Description: | The authors show that the PR8-HY genetic backbone mentioned previously also increases the replication of several seasonal influenza viruses in Syrian hamsters compared to the authentic viruses. | ||||||
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| DOI: | 10.21430/M35JGM9DTH | ||||||
| Subjects: | 102 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3424: Utilizing Language Models to Forecast Antibody Activity against Influenza A | |||||||
| Status: | New | ||||||
| Description: | The model, built with the MAMMAL framework for biologics discovery, predicts antibody-antigen interactions solely based on sequence information. Its performance was evaluated by testing under various data split conditions to simulate real-world scenarios. | ||||||
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| DOI: | 10.21430/M3DZ445DXW | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY3425: Human Microglia Engraftment in Mice | ||||||||||
| Status: | New | |||||||||
| Description: | The primary goal of this study is to quantify the extent of donor cell integration and to confirm the near-complete replacement of endogenous mouse microglia with genetically unmodified human pluripotent stem cell-derived microglia (hMGs), and to assess the survival and phenotypic characteristics of the transplanted cells in the context of species-specific CSF1R signaling differences. Methods involve isolating hMG progenitors from human embryonic stem cells (modified with EGFP knock-in for traceability), neonatal intracerebral transplantation into immunodeficient mice with humanized CSF1 ligand, and a PLX5622 treatment to deplete host microglia. Brains are harvested post PLX5622 treatment for dissociation and multi-color flow cytometry analysis, including markers such as EGFP (to identify donor hMGs), human and mouse-specific CD45/CD11b, and viability dyes, with gating strategies to quantify chimerism levels and population purity. | |||||||||
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| DOI: | 10.21430/M3KX778CBB | |||||||||
| Subjects: | 6 | |||||||||
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| Publications: | None | |||||||||
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| Clinical Assessments: | None | |||||||||
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| SDY3433: Single cell transcriptomic profiling of eosinophils and airway immune cells in childhood asthma | ||||||||||
| Status: | New | |||||||||
| Description: | Background Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular heterogeneity but remains inadequate in capturing granulocytes, particularly in tissue compartments, due to technical limitations. Objective To enhance granulocyte recovery in scRNA-seq, we employed nasal lavage samples from children with asthma, leveraging the 10x Genomics Flex platform combined with a customized data processing pipeline. Methods Nasal lavage samples were processed without prior manipulation to avoid technical artifacts such as lysis or stimulation. Granulocyte recovery was optimized using fixation to preserve cell quality and advanced computational techniques to separate low RNA content cells from background noise. Cell-type proportions were validated against histologic and bulk-RNA data. Results The optimized approach achieved an >16-fold increase in eosinophil detection compared to standard methods. This method successfully captured eosinophils, neutrophils, and other major cell types in proportions consistent with histologic and bulk-RNA assessments, with no biased loss of cell types. Phenotypic comparisons between children with high-eosinophil and low-eosinophil asthma uncovered significant transcriptional differences, cell composition and distinct biological pathways in granulocytes, immune cells, and epithelial cells. Additionally, distinct subpopulations of eosinophils and neutrophils with unique functional profiles were identified, which were uniquely associated with high- and low-eosinophil asthma phenotypes, highlighting the complexity of airway granulocyte inflammation. Conclusions This study provides a framework for efficient capture of granulocytes in tissue compartments, overcoming traditional limitations. The resulting dataset serves as a valuable resource for understanding airway granulocyte biology and inflammation, enabling detailed exploration of asthma pathogenesis. Furthermore, this approach facilitates large-scale, multi-center translational studies and advances personalized therapeutic strategies for airway diseases. | |||||||||
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| DOI: | 10.21430/M319LOKP8C | |||||||||
| Subjects: | 6 | |||||||||
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| Publications: | None | |||||||||
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| Clinical Assessments: | None | |||||||||
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| SDY3435: Thin-film freeze-drying of an influenza virus mRNA vaccine with blebs | ||||||||||
| Status: | New | |||||||||
| Description: | Assess TFFD impact on particle properties, nanostructure (Cryo-EM, SAXS), RNA integrity (capillary electrophoresis), powder properties (PXRD, mDSC, SEM), and mouse immunogenicity (ELISA, HAI). | |||||||||
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| DOI: | 10.21430/M3H7FVVQ4N | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
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| SDY3440: Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2 | |||||||
| Status: | New | ||||||
| Description: | The investigators evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters | ||||||
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| DOI: | 10.21430/M3A0KEK9MY | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3441: Use of Slow-Delivery Platform Shapes the Host Immune Response to Increase Protection Against Influenza | ||||||||||
| Status: | New | |||||||||
| Description: | The use of a slow-release vaccine platform, VacSIM, can enhance the host immune response and improve protection against influenza infection. In this study, mice were immunized with either Y2 (H1) hemagglutinin (HA) or NG2 (H3) HA and divided into three groups: HA combined with CpG, HA combined with VacSIM and CpG, and VacSIM with CpG alone. Serum and lung samples were collected at various time points to assess the immune response through immunological analyses. | |||||||||
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| DOI: | 10.21430/M3SKDY1QGN | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
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| SDY3442: Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | The authors identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern. | |||||||||||||||
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| DOI: | 10.21430/M3KCQB5GDW | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Publications: | None | |||||||||||||||
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| Assays: | None | |||||||||||||||
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| SDY3443: Immunogenicity of High-resolution in situ structures of hantavirus glycoprotein tetramers | ||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||
| Description: | New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This enabled the determination of a 2.35 Å resolution structure of the membrane-embedded Andes virus (ANDV) glycoprotein tetramer, as well as structures of dimers of tetramers and a complex with antibody ADI-65534. These structures reveal previously uncharacterized features of glycoprotein organization, stability, and pH-sensing. Immunization of mice with self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies compared to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts. To evaluate the immunogenicity of ANDV GPC variants, we synthesized sequences encoding the wildtype (WT) GPC (repGPC-WT), WT GPC with an eVLP tag (repGPC-WT-eVLP), the double modification (DM) GPC (repGPC-DM), and DM GPC with the eVLP tag (repGPC-DM-eVLP) into a plasmid DNA that encodes a self-amplifying replicon RNA (repRNA). In addition to the ANDV GPC open reading frame, repRNA encodes the Venezuelan equine encephalitis virus (VEEV), strain TC-83, replication machinery, which amplifies the antigen-encoding subgenomic message in a target cell. When delivered with the cationic nanocarrier Lipid InOrganic Nanoparticle (LION™), this repRNA/LION platform can transfect muscle cells at the injection site of the vaccinee (Kimura, Leal et al. 2023) and has been shown to drive VLP production from cells transfected with repRNA encoding certain viral glycoprotein antigens (Erasmus, Khandhar et al. 2018, Warner, Archer et al. 2024). After producing the repRNA ANDV GPC plasmids, we generated repRNA, formulated the repRNAs with LIONTM, and proceeded to evaluate these vaccines in mouse immunogenicity studies. Female C57BL/6 mice (n = 10/group) were immunized intramuscularly on days 0 and 35 with either 1 µg or 10 µg of each formulation, as well as an irrelevant antigen repRNA control (Fig. 6A). Blood was collected on days 0, 14, 35, and 49 to evaluate ANDV Gn–Gc-specific antibody binding titers via ELISA and neutralizing antibody titers via rVSV-ANDV-based assays. On day 14, LION/repGPC-DM-eVLP at a 10 µg dose induced a rapid binding antibody response, with mice displaying significantly higher titers relative to repGPC-WT (p = 0.045) and repGPC-DM (p = 0.034), respectively (Fig. 6B). The trend was similar, though not significant, at the 1 µg dose (Fig. 6C). By day 35, repGPC-DM-eVLP appeared to induce better binding antibody titers than all other variants tested at the 10 µg dose (repGPC-WT = 0.029, repGPC-DM = 0.001, repGPC-WT-eVLP = 0.006), with no significant differences at the 1 µg dose. Notably, mice receiving 10 µg of repGPC-DM-eVLP demonstrated significantly higher (p = 0.006) binding titers than mice receiving 10 µg of repGPC-WT-eVLP (Fig. 6B). At day 49, the repGPC-DM-eVLP construct continued to outperform all tested GPC variants, with higher binding antibody titers (repGPC-WT <0.0001, repGPC-DM = <0.0001, repGPC-WT-eVLP = 0.0009) at the 10 µg dose, but with no significant differences at the 1µg dose, except for inferior responses with repGPC-DM (p = 0.0416). | |||||||||||||||||||||
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| DOI: | 10.21430/M3AAL4S28B | |||||||||||||||||||||
| Subjects: | 110 | |||||||||||||||||||||
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| SDY3449: Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques | |||||||
| Status: | New | ||||||
| Description: | The authors assess whether cynomolgus macaques can recapitulate responses to the influenza virus as observed in humans. | ||||||
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| DOI: | 10.21430/M3E21MYU64 | ||||||
| Subjects: | 4 | ||||||
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| SDY3451: Obese individuals show gene expression changes over time after influenza vaccination | ||||||||||
| Status: | New | |||||||||
| Description: | Analysis of changes in gene expression over time and how co-morbidities such as obesity impact the immune response to the seasonal influenza vaccine. Gene expression from whole blood collected from 163 vaccinated human subjects on days 3, 7, and 28 post-vaccination was studied using methods such as HAI assay, library preparation and sequencing, data processing, differential expression analysis, clustering and enrichment, and cell type deconvolution. | |||||||||
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| DOI: | 10.21430/M3ORBFJ9JJ | |||||||||
| Subjects: | 0 | |||||||||
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| SDY3453: Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derive | |||||||||||||
| Status: | New | ||||||||||||
| Description: | This cross-sectional study examined the transcriptional and functional impact of maternal SARS-CoV-2 infection on fetal Hofbauer cells (HBCs) and their potential utility as surrogates for fetal microglial programming. We enrolled 24 pregnant individuals delivering at Massachusetts General Hospital between March 2021 and June 2023: 10 with confirmed SARS-CoV-2 infection during pregnancy (median 12.2 weeks prior to delivery, unvaccinated) and 14 matched controls with no infection history. HBCs were isolated from term placentas using Percoll gradient separation and negative immunoselection (anti-EGFR, anti-CD10), yielding 31,719 high-quality cells for 10x Genomics single-cell RNA sequencing. We identified 8 fetal HBC subclusters (distinguished from maternal PAMMs using sex-chromosome markers DDX3Y/XIST in male placentas, N=10) with distinct baseline transcriptional programs including pro-inflammatory (HBC 3,4,7), stress response (HBC 0,1), tissue repair (HBC 2), and protein processing (HBC 6) phenotypes. Differential gene expression analysis revealed cluster-specific SARS-CoV-2 effects, with HBC 1 (723 DEGs) and HBC 5 (566 DEGs) most affected by number of DEGs, showing altered phagocytosis pathways and enrichment of neuroinflammation-associated signatures. Using direct cytokine reprogramming (IL-34, GM-CSF), we transdifferentiated HBCs into microglia-like cells (HBC-iMGs) expressing IBA1, TMEM119, P2RY12, PU.1, and CX3CR1. Functional phagocytosis assays using pHrodo Red-labeled synaptosomes from iPSC-derived neurons demonstrated significantly reduced phagocytic index in SARS-CoV-2�exposed HBC-iMGs (N=10) versus controls (N=9), with preserved cellular morphology (solidity, eccentricity). These findings establish proof-of-concept for using patient-specific HBC-iMGs as personalized models of fetal microglial programming following maternal immune activation. | ||||||||||||
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| DOI: | 10.21430/M3KQHPU8ND | ||||||||||||
| Subjects: | 24 | ||||||||||||
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| SDY3454: ScRNAseq reveals allergen-specific signatures in human gdT cells | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | In this study, we defined the immune signatures of allergen-reactive gdT cells responding to common allergens, cockroach (CR) and mouse (MO), using sc RNA sequencing (scRNAseq) and a novel Activation-Induced Marker (AIM) flow cytometry assay to provide a high-resolution map of the transcriptional landscapes of gdT cells. While CR extract activated both Vd1 and Vd2 subsets, MO extract primarily stimulated Vd2 cells. Our analysis revealed allergen-specific clusters with distinct functional signatures, including enhanced inflammatory responses and cytotoxic effector functions in MO-specific gdT cells and natural killer cell-mediated immunity and IFNg signaling in CR-specific populations. Comparison of allergic and non-allergic individuals highlighted differences in gene expression and TCR repertoires, including a higher IFNG expression in the CR-allergic compared to non-allergic cohorts, suggesting that phenotypic and functional differences are associated with gdT allergen responses. | |||||||||||||||
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| DOI: | 10.21430/M3TT705GET | |||||||||||||||
| Subjects: | 53 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
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| SDY3456: Analysis of humoral and memory B-cell responses reveals distinct immune landscapes shaped by influenza vaccine | ||||||||||
| Status: | New | |||||||||
| Description: | Evaluation of humoral and cellular immune responses in 33 healthy adults vaccinated with one of the three trivalent seasonal influenza vaccines: Fluzone standard dose vaccine , FluBlock recombinant protein-based vaccine, or FluMist live-attenuated intranasal vaccine. The humoral response was assessed by HAI at day 0 (D0) and 28 days (D28) after vaccination. Flow Cytometry was performed to determine HA-specific memory B-cell response prior to vaccination (D0) and 28 days (D28) post vaccination. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3LGF3R5WB | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
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| SDY3457: Intranasal influenza virus vaccine with TLR agonists | ||||||||||
| Status: | New | |||||||||
| Description: | To address vaccine distribution challenges, thin-film freezing (TFF) process was used to freeze-dry next generation influenza vaccines for shelf-stable storage. The Y2 and NG2 sHA proteins were formulated with either the CpG-1826, INI-4001, or INI-2004 adjuvant, and each vaccine/adjuvant formulation was freeze-dried using the TFF process. Each TFF vaccine/adjuvant dry powder was reconstituted into an aqueous phase and administered intranasally to ferrets to assess antibody responses and protection against influenza virus challenge. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3WC1HSAEW | |||||||||
| Subjects: | 0 | |||||||||
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| Publications: | None | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| Release Notes: |
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| SDY3460: Persistence of a Proteomic Signature After a Hypertensive Disorder of Pregnancy | ||||||||||
| Status: | New | |||||||||
| Description: | A hypertensive disorder of pregnancy is associated with a higher risk of cardiovascular disease later in life, but the potential mechanistic links are unknown. By studying pregnancy and mid-life cohorts, it was found that differences in protein expression persist for years after a hypertensive disorder of pregnancy. The consistent differences in the complement and coagulation pathways may contribute to the increased risk of later life cardiovascular disease. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3LLP8LST1 | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| Release Notes: |
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Updated Studies
| SDY2998: CD4 T cell response to FluBlok adjuvanted with R-DOTAP | |||||||
| Status: | Updated | ||||||
| Description: | Healthy mice were vaccinated with a fifteen-mer influenza peptide adjuvanted FluBlok or AddaVax vaccine. Post-vaccination sera samples from the mice were collected and analyzed for antigen and immune response to the vaccinations using EliSpot assays and flow cytometry. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3OVHA29Y9 | ||||||
| Subjects: | 121 | ||||||
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| Clinical Assessments: | None | ||||||
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| SDY3090: PDI-TCR reveals the dynamics and phenotypes of CD4 T cells in tuberculosis | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Identifying antigen specificity in T cell receptor (TCR) sequences is challenging because of the diversity of the TCR repertoire and the complexity of TCR:antigen recognition. We developed the Peptide-Driven Identification of TCRs (PDI-TCR) assay, which combines in vitro cell expansion with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. PDI-TCR can differentiate true antigen-specific TCR clonotypes from TCRs linked to nonspecific bystander activation by comparing responses to non-overlapping peptide pools. We applied PDI-TCR to Tuberculosis (TB) patients, sampling blood at diagnosis and during treatment, as well as to Mycobacterium tuberculosis (Mtb)-sensitized healthy individuals (IGRA+). Mtb-specific T cells exhibited high diversity, with short-lived effector phenotypes only present in TB at diagnosis, while memory phenotypes were sustained throughout treatment. In contrast, expanded nonspecific T cells were more clonally restricted, displayed a cytotoxic phenotype, and persisted during treatment. | |||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M35YWYAEUK | |||||||||||||||
| Subjects: | 65 | |||||||||||||||
| Study PI, contact: |
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| Clinical Assessments: | None | |||||||||||||||
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| SDY3153: Single Cell Transcriptomics and Immune Profiling in Cutaneous Lyme Disease | |||||||||
| Status: | Updated | ||||||||
| Description: | The skin lesion erythema migrans (EM) is the first clinical sign of Lyme disease, an infection due to the tick-transmitted bacterium Borrelia burgdorferi (Bb). Previously we used single cell transcriptomics with B cell and T cell receptor sequencing to characterize the cutaneous immune response in the EM lesion, focusing on B cells. Here, in an expanded sample size, we profiled T cell responses in the EM lesions in comparison to autologous uninvolved skin. In addition to CD4+IFNG+ T cell subsets known to be abundant in the EM, we identified clonal expansion of CD8+GZMK+IFNG+ T cells that comprised the only T cell population with significant differential expression of interferon regulated genes. This subset included IFNG+ cells with low cytotoxic gene expression, which may promote inflammation. While FOXP3+ regulatory T cells also were increased in EM, we found that the CD4+FOXP3- effector T cell subset contained cells with the highest differential expression of IL-10. Fibroblasts, endothelial cells, and pericytes expressed a broader array of chemokines than macrophages. These studies represent the first comprehensive interrogation of the cutaneous T cell response to Bb infection using single cell transcriptomics and provide insight into the orchestration of the skin immune response to this vector-borne pathogen. |
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| Program/Contract: |
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| DOI: | 10.21430/M365I7LZQU | ||||||||
| Subjects: | 7 | ||||||||
| Study PI, contact: |
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| Publications: | None | ||||||||
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| Clinical Assessments: | None | ||||||||
| Release Notes: |
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| SDY3368: Protection against influenza in young and elderly ferrets by adjuvanted influenza vaccine | |||||||
| Status: | Updated | ||||||
| Description: | To address these age-associated limitations in immune responsiveness, we evaluated Infectimune adjuvanted COBRA hemagglutinin (HA) recombinant vaccines in young (9 months) and elderly (50 to 71 months) ferrets with pre-existing immunity to historical influenza viruses A/Singapore/1986 (H1N1) and A/Panama/1999 (H3N2). Following vaccination, all ferrets were challenged with an A(H1N1) influenza virus A/Brisbane/2018 to determine the degree of protection conferred by the vaccines. Immune responses were analyzed by hemagglutination inhibition assay, influenza viral plaque assay, and enzyme-linked immunosorbent assay. There was an overall enhanced protective antibodies in adjuvant-vaccinated elderly ferrets. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3U51ZJT1Q | ||||||
| Subjects: | 0 | ||||||
| Study PI, contact: |
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| Release Notes: |
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