DR53.1 DataRelease
Release Date: October 2024
New Studies: 26
Updated Studies: 5
New Studies
| SDY2165: Ex vivo Dendritic Cells Treated with Vaccine Strains | |||||||
| Status: | New | ||||||
| Description: | Ex vivo DCs from healthy donors were treated with Vaccine Dengue Strains, Luminex was used to measure inflammatory proteins. | ||||||
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| DOI: | 10.21430/M3WC42X73X | ||||||
| Subjects: | 20 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2188: Maintenance and residence of immune memory to COVID-19 vaccines in tissues | |||||||||||
| Status: | New | ||||||||||
| Description: | Vaccines for COVID-19 establish protection through the generation of pathogen-specific antibodies in circulation, but whether cellular stores of memory are maintained in tissues is unclear. Here, we define the localization, phenotype, function, and tissue residency of memory T and B cells generated to COVID-19 mRNA vaccines across blood, lymphoid organs, and lungs from 33 vaccinated organ donors aged 23-82, of whom 50% were previously infected with SARS-CoV-2. We reveal that in all vaccinated donors, Spike (S)-specific memory T cells distribute across multiple sites though most frequently in lymphoid organs and variably express tissue resident markers based on site and infection history. S-reactive memory B cells are mostly localized to lymphoid sites where they exhibit resident phenotypes in all donors. Importantly, tissue-localized memory populations are more stably maintained post-vaccination and over age than circulating populations. Our results show that mRNA vaccines induce durable tissue-localized memory with the potential for robust protection. | ||||||||||
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| DOI: | 10.21430/M3ANYY64LW | ||||||||||
| Subjects: | 107 | ||||||||||
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| Publications: | None | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY2511: Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and >20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms. Predictive models revealed that IgG binding and ACE2 binding inhibition responses at 1 MPE were positively and C1q complement activity at enrollment was negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE. Serological antibody measures were more predictive than demographic variables of intubation or death among COVID-19 patients. | ||||||||||||||||||
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| DOI: | 10.21430/M3Q2J8C4ER | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Assays: | None | ||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||
| SDY2672: Covid-19 vaccine responses in autoimmune patients | |||||||
| Status: | New | ||||||
| Description: | Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti–spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell–depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti–spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti–type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2–related deaths suggest that T cell immunity contributes to protection in autoimmune disease. | ||||||
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| DOI: | 10.21430/M31L99NVOP | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2757: Infection Recovery in SARS-CoV-2 | |||||||
| Status: | New | ||||||
| Description: | Immune profiling of peripheral blood samples collected at multiple time points, associated with clinical symptom data. | ||||||
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| DOI: | 10.21430/M3DJUSUGA0 | ||||||
| Subjects: | 162 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2763: Noninvasive Biomarker Discovery for Bronchopulmonary Dysplasia (BPD) | |||||||
| Status: | New | ||||||
| Description: | Objective: To determine if oral secretions (OS) can be used in lieu of tracheal aspirates (TA), as a non-invasively collected body fluid, to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. Study Design: This was a retrospective, single-center cohort study that included data and convenience samples from week-of-life (WoL) 3 from two independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatology Intensive Care Unit (NICU) (Cohort 1; N=23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; N=17 infants including 8 with BPD). Results: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (e.g., SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. Conclusion: OS is a noninvasive, easily accessible alternative to TA, that is amenable to high-throughput proteomic analysis in preterm newborns. Additionally, OS samples can yield actionable biomarkers of BPD development and allow for timely, individualized treatment of at-risk infants. | ||||||
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| DOI: | 10.21430/M309C3C6FP | ||||||
| Subjects: | 0 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2780: Association between human leukocyte antigen alleles and endocrine disorders in Russian population | |||||||
| Status: | New | ||||||
| Description: | Endocrine system disorders represent a significant public health concern and can be attributed to negative genetic alterations in individual genes, the combined effects of multiple changes, as well as environmental and lifestyle factors. It is essential to be able to anticipate the risk of endocrine disorders prior to their manifestation. In this research, we investigated the relationship between human leukocyte antigen (HLA) genes and the 13 endocrinopathies. HLA typing was performed on a novel Russian sample from The National Medical Research Center for Endocrinology, Moscow, Russia, with a total of 810 patients. We identified 45 statistically significant associations between HLA alleles and the development of specific disorders, of which 33 are described for the first time and 12 were previously described for type 1 diabetes. Additionally, the inherited pattern of the identified alleles was assessed within the context of their respective diagnoses. As a result, 17 alleles were linked to type 1 diabetes, four were linked to other forms of diabetes, many of which have been well-studied previously. There were also three alleles associated with obesity, five with adrenogenital diseases, three with hypoglycemia, and three with precocious puberty. In addition, there were single alleles linked to congenital hypothyroidism without goiter, hyperfunction of pituitary gland, adrenomedullary hyperfunction, short stature due to endocrine disorder. The study suggests that early human leukocyte antigen (HLA) typing may help identify these conditions at an earlier stage or prevent their occurrence. | ||||||
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| DOI: | 10.21430/M38T5HBVRL | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2812: CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections | |||||||
| Status: | New | ||||||
| Description: | Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious-disease related birth defects worldwide. How the immune response regulates the intrauterine transmission of HCMV after primary maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread through the tissue, but immune responses to infection can also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+ and CD8+ T cells in a guinea pig model of primary CMV infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non-pregnant and pregnant guinea pigs. CD4+ T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital CMV infection. CD8+ T cell depletion was comparably well-tolerated and did not significantly affect guinea pig weights or viral loads in the blood or tissue of adults. However, significantly higher levels of GPCMV infection were observed in the placenta and decidua of CD8+ T cell depleted dams. This study corroborates earlier findings made in nonhuman primates that maternal CD4+ T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also suggesting that other innate and adaptive immune responses can compensate for an abnormal CD8+ T cell response in anti-CD8-treated guinea pigs. | ||||||
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| DOI: | 10.21430/M3M5UV7MC9 | ||||||
| Subjects: | 54 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2824: SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals | ||||||||||
| Status: | New | |||||||||
| Description: | Here we analyze paired serum and saliva samples from patients with and without prior coronavirus disease 2019 (COVID-19) at multiple time points pre and post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination | |||||||||
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| DOI: | 10.21430/M3C3RLCVLT | |||||||||
| Subjects: | 29 | |||||||||
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| SDY2825: Neutralizing Ab SARS-CoV-2 | ||||||||||
| Status: | New | |||||||||
| Description: | COVID mRNA vaccination elicits neutralizing antibodies | |||||||||
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| DOI: | 10.21430/M3FY4IW7EY | |||||||||
| Subjects: | 34 | |||||||||
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| SDY2826: Crossreactive Ab SARSCoV2 | |||||||||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||||||||
| Description: | COVID mRNA vaccination using mAb Therapy | ||||||||||||||||||||||||||||
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| DOI: | 10.21430/M35389OBXZ | ||||||||||||||||||||||||||||
| Subjects: | 28 | ||||||||||||||||||||||||||||
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| SDY2827: Characterization of non-neutralizing human monoclonal antibodies that target the M1 and NP of influenza A viruses | |||||||||
| Status: | New | ||||||||
| Description: | The authors characterize six human monoclonal antibodies isolated from two H3N2-infected donors that showed robust binding against the conserved internal nucleoprotein or matrix protein 1 influenza A virus strains. | ||||||||
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| DOI: | 10.21430/M33LLW8CHV | ||||||||
| Subjects: | 82 | ||||||||
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| SDY2830: Antibody Responses to HA and NA vaccines | |||||||
| Status: | New | ||||||
| Description: | The study was conducted using a mouse model to assess the antibody response to COBRA vaccines combined with different adjuvants. The vaccines tested were HA-based H1 COBRA, Y2, and an NA-based N1 COBRA, N1-I and adjuvants were AddaVax, AddaS03, CpG, and Alhydrogel. | ||||||
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| DOI: | 10.21430/M3HA37XHVE | ||||||
| Subjects: | 200 | ||||||
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| Assays: | None | ||||||
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| SDY2837: Identification of a Broadly Protective Seasonal Influenza Vaccination-induced Neuraminidase Antibody | ||||||||||
| Status: | New | |||||||||
| Description: | This study explored the potential use of NA as an immunogen for next-generation influenza vaccines by characterizing a vaccine-induced broadly protective monoclonal antibody (mAb) targeting NA. | |||||||||
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| DOI: | 10.21430/M3JTB2XOM2 | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2838: Binding and Avidity Signatures of Polyclonal Sera From Individuals With Different Exposure Histories to Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Vaccination, and Omicron Breakthrough Infections. | |||||||
| Status: | New | ||||||
| Description: | Here, the investigators explored how different exposures to SARS-CoV-2 infection or vaccination influence the polyclonal immune response. | ||||||
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| DOI: | 10.21430/M3X11RM5CN | ||||||
| Subjects: | 105 | ||||||
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| SDY2839: Advax adjuvanted COBRA vaccines | |||||||
| Status: | New | ||||||
| Description: | Evaluate the immune response induced by Advax-SM adjuvant in combination with broadly reactive influenza hemagglutinin (HA) vaccines in mouse model and to investigate how these responses elicit the most protective immune responses against H1N1 and H3N2 influenza viruses. | ||||||
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| DOI: | 10.21430/M3UD76FFV9 | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY2840: Development of Influenza vaccine adjuvanted with mastoparan-7 and CpG | |||||||
| Status: | New | ||||||
| Description: | The adjuvant system Mastoparan7-CpG was co-administered with COBRA HA protein in a mouse model. Humoral, cellular and protective responses were evaluated against different Influenza strains. | ||||||
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| DOI: | 10.21430/M3PS9SYU8N | ||||||
| Subjects: | 103 | ||||||
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| SDY2843: The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera | ||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||
| Description: | As demonstrated by severe acute respiratory syndrome coronavirus 2, coronaviruses pose a significant pandemic threat. Here, we show that coronavirus disease 2019 mRNA vaccination can induce significant levels of cross-reactive antibodies against diverse coronavirus spike proteins. While these antibodies are binding antibodies that likely have little neutralization capacity and while their contribution to cross-protection is unclear, it is possible that they may play a role in protection from progression to severe disease with novel coronaviruses. | |||||||||||||||||||||
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| DOI: | 10.21430/M3WAAJNDC9 | |||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||
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| SDY2844: Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers | |||||||||||||
| Status: | New | ||||||||||||
| Description: | We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses. | ||||||||||||
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| DOI: | 10.21430/M365ZO30EV | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| SDY2845: Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses | |||||||||
| Status: | New | ||||||||
| Description: | Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza. | ||||||||
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| DOI: | 10.21430/M3ECEGE6PK | ||||||||
| Subjects: | 0 | ||||||||
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| SDY2846: Inefficient Induction of Neutralizing Antibodies against SARS-CoV-2 Variants in Patients with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy after Receiving a Third mRNA Vaccine Dose | |||||||
| Status: | New | ||||||
| Description: | Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose can neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)]. Fifty-six subjects with IBD and 12 healthy subjects were recruited. Ninety percent of patients with IBD (49/56) received biologics and/or immunomodulatory therapy. Twenty-four subjects with IBD did not develop effective neutralizing capability against the Omicron variant. Seventy percent (17/24) of those subjects received anti-tumor necrosis factor therapy [10 = adalimumab, 7 = infliximab], two of which had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and more extensive studies are needed to evaluate optimal immunity. | ||||||
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| DOI: | 10.21430/M35E2CXA58 | ||||||
| Subjects: | 0 | ||||||
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| SDY2847: SARS-CoV-2 variants evolve convergent strategies to remodel the host response | |||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||
| Description: | SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics. | ||||||||||||||||||||||
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| DOI: | 10.21430/M39QFRIL9A | ||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||
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| SDY2848: Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice | |||||||||||||
| Status: | New | ||||||||||||
| Description: | The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera. | ||||||||||||
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| DOI: | 10.21430/M3CKWIFP8M | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| SDY2849: Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 and Other Coronaviruses, December 2019 to July 2020 | |||||||||||
| Status: | New | ||||||||||
| Description: | Background: The first coronavirus disease 2019 (COVID-19) case in the United States was recognized on 19 January 2020, but the time of introduction of the virus into the United States is unknown. An existing sample cohort was examined for serologic evidence of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Methods: A repository of 46 120 samples from healthy routine blood donors, representing 46 states and the District of Columbia, was tested for total antibodies to SARS-CoV-2 nucleocapsid (anti-N) using a commercial test. All reactive samples were further tested using an experimental receptor-binding domain (RBD)-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Further testing was also conducted for anti-spike (anti-S) antibodies by commercial tests, experimental anti-S immunologic blocking, and for antibodies to the 4 human cold coronaviruses. Results: Anti-N reactivity was observed in 92 tested samples (0.2%), 91 of which had adequate volume for further testing; of these, 55 were confirmed positive by anti-RBD. None of these reactive findings were attributable to the other human coronaviruses tested. The confirmed-positive frequency increased over time paralleling patterns observed for COVID-19 cases reported in the United States (in contrast to stable patterns over time for the cold coronaviruses). Nine confirmed positive samples (0.07%) were identified among the 13 364 donations collected between 13 December 2019 and 22 January 2020. None of these early confirmed-positive samples were reactive by commercial anti-S tests suggesting very recent infection. Conclusions: The samples tested in this study were broadly representative of the United States, and all were from individuals who had successfully donated blood. The antibody-reactive results of this study suggest that SARS-CoV-2 was likely present in the United States before 19 January 2020. | ||||||||||
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| DOI: | 10.21430/M3E089K5BJ | ||||||||||
| Subjects: | 0 | ||||||||||
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| SDY2850: Neutralization and binding antibody response to second bivalent COVID-19 vaccination in nursing home residents | |||||||||||||
| Status: | New | ||||||||||||
| Description: | To date, SARS-CoV-2 has infected more than 1.6 million U.S. nursing home (NH) residents and killed more than 160,000.1 Vaccination plays a vital role in preventing SARS-CoV-2 infection and reducing morbidity and mortality burden in this population. A single bivalent COVID-19 mRNA vaccine broadens SARS-CoV-2 immunity and reduces infection, hospitalization, and death beyond that from monovalent vaccination. We extend our work here by evaluating the immune response following a second bivalent vaccine dose. | ||||||||||||
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| DOI: | 10.21430/M3KY3HL3MU | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2856: Mode of Delivery Predicts Postpartum Maternal Leukocyte Telomere Length | |||||||
| Status: | New | ||||||
| Description: | Background: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging. Study design: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma). Results: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p =0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta − 496.1, 95 % confidence interval [CI] − 891.1, − 101.1, p =0.01) and beyond (adjusted beta − 396.8; 95 % CI − 727.2, − 66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction. Conclusion: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted. | ||||||
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| DOI: | 10.21430/M3SBBP9K9I | ||||||
| Subjects: | 0 | ||||||
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Updated Studies
| SDY1909: Study to Evaluate Safety, Immunogenicity and Efficacy of PfSPZ Vaccine in HIV Negative and HIV Positive Tanzanian Adults (BSPZV3a) | ||||||||||
| Status: | Updated | |||||||||
| Description: | This trial is a single center trial designed to assess the safety, tolerability, immunogenicity and efficacy of PfSPZ Vaccine (9.0x10^5 PfSPZ given at 0, +2, +4, +6 and +28 days (Group 1, HIV negative, and Group 2, HIV positive)). Controls will receive parallel injections with normal saline (NS). All administrations of PfSPZ or NS will be by direct venous inoculation (DVI). Twenty-one male and female adult volunteers, aged from 18 to 45 years, who live in and around the Bagamoyo township, will be enrolled based on pre-defined inclusion and exclusion criteria. 12/21 subjects will be HIV positive volunteers (who clinical stage 1) on stable anti-retroviral therapy (ART) for at least 3 months with a CD4+ cell count above 500 cells/_L at screening. The rest (9/21) will be healthy HIV negative adults. Treatment allocation will be double-blind within Group 1 and 2b but not between the groups or subgroups. Immunizations will begin with healthy HIV negative volunteers first (Group 1), before inoculation of HIV positive volunteers (Groups 2a and 2b). Transitioning from immunization of HIV negative to immunization of HIV positive will begin by immunizing a sentinel group of 3 HIV positive individuals with a reduced vaccine dose of 4.5x10^5 PfSPZ (Group 2a). This transition will be staggered by at least two (2) weeks, to allow for a safety data review. If the safety data do not meet pause criteria, this will signal a ""go"" for transitioning to immunizations of sentinel group of three (3) HIV positive volunteers. If pause criteria are met, there will be no immediate transition, and instead an ad-hoc meeting of the Safety Monitoring Committee (SMC) will be called for an independent review and recommendation. Transition from the unblinded HIV positive sentinel Group 2a to the full study cohort of double blinded placebo controlled HIV positive volunteers (Group 2b), will also be staggered for at least two (2) weeks. There will be a scheduled review by the SMC of safety data collected from the sentinel HIV positive group for up to 7 days after the fourth immunization. After the safety review, transition to the main HIV positive group (Group 2b) will take into account the SMC recommendation(s). | |||||||||
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| DOI: | 10.21430/M3D8HU5M98 | |||||||||
| Subjects: | 21 | |||||||||
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| SDY2213: Drivers of Heterogeneity in Synovial Fibroblasts in Rheumatoid Arthritis. | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Rheumatoid arthritis (RA), a systemic autoimmune disease with predominantly articular manifestations, is characterized by hyperplasia of both the synovial lining, which interfaces the synovial fluid-filled joint space, as well as the synovial sublining, which exhibits increased vascularization and an influx of leukocytes. Both the lining and sublining fibroblast-like synoviocytes (FLS) undergo proliferation and activation, assuming states in which they stimulate angiogenesis, produce pro-inflammatory cytokines and chemokines, and invade adjacent articular cartilage and bone. Expression of MHC class II molecules by activated FLS is associated with synovial inflammation and correlates with disease activity4. HLA-DR+ FLS expression of soluble mediators, including the proinflammatory cytokines IL-6 and IL-15, and chemokines CCL2, CXCL9, and CXCL12 along with adhesion molecules such as ICAM1 and VCAM1 suggests that these features of FLS might be imparted by their interactions with leukocytes. In support of this possibility, prior in vitro studies have shown that HLA-DR+ FLS are capable of presenting antigens to CD4+ T cells. Furthermore, production of the aforementioned proinflammatory chemokines by FLS likely acts as a feedforward mechanism to further facilitate recruitment of diverse immune cell types expressing the corresponding receptors. Indeed, recent studies of the overall cellular makeup of synovial tissue from RA patients using single cell RNA sequencing (scRNA-seq) analysis identified a diverse mix of migratory and resident cell types of hematopoietic and non-hematopoietic origin including different CD4+ and CD8+ T cell subsets, myeloid cells, and FLS. These observations suggest that states of FLS activation in the RA synovium are likely driven by a diversity of infiltrating innate and adaptive immune cell and that this modulation ultimately impacts disease pathogenesis. Thus, we sought to undertake an in-depth investigation of the spectrum of FLS states in the inflamed RA synovium as well as the drivers underlying the observed heterogeneity through paired scRNA and assay for transposase-accessible chromatin with sequencing (scRNA/ATAC-seq) and in vitro modeling of FLS transcriptional responses to key immune cell-derived proinflammatory cytokines. We then mapped the spatial distribution of FLS heterogeneity and transcriptional responses by employing spatial transcriptomic (ST) analyses and multiplex imaging. Our findings suggest that spatially constrained FLS responses to three leukocyte-derived cytokines, TNFα, IFNγ, and IL-1β, or lack thereof, drive the formation of four distinct FLS states found in the inflamed RA synovium. | ||||||||||||
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| DOI: | 10.21430/M3M8AX1TI9 | ||||||||||||
| Subjects: | 6 | ||||||||||||
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| Publications: | None | ||||||||||||
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| SDY2393: Rhesus H-ARS Dose-Response Relationship | |||||||
| Status: | Updated | ||||||
| Description: | Rhesus macaques (Macaca mulatta) were exposed to total-body irradiation ranging from 500 cGy to 750 cGy at a dose rate of 50 cGy/min from a Co-60 source and were observed for 60 days for mortality and clinical signs. Each group consisted of 4 males and 4 females. Animals were provided with supportive care which included antibiotics, fluids, anti-ulcer, anti-emetics, analgesics, nutritional support, and wound disinfection administered according to pre-determined criteria, but were not provided blood transfusions. Blood was drawn at predetermined time points and blood cells were counted. Note: Day 1 is 24 hours after the day of irradiation, which is designated in the data files as Day -1. There is no Day 0. Keywords: rhesus macaques, radiation, natural history, radiation sickness, hematopoietic, hematology, proteomics, metabolomics | ||||||
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| DOI: | 10.21430/M3ZAEP8Q6S | ||||||
| Subjects: | 48 | ||||||
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| SDY2412: The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera | ||||||||||
| Status: | Updated | |||||||||
| Description: | Here, the investigators report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly cross-reactive binding antibodies to spikes from a wide range of coronaviruses. | |||||||||
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| DOI: | 10.21430/M3YZAEH2H6 | |||||||||
| Subjects: | 118 | |||||||||
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| SDY2540: Multi-modal data integration using Markov Field graphical networks predicts B cell depletion and immune responses associated with protective intravenous BCG (IV-BCG) vaccination against tuberculosis in macaques | |||||||
| Status: | Updated | ||||||
| Description: | Multi-modal biological datasets provide rich information from different scales or aspects of complex biological systems that can be analyzed to highlight the critical multi-scale interactions underlying specific biological phenomena. However, identifying the strongest associations between features and desired outputs can be beset by a high degree of intra-dataset correlation and spurious connections due to indirect impacts of multiple immune features propagating through an unmapped biological network. Here, we applied a probabilistic graphical modeling approach, Markov Fields, to empirically dissect correlations between all features from a public multi-modal dataset (antibody titers, antibody-dependent functions, cytokines, cytometry) from macaques undergoing intravenous BCG vaccination—a promising vaccine strategy against the major public health threat tuberculosis. This yielded an interaction network that interprets the collection of multi-scale paths by which vaccine effects propagate through the immune network to eventually protect against tuberculosis infection. Importantly, the models shows that the vast majority of correlations between features arise indirectly due to multiple interactions connecting distant immune features to each other. We next conducted experimental depletion of B cells during BCG IV vaccination in macaques--which did not reduce BCG IV-mediated protection against tuberculosis—and validated that our Markov Field models can predict subtle systems-wide shifts across the immune system in response to this perturbation. Finally, we also apply our model to highlight immune changes in the network that are predicted to have strong effects on IV-BCG efficacy, showing that probabilistic graphical models increase the interpretability and value of multi-scale datasets for identifying new targets in disease. | ||||||
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| DOI: | 10.21430/M38IT61DK0 | ||||||
| Subjects: | 0 | ||||||
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