DR55 DataRelease
Release Date: March 2025
New Studies: 34
Updated Studies: 54
New Studies
| SDY2394: Human in vitro modeling of adjuvants | |||||||
| Status: | New | ||||||
| Description: | Characterization of cellular and molecular activity of adjuvant formulations using four complementary human in vitro platforms to assess individual and combined adjuvants in unformulated, oil-in-water, and liposomal delivery platforms. | ||||||
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| DOI: | 10.21430/M3X8FTKTPF | ||||||
| Subjects: | 5 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2766: CD8+ TEMRAs in Asthma | ||||||||||
| Status: | New | |||||||||
| Description: | Aberrant immune response is a hallmark of asthma, with 5-10% of patients suffering from disease. A better understanding of the immune response contributing to disease heterogeneity is critical for improving asthma management. T cells are central in the orchestration of immune responses in both mild and severe asthma, but it is unclear whether specific T cell subsets influence asthma symptoms or severity. This study evaluated whether specific T cell subsets including CD8+ effector memory T cells re-expressing CD45RA (TEMRAs) associated with disease severity. We performed flow cytometric immunophenotyping on PBMCs obtained from healthy controls and patients with either mild to moderate or severe asthma. Evaluation included expression of surface markers of senescence, cytokine secretion, and proliferation assays. | |||||||||
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| DOI: | 10.21430/M3L7ZINF2A | |||||||||
| Subjects: | 55 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2820: Comparable Non-canonical T cell responses are associated with protection from tuberculosis in mice and humans | |||||||
| Status: | New | ||||||
| Description: | While control of Mycobacterium tuberculosis (Mtb) infection is generally understood to require a Th1-immune response and IFN secretion, infection produces a spectrum of immunological and pathological phenotypes in diverse human populations. By characterizing Mtb infection in a collection of mouse strains that models the genetic heterogeneity of an outbred population, we identified a subset of strains that control Mtb burden comparably to a standard IFN-dependent mouse model but with substantially lower lung IFN levels. Here we report that these mice have significantly fewer Th1 and more Th17 and regulatory T cells and that this phenotype is detectable before infection, indicating a general alteration in immune tone. The CD4 T cells are less activated, have a lower polyfunctionality score, and are specifically lacking the terminal effector Th1 subset. These mice still require T cells to control bacterial burden but are less dependent on IFN signaling for this function. Instead, non-canonical immune features such as CD4 Th17 and T cells correlate with low bacterial burden. We find that the same Th17 transcriptional programs in CD4 T cells are associated with resistance to Mtb infection in humans, implicating specific non-Th1 T cell responses as a common feature of Mtb control across species. | ||||||
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| DOI: | 10.21430/M3X0OC3UP1 | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2930: Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 | |||||||
| Status: | New | ||||||
| Description: | The study employs single-cell multi-omics analysis to extensively profile the immune responses in hospitalized COVID-19 patients, aiming to identify the specific immune signatures associated with severe, immunopathological reactions. The key finding is a profound dyssynchrony between the innate and adaptive arms of the immune system in patients with progressive COVID-19, characterized by abnormal monocyte and T cell phenotypes, skewed T cell receptor repertoires, and dysregulated interactions between myeloid and T cells. These insights into the immunopathology of COVID-19 could have important implications for the development of targeted immunotherapies. | ||||||
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| DOI: | 10.21430/M3Q5PBRY55 | ||||||
| Subjects: | 10 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2957: Flow Cytometry of IPS Celllines | |||||||
| Status: | New | ||||||
| Description: | MACS purification and flow cytometry analysis were performed as described in | ||||||
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| DOI: | 10.21430/M33LRHRDWW | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2969: COBRA HA and NA vaccines and influenza immune response | |||||||
| Status: | New | ||||||
| Description: | Healthy mice were vaccinated with Z1, IAN8, Q6, N1-I, and N2-B COBRA vaccines formulated with Addavax, then challenged with A/Sichuan/26221/2014 virus. Serologic antibodies, protective efficacy and possible contribution of protection were investigated. | ||||||
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| DOI: | 10.21430/M3YQNDWAWG | ||||||
| Subjects: | 57 | ||||||
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| SDY2970: XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1 | |||||||
| Status: | New | ||||||
| Description: | The authors investigate the immunogenicity of new COVID-19 vaccines that contain the spike protein of the SARS-CoV-2 XBB.1.5 subvariant. | ||||||
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| DOI: | 10.21430/M3F9PC4F3L | ||||||
| Subjects: | 78 | ||||||
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| SDY2971: Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination | ||||||||||
| Status: | New | |||||||||
| Description: | To better model the human immune experience, the investigators introduce additional microbial experiences to specific pathogen-free mice by way of 3 models. | |||||||||
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| DOI: | 10.21430/M3776YV6E7 | |||||||||
| Subjects: | 69 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2973: COBRA Vaccines protect against H5Nx Viral Infections | ||||||||||
| Status: | New | |||||||||
| Description: | Mice were vaccinated with H5 COBRA rHA. The antibody activity against H5Nx viruses was assessed through HAI, plaque assay, and immunohistochemistry staining following vaccination. | |||||||||
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| DOI: | 10.21430/M3GFUYOAKW | |||||||||
| Subjects: | 272 | |||||||||
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| SDY2978: Cell epitope abundance enhances responses to vaccines | ||||||||||
| Status: | New | |||||||||
| Description: | Mice were immunized with HA-Ferritin or HA-trimer; the immunized mice had an increase in antibody cells, along with an increase of CD4 and GC B cell abundance. The increased availability of the CD4 T cells enhanced immunogenicity response to the vaccinations. | |||||||||
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| DOI: | 10.21430/M3P3ZHYLR5 | |||||||||
| Subjects: | 138 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2979: Immunogenicity of adjuvanted COBRA vaccine in immunocompromised and diverse populations | |||||||
| Status: | New | ||||||
| Description: | Evaluation of immunogenicity of adjuvanted broadly active influenza vaccine in mouse model of obesity, aging, and chemotherapy-induced immunosuppression. Vaccine efficacy was examined in a collaborative cross mice, diverse population that mimics human genetic heterogeneity. | ||||||
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| DOI: | 10.21430/M3ALTYN1EY | ||||||
| Subjects: | 222 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2980: Development of Intranasal Gel for Influenza Vaccine Delivery | |||||||
| Status: | New | ||||||
| Description: | Mice were vaccinated with COBRA H1 HA STING cGAMP into a nasal gel against influenza and assessed for immune responses. The intranasal gel led to generation of IgG2 and IgG1. The study suggests the utility of intranasal gel for the delivery of COBRA antigens for the creation of serum and mucosal humoral responses. | ||||||
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| DOI: | 10.21430/M3UQ0AB3PT | ||||||
| Subjects: | 79 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2982: Development of Ferret Reference Resources and Profiling Assays. | ||||||||||
| Status: | New | |||||||||
| Description: | This study designed new ferret-specific immune repertoire profiling assays by targeting positions in constant regions without allelic diversity. Transcriptome sequencing of ferret splenocyte and lymph node samples was perfomed to obtain Ig and T cell receptor transcripts. These improved resources and assays enables further studies to capture ferret immune diversity. | |||||||||
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| DOI: | 10.21430/M3KVP4YEVN | |||||||||
| Subjects: | 29 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2983: Racial disparities in symptomatology and outcomes of COVID-19 among adults of Arkansas | ||||||||||
| Status: | New | |||||||||
| Description: | Few reports have suggested that non-Hispanic (NH) blacks may present with different symptoms for COVID-19 than NH-whites. The objective of this study was to investigate patterns in symptomatology and COVID-19 outcomes by race/ethnicity among adults in Arkansas. Data on COVID-19 symptoms were collected on day of testing, 7th and 14th day among participants at UAMS mobile testing units throughout the state of Arkansas. Diagnosis for SARS-CoV-2 infection was confirmed via nasopharyngeal swab and RT-PCR methods. Data analysis was conducted using Chi-square test and Poisson regression to assess the differences in characteristics by race/ethnicity. A total of 60,648 individuals were RT-PCR tested from March 29, 2020 through October 7, 2020. Among adults testing positive, except shortness of breath, Hispanics were more likely to report all symptoms than NH-whites or NH-blacks. NH-whites were more likely to report fever (19.6% vs. 16.6%), cough (27.5% vs. 26.1%), shortness of breath (13.6% vs. 9.6%), sore throat (16.7% vs. 10.7%), chills (12.5% vs. 11.8%), muscle pain (15.6% vs. 12.4%), and headache (20.3% vs. 17.8%). NH-blacks were more likely to report loss of taste/smell (10.9% vs. 10.6%). To conclude, we found differences in COVID-19 symptoms by race/ethnicity, with NH-blacks and Hispanics more often affected with specific or all symptoms, compared to NH-whites. Due to the cross-sectional study design, these findings do not necessarily reflect biological differences by race/ethnicity; however, they suggest that certain race/ethnicities may have underlying differences in health status that impact COVID-19 outcomes. | |||||||||
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| DOI: | 10.21430/M3V5LZ099V | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2984: SARS-CoV-2 serosurvey across multiple waves of the COVID-19 pandemic in New York City between 2020–2023 | ||||||||||
| Status: | New | |||||||||
| Description: | Sero-monitoring provides context to the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and changes in population immunity following vaccine introduction. Here, we describe results of a cross-sectional hospital-based study of anti-spike seroprevalence in New York City (NYC) from February 2020 to July 2022, and a follow-up period from August 2023 to October 2023. Samples from 55,092 individuals, spanning five epidemiological waves were analyzed. Prevalence ratios (PR) were obtained using Poisson regression. Anti-spike antibody levels increased gradually over the first two waves, with a sharp increase during the 3rd wave coinciding with SARS-CoV-2 vaccination in NYC resulting in seroprevalence levels >90% by July 2022. Our data provide insights into the dynamic changes in immunity occurring in a large and diverse metropolitan community faced with a new viral pathogen and reflects the patterns of antibody responses as the pandemic transitions into an endemic stage. | |||||||||
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| DOI: | 10.21430/M3RPBPG29R | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2985: Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes | |||||||||||||||
| Status: | New | ||||||||||||||
| Description: | It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known. Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses. Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients. | ||||||||||||||
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| DOI: | 10.21430/M3OOXDACLG | ||||||||||||||
| Subjects: | 0 | ||||||||||||||
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| SDY2986: High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines | |||||||
| Status: | New | ||||||
| Description: | Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, we evaluated seroprevalence to the hCoVs, whether pre-pandemic hCoV immunity modulated subsequent risk of SARS-CoV-2 infection, and if SARS-CoV-2 infection affected the transmission of the hCoVs. Methods: From 499 individuals screened in 2021 for SARS-CoV-2 receptor binding domain (RBD) antibodies by enzyme-linked immunosorbent assay (ELISA), we randomly selected 59 SARS-CoV-2 negative and 61 positive individuals for further serological evaluation. We measured RBD and spike antibodies to the four hCoVs and SARS-CoV-2 by ELISA in samples from the same participants collected pre-pandemic (2018-2019) and mid-pandemic (2021), before COVID-19 vaccination. Results: We observed over 72% seropositivity to the four hCoVs pre-pandemic. Binding antibodies increased with age to 229E and OC43, suggesting endemic circulation, while antibody levels was flat across ages for HKU1 and NL63. During the COVID-19 pandemic, antibodies increased significantly to the RBDs of OC43, NL63, and 229E and spikes of all four hCoVs in both SARS-CoV-2 negative and positive adolescents. Those aged 12-15 years old in 2021 had higher antibodies to RBD and spike of OC43, NL63, and 229E than adolescents the same age in 2019, further demonstrating intense transmission of the hCoVs during the pandemic. Conclusions: We observe a limited impact of the COVID-19 pandemic on endemic hCoV transmission. This study provides insight into co-circulation of hCoVs and SARS-CoV-2. | ||||||
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| DOI: | 10.21430/M3YR9AKCII | ||||||
| Subjects: | 0 | ||||||
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| SDY2987: Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seroprevalence in Massachusetts Estimated from Newborn Screening Specimens | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Background: Estimating the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for setting public health policies. We leveraged deidentified Massachusetts newborn screening specimens as an accessible, retrospective source of maternal antibodies for estimating statewide seroprevalence in a nontest-seeking population. Methods: We analyzed 72 117 newborn specimens collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification. Results: Statewide seroprevalence was estimated to be 0.03% (90% credible interval [CI], 0.00-0.11) in November 2019 and rose to 1.47% (90% CI: 1.00-2.13) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onward, reaching 2.15% (90% CI: 1.56-2.98) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = .024; 90% CI: 0.004-0.044); i.e., a 10% increase in community percent non-Hispanic Black was associated with 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter. Conclusions: Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable. | ||||||||||||
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| DOI: | 10.21430/M3FM3P67HT | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| SDY2988: Serologic Response to Messenger RNA Coronavirus Disease 2019 Vaccines in Inflammatory Bowel Disease Patients Receiving Biologic Therapies | |||||||
| Status: | New | ||||||
| Description: | Inflammatory bowel disease (IBD) patients with Crohn’s disease and ulcerative colitis have been considered at increased risk of severe coronavirus disease 2019 (COVID-19) because they are often treated with immunosuppressive medications. Indeed, steroids and thiopurines in combination therapy with tumor necrosis factor (TNF) antagonists, but not TNF antagonist monotherapy, have been associated with a risk of severe COVID-19 in IBD patients. Expert consensus advocates that IBD patients should be vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).3 A study showing attenuated antinucleocapsid responses to SARS-CoV-2 infection in IBD patients on infliximab and another study reporting poor antispike antibody responses in organ transplant patients after the first dose of messenger RNA vaccines have raised concern regarding vaccine responses in IBD patients.4–6 Still, the impact of medications on COVID-19 vaccine efficacy in IBD patients is unknown, because patients with immunosuppressed states and/or treated with immunosuppressants were excluded from vaccine trials. To address this, we evaluated serologic responses to COVID-19 vaccination with the SARS-CoV-2 spike (S) messenger RNA BNT162b2 (Pfizer BioNTech) and messenger RNA-1273 (National Institutes of Health [NIH]-Moderna) vaccines in IBD patients. | ||||||
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| DOI: | 10.21430/M3KO9YAJYY | ||||||
| Subjects: | 0 | ||||||
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| SDY2989: Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not. | |||||||||||||||
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| DOI: | 10.21430/M3RQPL9W9U | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| SDY2990: Predictive power of wastewater for nowcasting infectious disease transmission: A retrospective case study of five sewershed areas in Louisville, Kentucky | |||||||
| Status: | New | ||||||
| Description: | Background: Epidemiological nowcasting traditionally relies on count surveillance data. The availability and quality of such count data may vary over time, limiting representation of true infections. Wastewater data correlates with traditional surveillance data and may provide additional value for nowcasting disease trends. Methods: We obtained SARS-CoV-2 case, death, wastewater, and serosurvey data for Jefferson County, Kentucky (USA), between August 2020 and March 2021, and parameterized an existing nowcasting model using combinations of these data. We assessed the predictive performance and variability at the sewershed level and compared the effects of adding or replacing wastewater data to case and death reports. Findings: Adding wastewater data minimally improved the predictive performance of nowcasts compared to a model fitted to case and death data (Weighted Interval Score (WIS) 0.208 versus 0.223), and reduced the predictive performance compared to a model fitted to deaths data (WIS 0.517 versus 0.500). Adding wastewater data to deaths data improved the nowcasts agreement to estimates from models using cases and deaths data. These findings were consistent across individual sewersheds as well as for models fit to the aggregated total data of 5 sewersheds. Retrospective reconstructions of epidemiological dynamics created using different combinations of data were in general agreement (coverage >75%). Interpretation: These findings show wastewater data may be valuable for infectious disease nowcasting when clinical surveillance data are absent, such as early in a pandemic or in low-resource settings where systematic collection of epidemiologic data is difficult. | ||||||
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| DOI: | 10.21430/M333EBOIW7 | ||||||
| Subjects: | 0 | ||||||
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| SDY2992: Brief research report: impact of vaccination on antibody responses and mortality from severe COVID-19 | ||||||||||
| Status: | New | |||||||||
| Description: | Introduction While it is established that vaccination reduces risk of hospitalization, there is conflicting data on whether it improves outcome among hospitalized COVID-19 patients. This study evaluated clinical outcomes and antibody (Ab) responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection/vaccines in patients with acute respiratory failure (ARF) and various comorbidities. Methods In this single-center study, 152 adult patients were admitted to Ohio State University hospital with ARF (05/2020 – 11/2022) including 112 COVID-19-positive and 40 COVID-19-negative patients. Of the COVID-19 positive patients, 23 were vaccinated for SARS-CoV-2 (Vax), and 89 were not (NVax). Of the NVax COVID-19 patients, 46 were admitted before and 43 after SARS-CoV-2 vaccines were approved. SARS-CoV-2 Ab levels were measured/analyzed based on various demographic and clinical parameters of COVID-19 patients. Additionally, total IgG4 Ab concentrations were compared between the Vax and NVax patients. Results While mortality rates were 36% (n=25) and 27% (n=15) for non-COVID-19 NVax and Vax patients, respectively, in COVID-19 patients mortality rates were 37% (NVax, n=89) and 70% (Vax, n=23). Among COVID-19 patients, mortality rate was significantly higher among Vax vs. NVax patients (p=0.002). The Charlson’s Comorbidity Index score (CCI) was also significantly higher among Vax vs. NVax COVID-19 patients. However, the mortality risk remained significantly higher (p=0.02) when we compared COVID-19 Vax vs. NVax patients with similar CCI score, suggesting that additional factors may increase risk of mortality. Higher levels of SARS-CoV-2 Abs were noted among survivors, suggestive of their protective role. We observed a trend for increased total IgG4 Ab, which promotes immune tolerance, in the Vax vs. NVax patients in week 3. Conclusion Although our cohort size is small, our results suggest that vaccination status of hospital-admitted COVID-19 patients may not be instructive in determining mortality risk. This may reflect that within the general population, those individuals at highest risk for COVID-19 mortality/immune failure are likely to be vaccinated. Importantly, the value of vaccination may be in preventing hospitalization as opposed to stratifying outcome among hospitalized patients, although our data do not address this possibility. Additional research to identify factors predictive of aberrant immunogenic responses to vaccination is warranted. | |||||||||
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| DOI: | 10.21430/M37K8ASSB5 | |||||||||
| Subjects: | 0 | |||||||||
| Study PI, contact: |
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| Assays: |
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| Clinical Assessments: | None | |||||||||
| SDY2993: Identifying beliefs driving COVID-19 vaccination: Lessons for effective messaging | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Increasing vaccination acceptance has been essential during the COVID-19 pandemic and in preparation for future public health emergencies. This study aimed to identify messaging strategies to encourage vaccine uptake by measuring the drivers of COVID-19 vaccination among the general public. A survey to assess COVID-19 vaccination acceptance and hesitancy was advertised on Facebook in February–April 2022. The survey included items asking about COVID-19 vaccination status and participant demographics, and three scales assessing medical mistrust, perceived COVID-19 risk, and COVID-19 vaccine confidence (adapted from the Oxford COVID-19 vaccine confidence and complacency scale). The main outcome was vaccination, predicted by patient demographics and survey scale scores. Of 1,915 survey responses, 1,450 (75.7%) were included, with 1,048 (72.3%) respondents reporting they had been vaccinated. In a multivariable regression model, the COVID-19 vaccine confidence scale was the strongest predictor of vaccination, along with education level and perceived COVID-19 risk. Among the items on this scale, not all were equally important in predicting COVID-19 vaccination. The items that best predicted vaccination, at a given score on the COVID-19 vaccine confidence scale, included confidence that vaccine side effects are minimal, that the vaccine will work, that the vaccine will help the community, and that the vaccine provides freedom to move on with life. This study improved our understanding of perceptions most strongly associated with vaccine acceptance, allowing us to consider how to develop messages that may be particularly effective in encouraging vaccination among the general public for both the COVID-19 pandemic and future public health emergencies. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3HF85QYB5 | ||||||||||||
| Subjects: | 0 | ||||||||||||
| Study PI, contact: |
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| Resources: |
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2994: Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV-2 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Enveloped viruses co-opt host glycosylation pathways to decorate their surface proteins. As viruses evolve, emerging strains can modify their glycosylation patterns to influence host interactions and subvert immune recognition. Still, changes in viral glycosylation or their impact on antibody protection cannot be predicted from genomic sequences alone. Using the highly glycosylated SARS-CoV-2 Spike protein as a model system, we present a lectin fingerprinting method that rapidly reports on changes in variant glycosylation state, which are linked to antibody neutralization. In the presence of antibodies or convalescent and vaccinated patient sera, unique lectin fingerprints emerge that distinguish neutralizing versus non-neutralizing antibodies. This information could not be inferred from direct binding interactions between antibodies and the Spike receptor-binding domain (RBD) binding data alone. Comparative glycoproteomics of the Spike RBD of wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) variants reveal O-glycosylation differences as a key determinant of immune recognition differences. These data underscore the interplay between viral glycosylation and immune recognition and reveal lectin fingerprinting to be a rapid, sensitive, and high-throughput assay to distinguish the neutralization potential of antibodies that target critical viral glycoproteins. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3XJOOF2LT | ||||||||||||
| Subjects: | 0 | ||||||||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2995: Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel | ||||||||||
| Status: | New | |||||||||
| Description: | Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2–specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3P9YIYFSH | |||||||||
| Subjects: | 0 | |||||||||
| Study PI, contact: |
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| Clinical Assessments: | None | |||||||||
| SDY2996: Robust neutralizing antibodies to SARS-CoV-2 infection persist for months | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection. | ||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3OCOE2N5M | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
| Study PI, contact: |
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| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2998: CD4 T cell response to FluBlok adjuvanted with R-DOTAP | |||||||
| Status: | New | ||||||
| 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: | 115 | ||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2999: High dose and standard dose fluzone vaccine titers | ||||||||||
| Status: | New | |||||||||
| Description: | Participants were vaccinated with either a high dose (HD) or standard dose (SD) of the fluzone influenza vaccine. Sera samples were collected and HAI assays were conducted to determine antibody titer. Mathematical model was used to map HAI titers to protection probabilities, and computed differences in vaccine efficacy of the HD compared to SD vaccine. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M35RNPGHO1 | |||||||||
| Subjects: | 0 | |||||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY3000: Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients. Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3KFTWUXGO | ||||||||||||
| Subjects: | 0 | ||||||||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||||||||
| SDY3001: BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | This study reports that most patients with NSCLC had a significant increase in the nAb response to the currently circulating Omicron variants after bivalent booster vaccination and had Ab titers comparable to healthy participants. Interestingly, though the durability of the nAb response persisted in most of the healthy participants, patients with NSCLC had significantly reduced nAb titers after 4-6 months of vaccination. Our data highlight the importance of COVID-19 bivalent booster vaccination as the standard of care for patients with NSCLC given the evolution of new variants of concern. | ||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M318VAYLD4 | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
| Study PI, contact: |
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| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY3002: Understanding heterogeneity of human bone marrow plasma cell maturation and survival pathways by single-cell analyses | ||||||||||
| Status: | New | |||||||||
| Description: | Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASCs) to long-lived plasma cells (LLPCs). We provide single-cell transcriptional resolution of 17,347 BM ASCs from five healthy adults. Fifteen clusters are identified ranging from newly minted ASCs (cluster 1) expressing MKI67 and high major histocompatibility complex (MHC) class II that progress to late clusters 5-8 through intermediate clusters 2-4. Additional ASC clusters include the following: immunoglobulin (Ig) M predominant (likely of extra-follicular origin), interferon responsive, and high mitochondrial activity. Late ASCs are distinguished by G2M checkpoints, mammalian target of rapamycin (mTOR) signaling, distinct metabolic pathways, CD38 expression, utilization of tumor necrosis factor (TNF)-receptor superfamily members, and two distinct maturation pathways involving TNF signaling through nuclear factor κB (NF-κB). This study provides a single-cell atlas and molecular roadmap of LLPC maturation trajectories essential in the BM microniche. Altogether, understanding BM ASC heterogeneity in health and disease enables development of new strategies to enhance protective ASCs and to deplete pathogenic ones. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3XNFR0AXP | |||||||||
| Subjects: | 0 | |||||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: |
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| Clinical Assessments: | None | |||||||||
| SDY3003: Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer | ||||||||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||||||||
| Description: | In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients-median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers. | |||||||||||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3H6V7QZH4 | |||||||||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||||||||
| Study PI, contact: |
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| Assays: |
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| Clinical Assessments: | None | |||||||||||||||||||||||||||
| SDY3005: Vaccine efficacy of seasonal COBRA in mice | ||||||||||
| Status: | New | |||||||||
| Description: | Not Provided | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3WW0CX28Y | |||||||||
| Subjects: | 261 | |||||||||
| Study PI, contact: |
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| Publications: |
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| Resources: |
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| Assays: | None | |||||||||
| Clinical Assessments: |
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| SDY3008: Single CyTOF analysis of samples from longitudinal studies of vaccine response to flu vaccines | |||||||||||||
| Status: | New | ||||||||||||
| Description: | This study contains CyTOF data from a subset of samples that were also analyzed by CyTOF in other ImmPort studies: SDY887, SDY314, SDY312, SDY311, SDY112, SDY315, SDY478, SDY1464. Since these samples were from participants who donated blood in multiple successive years, analyzing them on a year-by-year basis was not ideal, due to confounding of batch effects and biological aging effects. As such, we chose the participants with the largest number of repeat samples across years, and performed a single CyTOF analysis of those samples here. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3QQV0LLH0 | ||||||||||||
| Subjects: | 30 | ||||||||||||
| Study PI, contact: |
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| Publications: | None | ||||||||||||
| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||||||||
Updated Studies
| SDY56: Systems Biology of 2010 trivalent Influenza vaccine (TIV) in young and elderly (see companion study SDY61 2007, SDY270 2009, SDY119 2011) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Study Objective To identify innate signatures that correlate with the magnitude, quality and persistence of B cell responses after vaccination with TIV in the young versus the elderly. Study Design Single center, open label study in which adult healthy volunteers with no contraindications to immunization will be vaccinated with TIV. Blood samples will be collected on Days D0 (at enrollment) and D1, D3, D7, D14, D30, D180 post vaccination to study innate and/or adaptive immunity markers. Even though influenza vaccination is considered safe, volunteers will be asked to report any local or systemic AEs from Day 0 (vaccination) to Day 7 in memory aids. Reactogenicity events will also be evaluated by injection site examination on visits at D0, D1, D3 and D7. Volunteers will be also asked to report local and systemic AEs developing the day of a blood draw. Additionally, only AEs considered related (unlikely, possibly, probably or definitely related) will be collected and reported in this study from Day 0 (vaccination) to Day 180. After Day 30 only related SAEs will be collected and reported. Study Duration 12 months (6 months accrual and 6 months follow-up period) |
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| Program/Contract: |
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| DOI: | 10.21430/M3X9SKF8RQ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 70 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Study PI, contact: |
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| Clinical Assessments: |
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| SDY59: Generation of Memory T cells In Young Healthy and Immunocompromised Populations | |||||||
| Status: | Updated | ||||||
| Description: | To expand our study of T cell memory repertoires to include healthy children who should still be in the process of generating memory repertoires. These studies will provide data about the age dynamics of memory repertoires. In addition to children, we will examine flu-specific memory repertoires in children with autoimmune diseases who are undergoing mild immunosuppression. This should describe the effects of immunosuppressive therapy on memory formation and function. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3PUJHYDDZ | ||||||
| Subjects: | 223 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY421: Clonal B cell response to naturally occurring pathogens causing tissue specific immune responses in human | |||||||
| Status: | Updated | ||||||
| Description: | Elucidate the trafficking specificity, or diversity, of clonal B cell responses to mucosae-associated illnesses or infections in vivo. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3S1P8RAII | ||||||
| Subjects: | 4 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY460: B and T Cell Determinants of Influenza Vaccine Responses in the Elderly 2008 (see companion study SDY773) | |||||||
| Status: | Updated | ||||||
| Description: | Application of high-throughput DNA sequencing of the IGH gene rearrangements to study the B cell repertoires over two successive years in 27 individuals ranging in age from 20 to 89 years old. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M34OUDCFO2 | ||||||
| Subjects: | 27 | ||||||
| Study PI, contact: |
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY508: Humoral responses to West Nile virus | |||||||
| Status: | Updated | ||||||
| Description: | Integrate two high-throughput technologies namely, microengraving-based screening of primary B cells and next-generation sequencing to examine the relationship between the diversity and quality of humoral responses raised and the severity of disease. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3WVUCYBW9 | ||||||
| Subjects: | 12 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
| Resources: |
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY652: Mouse recombination path counting on a gpu | |||||||
| Status: | Updated | ||||||
| Description: | The goal of the experiment is to test whether convergent recombination predicts TCRb in vivo frequency, by combining high throughput TCRb sequencing on the Roche 454 platform and highthrougput comprehensive TCRb in silico recombination path counting on a graphical processing unit. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3LVYI9ULI | ||||||
| Subjects: | 2 | ||||||
| Study PI, contact: |
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| Clinical Assessments: | None | ||||||
| SDY675: Heritable influence on the B and T cell receptor repertoire | |||||||
| Status: | Updated | ||||||
| Description: | The adaptive immune systems capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is frequently underestimated. By leveraging the unique characteristics of B, CD4+ T, and CD8+ T lymphocyte subsets isolated from monozygotic twins, we have elucidated the impact of heritable factors on the V(D)J recombination process and have shown that the repertoires of both naive and antigen experienced cells are subject to biases resulting from initial recombination differences. Moreover, we show that the relative usage of V and J gene segments is chromosomally biased, with approximately 1.5 times as many rearrangements originating from a single chromosome. These data refine our understanding of the heritable mechanisms affecting the repertoire, and show that bias exists on a chromosome-wide level. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3XMYVQI9X | ||||||
| Subjects: | 10 | ||||||
| Study PI, contact: |
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY773: B and T Cell Determinants of Influenza Vaccine Responses in the Elderly SLVP015 2009 (see companion study SDY460) | |||||||
| Status: | Updated | ||||||
| Description: | Application of high-throughput DNA sequencing of the IGH gene rearrangements to study the B cell repertoires over two successive years in 27 individuals ranging in age from 20 to 89 years old. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M35OPGLUTH | ||||||
| Subjects: | 27 | ||||||
| Study PI, contact: |
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| Assays: |
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| Clinical Assessments: | None | ||||||
| SDY984: Zoster vaccine in young and elderly | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Study objective: To analyze the generic innate immune signatures that correlate with the magnitude of the adaptive immune responses (by gamma-interferon ELISPOT, responder-cell frequency (RCF) and flow cytometric studies) in young and elderly populations in order to identify the correlation signatures of the innate immune responses to Zoster vaccine.Study design: Double center, open label study in which adult healthy volunteers will be vaccinated with Zoster vaccine. Blood samples will be collected during a screening visit (between days D-56 to D-14) D0 (at vaccination) and D1, D3, D7, D14, D30, D90 and D180 post vaccination to study innate and adaptive immunity responses. Even though Zoster vaccine is considered safe, volunteers are asked to report and record any local or systemic AEs for 7 days post-vaccination. Also AEs will be reported for 30 days post-vaccination any SAE for 180 days post vaccination. AEs developing the day of the blood draw will also be reported | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M36N1BYFT5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 77 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY1043: A Haystack Heuristic for Autoimmune Disease Biomarker Discovery Using Next-Gen Immune Repertoire Sequencing Data | ||||||||||
| Status: | Updated | |||||||||
| Description: | In this work, we present a new algorithm that employs local search techniques to discover statistically significant patient-specific motifs in large-scale immune-repertoire datasets. We apply our methodology successfully to our multi-million-sequence immune repertoire dataset to discover a statistically significant MS-specific motif. The discovered sequence motif could potentially serve as biomarker for the clinical diagnosis of Multiple Sclerosis. The presented methodology is efficient and generalizable to other high throughput sequencing datasets. | |||||||||
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| DOI: | 10.21430/M3HUHJSPBP | |||||||||
| Subjects: | 97 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY1361: B cell sequencing data from individuals with kidney transplantation (SNS01) | ||||||||||
| Status: | Updated | |||||||||
| Description: | This data comes from peripheral blood from individuals that had a kidney transplantation. The study is a longitudinal study with data collected at time 0 (considered pre-transplant), 6 and 24 months after the transplant. They are classified in three clinical outcomes defined by pathology reads of serial allograft biopsies scored by Banff criteria and the chronic allograft damage index (CADI) score: Non progressors (NP; n=10) had low non incremental CADI score without acute rejection, progressors with no rejection (PNR; n=10) had incremental CADI score over 2 years without rejection, and progressors with rejection (PR; n=7) had incremental high CADI scores over 2 years with rejection episodes. This data reveal that the immune repertoire diversity of individuals that reject the organ is higher in comparison with those that did not reject the organ. Additionally, after 2 years of follow-up, patients who developed rejection show an overall reduction of B-celll diversity with persistence in and expansion of specific clones. | |||||||||
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| DOI: | 10.21430/M37EGAHB65 | |||||||||
| Subjects: | 27 | |||||||||
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| SDY1389: Lymph node reservoirs for long-lived memory T cells | |||||||||
| Status: | Updated | ||||||||
| Description: | Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. Here, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors, and identify a subset of memory CD8+T cells in LN which maintain a distinct differentiation and functional profile compared to memory CD8+T cells in blood, spleen, bone marrow (BM), and lungs. Whole transcriptome and high dimensional CyTOF profiling reveals that LN memory CD8+T cells express signatures of quiescence and self-renewal compared to corresponding populations in blood, spleen, BM and lung. LN memory T cells exhibit a distinct transcriptional signature including expression of stem cell-associated transcription factors TCF-1, LEF-1, T-follicular helper cell markers CXCR5, and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8+T cells identified in chronic infection models which responds to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to T cell receptor (TCR)-mediated stimulation and maintain higher TCR clonal diversity compared to memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies. | ||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3NBGEA98C | ||||||||
| Subjects: | 51 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY1613: Paired Heavy and Light Chain Immunoglobulin Reconstruction in Single-Cell RNA-Seq Data | |||||||
| Status: | Updated | ||||||
| Description: | We generated scRNA-Seq data for 20 human plasmablasts induced by seasonal flu vaccination.To reconstruct the paired heavy and light chain antibody genes, we developed several different in silico filtering strategies to enrich immunoglobulin transcripts, and then applied de novo assembly. This method successfully reconstructed productive IgH and IgL chains in 100% of cells analyzed. The accuracy of clonotype-assignment of individual cells was 94.5-98%, as validated by comparing BCR sequences reconstructed from NGS to those obtained by conventional single-B cell cloning methodology. This makes it possible to link the transcriptional programming of individual B cell clones at critical developmental stages with the eventual fate of the clonal lineage in vivo. | ||||||
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| DOI: | 10.21430/M351ZMQT4J | ||||||
| Subjects: | 3 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1769: Maternal and Infant Immune Repertoire Sequencing in PPROM study | ||||||||||
| Status: | Updated | |||||||||
| Description: | To identify distinct features of immunoglobulin and T-cell receptor development in Preterm labor, the study analyzed T-cell receptor beta chain (TCR-β) and immunoglobulin heavy chain (IgH) diversity, CDR3 lengths, clonal sharing, and preferential usage of variable (V), diversity (D), and joining (J) gene segments. Additionally, the rates of somatic hypermutation (SHM) in IgH were studied. Overall, the cord blood IgH repertoires had significantly (padj < 0.05) lower rates of SHM and both TCR-β and IgH repertoires had shorter CDR3s compared to maternal blood. From the comparative analysis of term vs PPROM cord blood samples, RESULTs 1) CDR3 lengths correlated with gestational age, with the shorter CDR3s in preterm neonates suggesting a ‘less developed’ repertoire. 2) Preterm cord blood displayed preferential usage of a number of V genes and J genes. 3) the term maternal repertoires displayed significant preferential usage of TRBV7-8 compared to preterm maternal repertoires. 4) Significantly higher prevalence of convergent clones between mother/baby pairs in preterm pregnancies. Together, these results suggest the repertoire of preterm infants displays a combination of immature features yet preferential use of particular genes and convergence with maternal TCR-β clones. While the higher TCR-β diversity might reflect less clonal expansion, the higher clonal convergence between mothers and infants in PTL could represent mother and fetus both responding to a shared stimulus like an infection. These data provide a detailed analysis of the maternal-fetal immune repertoire in term and preterm patients, and contribute to a better understanding of neonate immune repertoire development and potential changes associated with preterm labor | |||||||||
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| DOI: | 10.21430/M3GUQMUDWL | |||||||||
| Subjects: | 48 | |||||||||
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| SDY1885: Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex | |||||||||||
| Status: | Updated | ||||||||||
| Description: | The persistence of anti-viral immunity throughout the human body is essential for protection, and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We used flow cytometry, T cell receptor analysis, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8+ T cells recognizing ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines overall magnitude, tissue distribution, differentiation, and clonal repertoire of virus-specific T cells. Age and sex influence T cell differentiation and dissemination in tissues, while T cell tissue residence and functionality is highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, important for targeting, monitoring, and predicting immune responses to existing and emerging viruses. | ||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3Z6V3I3QM | ||||||||||
| Subjects: | 59 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1964: Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine | ||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||
| Description: | The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12??g lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n?=?6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates. | |||||||||||||||||||||
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| DOI: | 10.21430/M3YD38IFGB | |||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||
| SDY1976: Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigenspecific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens. | ||||||||||||
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| DOI: | 10.21430/M3TGZSFQZZ | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2033: Vaccine protection against the SARS-CoV-2 Omicron variant in macaques | |||||||||||||||
| Status: | Updated | ||||||||||||||
| Description: | The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers and undetectable Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Moreover, virologic control correlated with both antibody and T cell responses. These data suggest that both humoral and cellular immune responses contribute to vaccine protection against a highly mutated SARS-CoV-2 variant. | ||||||||||||||
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| DOI: | 10.21430/M36QZ9VXR6 | ||||||||||||||
| Subjects: | 0 | ||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||
| SDY2041: Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | The Ad26.COV2.S vaccine1-3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I-IIa clinical trial2 against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern. | ||||||||||||||||||
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| DOI: | 10.21430/M3RLFPEUYM | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2043: One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1-receptor binding domain (RBD) and S1-N-terminal domain. For diagnosis, the combined [IgA + IgG + IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values ?0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients-a possible source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19-vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2-specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines. | ||||||||||||
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| DOI: | 10.21430/M3FRD03J1F | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2111: Reduced COVID-19 Vaccine Response in Patients Treated with Biologic Therapies for Asthma | ||||||||||
| Status: | Updated | |||||||||
| Description: | It is unclear if patients with severe asthma and atopic dermatit is on biologic therapies have an adequate and durable humoral immune response after vaccination to SARS-CoV-2. To address these questions, we conducted a prospective observational trial from February 2021 to September 2021 with adults who had severe asthma or atopic dermatitis treated with benralizumab (IL-5 receptor antagonist), mepolizumab(IL-5 antagonist), or dupilumab (IL-4 receptor a antagonist). | |||||||||
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| DOI: | 10.21430/M3A944EBOX | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2119: Higher Proinflammatory Cytokines Are Associated With Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Background: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. Methods: A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons. Results: In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates < 0.05). Conclusions: A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs. | |||||||||||||||
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| DOI: | 10.21430/M3ERSVMISI | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2126: SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Understanding vaccine-mediated protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to overcoming the global coronavirus disease 2019 (COVID-19) pandemic. We investigate mRNA-vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three time points: before vaccination, after the first dose, and after the second dose. Following complete vaccination, both naive and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naive individuals were lower than in previously infected individuals. After the first vaccine dose, one-third of previously infected individuals lacked neutralizing antibodies; this was improved to one-fifth after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals. | ||||||||||||
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| DOI: | 10.21430/M3NGLEV4KG | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2172: Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | We wanted to determine whether MM patients without detectable anti-S IgG antibodies to SARS-CoV-2 immunization (seronegative) had detectable SARSCoV-2 B and T cell responses after SARS-CoV-2 vaccination, which would possibly provide some protection against severe disease even in the absence of anti-S antibodies. In order to assay quantitative and qualitative differences in T cell responses, we adopted a high-resolution flow cytometry assay that incorporates multiple cytokines and activation markers. Such data are urgently required to guide masking, social distancing, and passive antibody/booster vaccination strategies for potentially vulnerable MM patients treated with these anti-cancer agents as we enter the second fall season of the COVID-19 pandemic. | |||||||||||||||
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| DOI: | 10.21430/M3JLICY0TG | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2221: Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination | |||||||||
| Status: | Updated | ||||||||
| Description: | SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19 vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2) and Omicron BA.1.1 in the BAL compared to COVID-19 convalescents, despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses, not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during re-infection, but offer limited protection against breakthrough infection, especially by Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by Omicron sublineage and future VOCs. | ||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3N3Q6QZUY | ||||||||
| Subjects: | 0 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY2248: Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | PURPOSE Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron). MATERIALS AND METHODS Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined. RESULTS Mean anti-SARS-CoV-2 spike immunoglobulin G–binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers (P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/μL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron. CONCLUSION Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response. | |||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3DBDOJHGH | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2256: SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques | |||||||||||||||||
| Status: | Updated | ||||||||||||||||
| Description: | The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19. | ||||||||||||||||
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| DOI: | 10.21430/M30RR7BFU2 | ||||||||||||||||
| Subjects: | 0 | ||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||
| SDY2260: A bivalent SARS-CoV-2 monoclonal antibody combination does not impact the immunogenicity of a vector-based COVID-19 vaccine in macaques | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Human monoclonal antibodies (mAbs) that target the spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) offer a promising approach for the prevention and treatment of coronavirus disease 2019 (COVID-19). Given suboptimal global vaccination rates, waning immunity in vaccinated individuals, and the emergence of SARS-CoV-2 variants of concern, the use of mAbs for COVID-19 prevention may increase and may need to be administered together with vaccines in certain settings. However, it is unknown whether administration of mAbs will impact the immunogenicity of SARS-CoV-2 vaccines. Using an adenovirus vector-based SARS-CoV-2 vaccine, we show that simultaneous administration of the vaccine with SARS-CoV-2 mAbs does not diminish vaccine-induced humoral or cellular immunity in cynomolgus macaques. These results suggest that SARS-CoV-2 mAbs and viral vector-based SARS-CoV-2 vaccines can be administered together without loss of potency of either product. Additional studies will be required to evaluate co-administration of mAbs with other vaccine platforms. | ||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3YQRTHK52 | ||||||||||
| Subjects: | 0 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY2385: Significant Reduction in Vaccine Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination | |||||||
| Status: | Updated | ||||||
| Description: | Antibody decline occurred from 2 weeks to 6 months post-BNT162b2 mRNA vaccination in nursing home (NH) residents and healthcare workers. Antispike, receptor-binding domain, and neutralization levels dropped >81% irrespective of prior infection. Notably, 69% of infection-naive NH residents had neutralizing antibodies at or below the assay’s limit of detection. | ||||||
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| DOI: | 10.21430/M3ET0ZGOYY | ||||||
| Subjects: | 0 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2406: Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2. | ||||||||||||
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| DOI: | 10.21430/M3T7A0KV72 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2421: Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody response against the spike protein of five major SARS-CoV-2 variants, D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in health care workers (HCWs) vaccinated with SARS-CoV-2 mRNA vaccines. Serum samples were collected before vaccination, 3 weeks after first vaccination, 1 month after second vaccination, and 6 months after second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for most patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein-bearing pseudoviruses declined markedly from 1 to 6 months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. In addition, mRNA-1273-vaccinated HCWs exhibited about twofold higher neutralizing antibody titers than BNT162b2-vaccinated HCWs. Together, these results demonstrate possible waning of antibody-mediated protection against SARS-CoV-2 variants that is dependent on prior infection status and the mRNA vaccine received. They also show that the Omicron variant spike protein can almost completely escape from neutralizing antibodies elicited in recipients of only two mRNA vaccine doses. | ||||||||||||||||||
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| DOI: | 10.21430/M3OD3ZIDCF | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2436: Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections | |||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||
| Description: | Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)-specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells. | ||||||||||||||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3VPZ743F1 | ||||||||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||||||||
| SDY2522: Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC. | ||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3CZV2762J | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2546: COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Methods: We longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained. Findings: Booster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents' and 28% HCWs' titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/m3r5h37fu9 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2549: Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2 | |||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||
| Description: | B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV. | ||||||||||||||||||||||||
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| DOI: | 10.21430/m3rtb0hobg | ||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||
| SDY2574: Dissecting Functional Antibody Activity Against Influenza Virus | ||||||||||
| Status: | Updated | |||||||||
| Description: | Not Provided | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/m3butykv0a | |||||||||
| Subjects: | 51 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2580: Polymer delivery of Influenza Vaccine | |||||||
| Status: | Updated | ||||||
| Description: | Not Provided | ||||||
| Program/Contract: |
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| DOI: | 10.21430/m3c49tyd79 | ||||||
| Subjects: | 61 | ||||||
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| SDY2581: Host Predictors of Broadly Cross-Reactive Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern Differ Between Infection and Vaccination | ||||||||||
| Status: | Updated | |||||||||
| Description: | Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policymakers on the populations most likely to require vaccine booster in an institutional review board approved prospective observational cohort study of staff at St. Jude Childrens Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated immunoglobulin G (IgG) levels by enzyme-linked immunosorbent assay to the spike receptor binding domain (RBD) from 5 important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1, and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against 1 or multiple viral variants. Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those who did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations, including immunocompromised, elderly, and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses.Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on populations that may require follow-on immunization. | |||||||||
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| DOI: | 10.21430/m3f139urpw | |||||||||
| Subjects: | 237 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2591: COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood | ||||||||||
| Status: | Updated | |||||||||
| Description: | Introduction: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and cross-neutralization capacity of maternal and cord antibody responses to SARS-CoV-2 variants following COVID-19 vaccination in pregnancy can inform neonatal immunity. Methods: Here we characterized the binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants. In addition, we evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. Results: Our results reveal that the current COVID-19 vaccination induced significantly higher RBD-specific binding IgG titers in cord blood compared to maternal blood for both the Wuhan and Omicron BA1 strain. Interestingly, the binding IgG antibody levels for the Omicron BA1 strain were significantly lower when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, and BA4/5 specific neutralizing antibody levels were significantly lower compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not detected in either maternal or cord blood. Discussion: Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for the Wuhan and Delta variants but not for the Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for bivalent boosters as new variants emerge. | |||||||||
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| DOI: | 10.21430/M3Q9XHM545 | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2607: Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases | ||||||||||
| Status: | Updated | |||||||||
| Description: | Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2- or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti-SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs. | |||||||||
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| DOI: | 10.21430/M32BIF6Z4Z | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2631: Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential. | ||||||||||||
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| DOI: | 10.21430/M3KG3AGBNR | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2633: Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals. | |||||||||||||||
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| DOI: | 10.21430/M3MRUIWTXB | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| SDY2658: Dysregulated naive B cells and de novo autoreactivity in severe COVID-19 | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2–5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6–10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19. Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10–15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae. | ||||||||||||||||||
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| DOI: | 10.21430/M3BG5XDB1N | ||||||||||||||||||
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| SDY2659: NK T cells SARS-CoV-2 | |||||||
| Status: | Updated | ||||||
| Description: | Immune responses in pregnant women | ||||||
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| DOI: | 10.21430/M3TFVC6NAQ | ||||||
| Subjects: | 128 | ||||||
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| SDY2673: Next Generation Methodology for Updating Computationally Optimized Broadly Reactive Antigen (COBRA) HA Vaccines Against Emerging Human Seasonal Influenza A(H3N2) Viruses | ||||||||||
| Status: | Updated | |||||||||
| Description: | Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates. | |||||||||
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| DOI: | 10.21430/M388O87C8Y | |||||||||
| Subjects: | 135 | |||||||||
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| SDY2675: Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Background Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies. Methods In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation’s largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders). Results Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes. Conclusions In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3Y9V69ZJQ | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Assays: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SDY2691: Testing vaccine efficacy using electrospray | |||||||
| Status: | Updated | ||||||
| Description: | Production of cGAMP MPs using electrospray apparatuses, characterization of the resulting MPs, and comparison of their activity as vaccine adjuvants in vitro and in vivo | ||||||
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| DOI: | 10.21430/M3M2WEHXF8 | ||||||
| Subjects: | 51 | ||||||
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| SDY2728: Longitudinal Assessment of BNT162b2- and mRNA-1273-Induced Anti-SARS-CoV-2 Spike IgG Levels and Avidity Following Three Doses of Vaccination | ||||||||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||||||||
| Description: | SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were assessed for circulating anti-SARS-CoV-2 spike IgG levels and avidity for up to 6 months post-primary series and 9 months after the third dose. Following primary series vaccination, anti-SARS-CoV-2 spike IgG levels declined from months 1 to 6, while avidity increased through month 6, irrespective of the vaccine received. The third dose of either vaccine increased anti-SARS-CoV-2 spike IgG levels and avidity and appeared to enhance antibody level persistence— generating a slower rate of decline in the 3 months following the third dose compared to the decline seen after the primary series alone. The third dose of both vaccines induced significant avidity increases 1 month after vaccination compared to the avidity response 6 months post-primary series vaccination (p ≤ 0.001). A significant difference in avidity responses between the two vaccines was observed 6 months post-third dose, where the BNT162b2 recipients had higher antibody avidity levels compared to the mRNA-1273 recipients (p = 0.020). | |||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M36Q446TZ2 | |||||||||||||||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||||||||||||||
| SDY2777: Targeted electronic health record-based recruitment strategy to enhance COVID-19 vaccine response clinical research study enrollment | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Efficient recruitment of eligible participants is a significant challenge for clinical research studies. This challenge was exacerbated during the COVID-19 pandemic when in-person recruitment was not an option. In 2020, the University of Minnesota was tasked, as part of the National Cancer Institute's Serological Sciences Network for COVID-19 (SeroNet), to recruit participants for a longitudinal serosurveillance clinical research study with a goal of characterizing the COVID-19 vaccine-elicited immune response among immunocompromised individuals, which necessitated reliance on non-traditional strategies for participant recruitment. To meet our enrollment target of 300 transplant patients, 300 cancer patients, 100 persons living with HIV, and 200 immunocompetent individuals, we utilized targeted electronic health record (EHR)-based recruitment in addition to traditional recruitment tools, which was an effective combination of recruitment strategies. A significant advantage of patient portal messaging or other digital recruitment strategies such as email communication is timing. We reached 85 % (769 out of 900) of our enrollment target within one year with a 14.3 % response rate to invitations to participate in our study. This achievement is perhaps more salient given the COVID-19 pandemic-related constraints within which we were operating. We demonstrated that the EHR can be leveraged to quickly identify potentially eligible study participants either via EHR communication or mail. We also illustrate how the online portal MyChart can be used to efficiently send targeted recruitment messages. | ||||||||||||
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| DOI: | 10.21430/M3OFED88WB | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
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| SDY2792: Immunogenicity of BA.5 Bivalent mRNA Vaccine Boosters | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Waning immunity after messenger RNA (mRNA) vaccination and the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to reduced mRNA vaccine efficacy against symptomatic infection and severe disease. Bivalent mRNA boosters (manufactured by Pfizer–BioNTech and Moderna) expressing the spike protein of the B.1.1.529 (omicron) BA.5 sublineage and the ancestral WA1/2020 strain have been developed because BA.5 substantially evades neutralizing antibodies. However, the immunogenicity of the BA.5-containing bivalent mRNA boosters remains unknown. | ||||||||||||
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| DOI: | 10.21430/M3GSREONEE | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2802: Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers | ||||||||||
| Status: | Updated | |||||||||
| Description: | Background Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents. Methods: Nursing home residents (N = 143) and HCWs (N = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.1) strain spike proteins, and by bead-multiplex immunoglobulin G immunoassay to Wuhan spike protein and its receptor-binding domain (RBD). Cytomegalovirus serology and levels of inflammatory biomarkers were also measured. Results: Severe acute respiratory syndrome coronavirus 2-naive CMV seropositive (CMV+) HCWs had significantly reduced Wuhan-neutralizing Ab (P = .013), anti-spike (P = .017), and anti-RBD (P = .011) responses 2 weeks after primary vaccination series compared with responses among CMV seronegative (CMV−) HCWs, adjusting for age, sex, and race. Among NH residents without prior SARS-CoV-2 infection, Wuhan-neutralizing Ab titers were similar 2 weeks after primary series but were reduced 6 months later (P = .012) between CMV+ and CMV− subjects. Wuhan-neutralizing Ab titers from CMV+ NH residents who had prior SARS-CoV-2 infection consistently trended lower than titers from SARS-CoV-2 experienced CMV− donors. These impaired Ab responses in CMV+ versus CMV− individuals were not observed after booster vaccination or with prior SARS-CoV-2 infection. Conclusions: Latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein, a neoantigen not previously encountered, in both HCWs and NH residents. Multiple antigenic challenges may be required for optimal mRNA vaccine immunogenicity in CMV+ adults. | |||||||||
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| DOI: | 10.21430/M3LNVQE4HE | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2809: Nasally delivered interferon lambda protects mice against SARS-CoV-2 infection | |||||||
| Status: | Updated | ||||||
| Description: | Here, we show that IFN-l protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice | ||||||
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| DOI: | 10.21430/M3FGEA29GM | ||||||
| Subjects: | 253 | ||||||
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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: | Updated | ||||||
| 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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| SDY2968: COVID-19 vaccination perspectives among patients with Long COVID: A qualitative study | ||||||||||
| Status: | Updated | |||||||||
| Description: | Individuals who have Long COVID may have unique perspectives about COVID-19 vaccination due to the significant impact that COVID-19 has had on their lives. However, little is known about the specific vaccination perspectives among this patient population. The goal of our study was to improve our understanding of perspectives about COVID-19 vaccines among individuals with Long COVID. Interviews were conducted with patients receiving care at a post-COVID recovery clinic. Deductive thematic analysis was used to characterize participant perspectives according to the vaccine acceptance continuum framework, which recognizes a spectrum from vaccine acceptance to refusal. From interviews with 21 patients, we identified perspectives across the continuum of vaccine acceptance. These perspectives included acceptance of vaccines to prevent future illness, concerns about vaccine side effects on Long COVID symptoms, and refusal of vaccines due to perceived natural immunity. A limitation of our study is that these perspectives are specific to individuals receiving care at one post-COVID recovery clinic. In conclusion, our study demonstrates that some patients with Long COVID are uncertain about COVID-19 vaccines and boosters but may also be amenable to conversations that impact future vaccination acceptance. Patient perspectives should be considered when communicating recommendations for COVID-19 vaccinations to this population. | |||||||||
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| DOI: | 10.21430/M3J8UMVGT6 | |||||||||
| Subjects: | 0 | |||||||||
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