DR50.1 DataRelease
Release Date: January 2024
New Studies: 27
Updated Studies: 2
New Studies
| SDY1465: Monozygotic and Dizygotic Twin Pair T-Cell Responses to Influenza Vaccination SLVP018 2012 | |||||||||
| Status: | New | ||||||||
| Description: | Evaluate the variation in immune response between individuals and assess whether it changes as a function of age and similarity in genetic and environmental background (by comparing differences between monozygotic and dizygotic twin pairs of different ages). | ||||||||
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| DOI: | 10.21430/M3EPDNX0XF | ||||||||
| Subjects: | 23 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY1472: Immune Senescence: Comparison of Immune Response to Influenza Vaccine 2007 in Adults of Different Ages | |||||||||||
| Status: | New | ||||||||||
| Description: | Systems biology approach to examine effects of seasonal flu vaccination in adults of different ages on gene expression, cytokine stimulation and serum cytokines with parameters such as immune senescence to uncover new markers and mechanisms behind failure of immune function in many older people. | ||||||||||
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| DOI: | 10.21430/M3XRXDHVW9 | ||||||||||
| Subjects: | 19 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1479: Plasmablast response to inactivated and live attenuated influenza vaccines (TIV3/TIV3 ID) in 2014 | |||||||||||
| Status: | New | ||||||||||
| Description: | The aim of this study is to compare the response to different formulations of licensed influenza vaccines. The type of seasonal influenza vaccination(s) received independently by volunteers in the year(s) since their last study visit will not impact eligibility. Volunteers will be assigned into one of three vaccine groups (intramuscular trivalent inactivated influenza vaccine (TIV); live attenuated influenza vaccine (LAIV- given year 1 only) or intradermal TIV, based on the type of study vaccine they received in 2010, 2011, 2012, or 2013. All participants will receive a single dose of their assigned seasonal influenza vaccine. Volunteers will complete 3 study visits at Day 0, Day 6-8 and Day 24-32. | ||||||||||
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| DOI: | 10.21430/M3PHCIW62R | ||||||||||
| Subjects: | 19 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1480: Genetic and Environmental Factors in the Response to Influenza Vaccination 2014 | |||||||||||
| Status: | New | ||||||||||
| Description: | This is a phase IV study of 120 healthy 12-49 year old adolescents and adult volunteers who are given licensed seasonal influenza vaccine. There are no exclusions for gender, ethnicity or race. The volunteers will be enrolled into one of 3 groups: Group A: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+ 7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group B: Up to 40 healthy dizygotic (DZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group C: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be randomized within the twin pair to receive either inactivated influenza vaccine quadrivalent (IIV4) or live, attenuated influenza vaccine quadrivalent (LAIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). This group was discontinued in 2016 due to ACIP recommendations against the use of LAIV but may be reopened in 2018 pending LAIV4 availability. Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs. | ||||||||||
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| DOI: | 10.21430/M3E3KCYPU4 | ||||||||||
| Subjects: | 54 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1481: Genetic and Environmental Factors in the Response to Influenza Vaccination 2014 | |||||||||
| Status: | New | ||||||||
| Description: | This is a phase IV study of 120 healthy 12-49 year old adolescents and adult volunteers who are given licensed seasonal influenza vaccine. There are no exclusions for gender, ethnicity or race. The volunteers will be enrolled into one of 3 groups: Group A: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+ 7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group B: Up to 40 healthy dizygotic (DZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group C: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be randomized within the twin pair to receive either inactivated influenza vaccine quadrivalent (IIV4) or live, attenuated influenza vaccine quadrivalent (LAIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). This group was discontinued in 2016 due to ACIP recommendations against the use of LAIV but may be reopened in 2018 pending LAIV4 availability. Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs. | ||||||||
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| DOI: | 10.21430/M3KVQXST4E | ||||||||
| Subjects: | 54 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY1482: Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029) | |||||||||||
| Status: | New | ||||||||||
| Description: | This is a study of healthy children and adults receive the current seasonal influenza vaccine. The volunteers were enrolled into one of 7 groups over a 5-year period. Immunization is administered; blood samples and NP swabs are collected at various time points based on groups assigned. Group A (LAIV4/annual return), Group B (LAIV4/ single year), Group C (LAIV4/NP swab group), Group D (IIV4/annual return), Group E (IIV4/single year), Group F (LAIV4/single year), Group G (IIV4/single year) | ||||||||||
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| DOI: | 10.21430/M3O4HKKCJR | ||||||||||
| Subjects: | 53 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1483: Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029) | |||||||||
| Status: | New | ||||||||
| Description: | This is a study of healthy children and adults receive the current seasonal influenza vaccine. The volunteers were enrolled into one of 7 groups over a 5-year period. Immunization is administered; blood samples and NP swabs are collected at various time points based on groups assigned. Group A (LAIV4/annual return), Group B (LAIV4/ single year), Group C (LAIV4/NP swab group), Group D (IIV4/annual return), Group E (IIV4/single year), Group F (LAIV4/single year), Group G (IIV4/single year) | ||||||||
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| DOI: | 10.21430/M34YFGITWS | ||||||||
| Subjects: | 53 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY1484: Role of CD4+ Memory Phenotype, Memory, and Effector T Cells in Vaccination and Infection (SLVP030) | |||||||||||
| Status: | New | ||||||||||
| Description: | This is a Phase IV study of up to 100 healthy children, ages 6 months to 10 years of age, who will receive either Flumist live, attenuated influenza virus vaccine, quadrivalent (LAIV4) or the current Fluzone inactivated influenza vaccine, quadrivalent (IIV4). The volunteers will be enrolled into one of 3 Groups (A, B, C). Volunteers will return each year until 2018-2019 for annual flu immunizations and study visits. Questionnaires will be administered annually to record demographic characteristics, vaccination history, exposure to animals, day care and medically attended illness. There are no exclusions for gender, ethnicity or race. Volunteers in Group C will also receive the measles, mumps, rubella and varicella (MMRV) vaccine at approximately 12-15 months of age (to be administered by the volunteers' personal pediatrician, not as a study vaccine). They will then come for a study visit to collect blood 60 days later. Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs. | ||||||||||
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| DOI: | 10.21430/M3VRIZVVE5 | ||||||||||
| Subjects: | 30 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY2187: Microbiome Preterm Birth DREAM Challenge | ||||||||||||||
| Status: | New | |||||||||||||
| Description: | Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi. We validated the crowdsourced models on novel datasets representing 331 samples from 148 pregnant individuals. From 318 DREAM challenge participants we received 148 and 121 submissions for our two separate prediction sub-challenges with top-ranking submissions achieving bootstrapped AUROC scores of 0.69 and 0.87, respectively. Alpha diversity, VALENCIA community state types, and composition (via phylotype relative abundance) were important features in the top performing models, most of which were tree based methods. This work serves as the foundation for subsequent efforts to translate predictive tests into clinical practice, and to better understand and prevent preterm birth. | |||||||||||||
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| DOI: | 10.21430/M3JMMPMLSP | |||||||||||||
| Subjects: | 764 | |||||||||||||
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| Assays: | None | |||||||||||||
| Clinical Assessments: | None | |||||||||||||
| SDY2189: Systems vaccinology of the BNT162b2 mRNA vaccine in humans | |||||||||||||||
| Status: | New | ||||||||||||||
| Description: | The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFN_; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization. | ||||||||||||||
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| DOI: | 10.21430/M3I1AFHGHU | ||||||||||||||
| Subjects: | 56 | ||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||
| SDY2393: Rhesus H-ARS Dose-Response Relationship | |||||||
| Status: | New | ||||||
| Description: | Rhesus macaques (Macaca mulatta) were exposed to total-body irradiation ranging from 500 cGy to 750 cGy at a dose rate of 50 cGy/min from a Co-60 source and were observed for 60 days for mortality and clinical signs. Each group consisted of 4 males and 4 females. Animals were provided with supportive care which included antibiotics, fluids, anti-ulcer, anti-emetics, analgesics, nutritional support, and wound disinfection administered according to pre-determined criteria, but were not provided blood transfusions. Blood was drawn at predetermined time points and blood cells were counted. Note: Day 1 is 24 hours after the day of irradiation, which is designated in the data files as Day -1. There is no Day 0. | ||||||
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| DOI: | 10.21430/M3ZAEP8Q6S | ||||||
| Subjects: | 48 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2472: Immunogenicity testing of a recombinant N1 vaccine candidate, N1-MPP, adjuvanted with CpG 1018 | ||||||||||
| Status: | New | |||||||||
| Description: | Naive, female 6-8 week old BALB/c mice were either vaccinated once with 3 ug of recombinant N1-MPP, 3 ug N1-MPP + 3ug CpG 1018, or 3 ug of an irrelevant protein, or twice with the same formulations after a three week interval. Three weeks post boost, mice were challenged with 10x LD50 of A/Singapore/GP1908/2015 (H1N1) virus, and weight loss and survival were monitored over 2 weeks. Afterward, serological analysis was conducted and transferred to naive mice who were then challenged with 5xmLD50 of 140 A/Singapore/GP1908/2015 H1N1 to assess immunity. To determine whether CpG 1018 improves NA immunogenicity, even in admixtures to QIV, another prime boost regiment was conducted, in QIV admixtures, and mice were challenged once more. | |||||||||
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| DOI: | 10.21430/M3H4WZ3N3A | |||||||||
| Subjects: | 327 | |||||||||
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| Publications: | None | |||||||||
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| SDY2473: SARS-CoV-2 mRNA vaccination elicits T follicular helper cell response | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individ- uals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine. | |||||||||||||||
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| DOI: | 10.21430/M3D2XKJ1VO | |||||||||||||||
| Subjects: | 15 | |||||||||||||||
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| Publications: | None | |||||||||||||||
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| Assays: | None | |||||||||||||||
| Clinical Assessments: | None | |||||||||||||||
| SDY2474: H1 priming provides lasting immunity against H5N1 | ||||||||||
| Status: | New | |||||||||
| Description: | Mouse infections, ADCC reporter assays and ELISAs were conducted to study the specific role of the HA on protection against infection without interference of cellular immunity or humoral anti-neuraminidase immunity were conducted | |||||||||
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| DOI: | 10.21430/M322ERFA05 | |||||||||
| Subjects: | 240 | |||||||||
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| Publications: | None | |||||||||
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| SDY2475: Neutralizing Monoclonal Antibodies That Target the Spike Receptor | |||||||
| Status: | New | ||||||
| Description: | To delineate the roles of neutralizing and non-neutralizing antibodies against SARS-CoV-2, we compared the protective effect of a potently neutralizing MAb (2B04) (50 percent inhibitory concentration [IC50] of 0.04 ug/ml), a weakly neutralizing MAb (2C03) (IC50 of 5 ug/ml), and two minimal neutralizing MAbs (2C02 and 2E06) (IC50 20 ug/ml) in Syrian hamsters and determined the role of Fc receptor interactions on protection. We find that the potently neutralizing MAb 2B04 reduces viral burden and disease severity when given as a pre- or post-exposure therapy. | ||||||
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| DOI: | 10.21430/M3MT487UGA | ||||||
| Subjects: | 131 | ||||||
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| Publications: | None | ||||||
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| SDY2476: An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | Carreno et al. collected human serum samples for the NDV-HXP-S vaccine clinical trial (phase 1) and performed secondary analysis to determine antibody characteristics according to each cohort. | ||||||||||||||||||
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| DOI: | 10.21430/M31QAVJZD3 | ||||||||||||||||||
| Subjects: | 248 | ||||||||||||||||||
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| Publications: | None | ||||||||||||||||||
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| SDY2477: Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster | |||||||||||||
| Status: | New | ||||||||||||
| Description: | The emergence of the highly divergent B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to concerns about the efficacy of vaccines based on the ancestral spike and to the approval in the United States of bivalent vaccines for coronavirus disease 2019 (Covid-19) that include the ancestral spike and the omicron BA.5 spike proteins. Since the approval and distribution of these vaccines, additional subvariants containing key mutations that further enhance the ability of the virus to escape from vaccine-elicited antibodies and regulatory-approved monoclonal antibodies have been identified.4 Of particular concern is the R346T mutation, which has arisen in multiple omicron subvariants, including BA.2.75.2, BQ.1.1, and XBB (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). We tested serum samples obtained from participants who had received either one or two monovalent boosters or the bivalent booster to determine the neutralization efficiency of the booster vaccines against wild-type (WA1/2020) virus and primary isolates of omicron subvariants BA.1, BA.5, BA.2.75.2, BQ.1.1, and XBB using an in vitro, live-virus focus reduction neutralization test (FRNT). All the participants provided written informed consent | ||||||||||||
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| DOI: | 10.21430/M37KGVOLUJ | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2478: Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population | |||||||||||||
| Status: | New | ||||||||||||
| Description: | The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern. | ||||||||||||
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| DOI: | 10.21430/M3E161I9ZM | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2479: SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | The spike aspartic acid-614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models | |||||||||||||||
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| DOI: | 10.21430/M3HRBT1JY9 | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2480: Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in ""mouse-adapted"" SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera. | |||||||||||||||
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| DOI: | 10.21430/M38LNCNWUO | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2481: Rapid Detection and Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant in a Returning Traveler | |||||||
| Status: | New | ||||||
| Description: | We describe rapid detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant using targeted spike single-nucleotide polymorphism polymerase chain reaction and viral genome sequencing. This case occurred in a fully vaccinated and boosted returning traveler with mild symptoms who was identified through community surveillance rather than clinical care. | ||||||
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| DOI: | 10.21430/M3APSDUT0P | ||||||
| Subjects: | 0 | ||||||
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| SDY2482: Estimated preventable COVID-19-associated deaths due to non-vaccination in the United States | ||||||||||
| Status: | New | |||||||||
| Description: | While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to vaccinate. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in the US from May 30, 2021 to September 3, 2022 adjusted for the effects of age and time. We estimated that at least 232,000 deaths could have been prevented among unvaccinated adults during the 15 months had they been vaccinated with at least a primary series. While uncertainties exist regarding the exact number of preventable deaths and more granular data are needed on other factors causing differences in death rates between the vaccinated and unvaccinated groups to inform these estimates, this method is a rapid assessment on vaccine-preventable deaths due to SARS-CoV-2 that has crucial public health implications. The same rapid method can be used for future public health emergencies. | |||||||||
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| DOI: | 10.21430/M3MTSYRBG6 | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2486: Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals | ||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||
| Description: | The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2 months after infection or the reason for the discrepancy in COVID-19 disease and sex. Using convalescent-phase sera collected from 101 COVID-19-recovered individuals 21 to 212 days after symptom onset with 48 additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations of individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to 6 months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex and in individuals with cardiometabolic comorbidities. IMPORTANCE In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardiometabolic comorbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2 which supports the growing literature on sex discrepancies regarding COVID-19 disease morbidity and mortality, as well as functional neutralizing antibody responses to SARS-CoV-2. | |||||||||||||||||||||
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| DOI: | 10.21430/M3RS4Y8FXD | |||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||
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| SDY2487: New-onset IgG autoantibodies in hospitalized patients with COVID-19 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins. | ||||||||||||
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| DOI: | 10.21430/M3QT02OJLO | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| SDY2488: Discrete SARS-CoV-2 antibody titers track with functional humoral stability | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses. | |||||||||||||||
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| DOI: | 10.21430/M3OB38FUZ9 | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| SDY2489: Utility of Newborn Dried Blood Spots to Ascertain Seroprevalence of SARS-CoV-2 Antibodies Among Individuals Giving Birth in New York State, November 2019 to November 2021 | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Importance: Serosurveys can be used to monitor population-level dynamics of COVID-19 and vaccination. Dried blood spots (DBSs) collected from infants contain maternal IgG antibodies and are useful for serosurveys of individuals recently giving birth. Objectives: To examine SARS-CoV-2 antibody prevalence in pregnant individuals in New York State, identify associations between SARS-CoV-2 antibody status and maternal and infant characteristics, and detect COVID-19 vaccination among this population. Design, setting, and participants: A population-based, repeated cross-sectional study was conducted to detect SARS-CoV-2 nucleocapsid (N) and spike (S) IgG antibodies. Deidentified DBS samples and data submitted to the New York State Newborn Screening Program between November 1, 2019, and November 30, 2021, were analyzed. Exposures: Prenatal exposure to SARS-CoV-2 antibodies. Main outcomes and measures: The presence of IgG antibodies to SARS-CoV-2 N and S antigens was measured using a microsphere immunoassay. Data were analyzed by geographic region and compared with reported COVID-19 cases and vaccinations among reproductive-aged females (15-44 years of age). Data were stratified by infant birth weight, gestational age, maternal age, and multiple birth status. Results: Dried blood spot samples from 415 293 infants (median [IQR] age, 1.04 [1.00-1.20] days; 210 805 [51.1%] male) were analyzed for SARS-CoV-2 antibodies. The first known antibody-positive infant in New York State was born on March 29, 2020. SARS-CoV-2 seroprevalence reflected statewide and regional COVID-19 cases among reproductive-aged females in the prevaccine period. From February through November 2021, S seroprevalence was strongly correlated with cumulative vaccinations in each New York State region and in the state overall (rs = 0.92-1.00, P ≤ .001). S and N seroprevalences were significantly lower in newborns with very low birth weight (720 [14.8%] for S and 138 [2.8%] for N, P < .001) and low birth weight (5160 [19.3%] for S and 1233 [4.6%] for N, P = .009) compared with newborns with normal birth weight (77 116 [20.1%] for S and 19 872 [5.2%] for N). Lower N and higher S seroprevalences were observed in multiple births (odds ratio [OR], 0.84; 95% CI, 0.75-0.94; P = .002 for N and OR, 1.24; 95% CI, 1.18-1.31; P < .001 for S) vs single births and for maternal age older than 30 years (OR, 0.87; 95% CI, 0.80-0.94; P < .001 for N and OR, 1.17; 95% CI, 1.11-1.23; P < .001 for S) vs younger than 20 years. Conclusions and relevance: In this study, seroprevalence in newborn DBS samples reflected COVID-19 case fluctuations and vaccinations among reproductive-aged women during the study period. These results demonstrate the utility of using newborn DBS testing to estimate SARS-CoV-2 seroprevalence in pregnant individuals. | ||||||||||||
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| DOI: | 10.21430/M3VEGJT4R2 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| SDY2490: An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and -2 has resulted in the discovery of numerous animal sarbecoviruses-the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and -2, the RBD from one virus, Khosta 2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2. | |||||||||||||||
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| DOI: | 10.21430/M3YT6O5FZQ | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
Updated Studies
| SDY1944: Flow cytometer data for investigation into an integrated microfluidic system for basophil isolation from whole blood | ||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||
| Description: | Purity and recovery of basophils isolated from 100 uL of whole blood are measured for the integrated system and subcomponents of the system; artificial activation of basophils by the integrated system is quantified, and basophils are shown to be functional in downstream activation experiments. | |||||||||||||||||||||
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| DOI: | 10.21430/M3K94PIVEY | |||||||||||||||||||||
| Subjects: | 8 | |||||||||||||||||||||
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| SDY2216: Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination | |||||||
| Status: | Updated | ||||||
| Description: | Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination. | ||||||
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| DOI: | 10.21430/M365O4LM7J | ||||||
| Subjects: | 0 | ||||||
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