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Article ; Online: Erythema and Induration after Mpox (JYNNEOS) Vaccination Revisited.

Frey, Sharon E / Goll, Johannes B / Beigel, John H

2023 Volume 388, Issue 15, Page(s) 1432–1435

MeSH term(s)	Humans ; Erythema/chemically induced ; Erythema/etiology ; Mpox (monkeypox)/prevention & control ; Vaccination/adverse effects ; Vaccines, Attenuated/adverse effects ; Vaccines, Attenuated/therapeutic use ; Smallpox Vaccine/adverse effects ; Smallpox Vaccine/therapeutic use
Chemical Substances	smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic (TU8J357395) ; Vaccines, Attenuated ; Smallpox Vaccine
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Letter
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2215846
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Article ; Online: RP-REP

Jensen, Travis L / Hooper, William F / Cherikh, Sami R / Goll, Johannes B

F1000Research

2021 Volume 10, Page(s) 143

Abstract: Ribosomal profiling is an emerging experimental technology to measure protein synthesis by sequencing short mRNA fragments undergoing translation in ribosomes. Applied on the genome wide scale, this is a powerful tool to profile global protein synthesis ... ...

Abstract	Ribosomal profiling is an emerging experimental technology to measure protein synthesis by sequencing short mRNA fragments undergoing translation in ribosomes. Applied on the genome wide scale, this is a powerful tool to profile global protein synthesis within cell populations of interest. Such information can be utilized for biomarker discovery and detection of treatment-responsive genes. However, analysis of ribosomal profiling data requires careful preprocessing to reduce the impact of artifacts and dedicated statistical methods for visualizing and modeling the high-dimensional discrete read count data. Here we present Ribosomal Profiling Reports (RP-REP), a new open-source cloud-enabled software that allows users to execute start-to-end gene-level ribosomal profiling and RNA-Seq analysis on a pre-configured Amazon Virtual Machine Image (AMI) hosted on AWS or on the user's own Ubuntu Linux server. The software works with FASTQ files stored locally, on AWS S3, or at the Sequence Read Archive (SRA). RP-REP automatically executes a series of customizable steps including filtering of contaminant RNA, enrichment of true ribosomal footprints, reference alignment and gene translation quantification, gene body coverage, CRAM compression, reference alignment QC, data normalization, multivariate data visualization, identification of differentially translated genes, and generation of heatmaps, co-translated gene clusters, enriched pathways, and other custom visualizations. RP-REP provides functionality to contrast RNA-SEQ and ribosomal profiling results, and calculates translational efficiency per gene. The software outputs a PDF report and publication-ready table and figure files. As a use case, we provide RP-REP results for a dengue virus study that tested cytosol and endoplasmic reticulum cellular fractions of human Huh7 cells pre-infection and at 6 h, 12 h, 24 h, and 40 h post-infection. Case study results, Ubuntu installation scripts, and the most recent RP-REP source code are accessible at GitHub. The cloud-ready AMI is available at AWS (AMI ID: RPREP RSEQREP (Ribosome Profiling and RNA-Seq Reports) v2.1 (ami-00b92f52d763145d3)).
Language	English
Publishing date	2021-02-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.40668.1
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Article ; Online: Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

Howard, Leigh M / Jensen, Travis L / Goll, Johannes B / Gelber, Casey E / Bradley, Matthew D / Sherrod, Stacy D / Hoek, Kristen L / Yoder, Sandra / Jimenez-Truque, Natalia / Edwards, Kathryn / Creech, C Buddy

The Journal of infectious diseases

2024

Abstract: Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.: Methods: Twenty healthy men and women (18-49 years of age) were ... ...

Abstract	Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants. Methods: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization. Results: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without. Conclusions: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad611
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Article ; Online: Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures.

Hamzabegovic, Fahreta / Goll, Johannes B / Hooper, William F / Frey, Sharon / Gelber, Casey E / Abate, Getahun

NPJ vaccines

2020 Volume 5, Issue 1, Page(s) 6

Abstract: ... Yersinia ... ...

Abstract	Yersinia pestis
Keywords	covid19
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-020-0156-y
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Article ; Online: Distinct gene expression signatures comparing latent tuberculosis infection with different routes of Bacillus Calmette-Guérin vaccination.

Silver, Richard F / Xia, Mei / Storer, Chad E / Jarvela, Jessica R / Moyer, Michelle C / Blazevic, Azra / Stoeckel, David A / Rakey, Erin K / Tennant, Jan M / Goll, Johannes B / Head, Richard D / Hoft, Daniel F

Nature communications

2023 Volume 14, Issue 1, Page(s) 8507

Abstract: Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal ... ...

Abstract	Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated with robust systemic immunity but only limited pulmonary immunity. Conversely, oral BCG induces limited systemic immunity but distinct pulmonary responses including enhanced inflammasome activation potentially associated with mucosal-associated invariant T cells. Further, IL-9 is identified as a component of systemic immunity in LTBI and intradermal BCG, and pulmonary immunity following oral BCG.
MeSH term(s)	Humans ; Latent Tuberculosis ; BCG Vaccine ; Mycobacterium tuberculosis/genetics ; Transcriptome ; Tuberculosis/prevention & control ; Vaccination ; Mycobacterium bovis
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2023-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44136-8
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Article ; Online: Corrigendum: The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies.

Goll, Johannes B / Bosinger, Steven E / Jensen, Travis L / Walum, Hasse / Grimes, Tyler / Tharp, Gregory K / Natrajan, Muktha S / Blazevic, Azra / Head, Richard D / Gelber, Casey E / Steenbergen, Kristen J / Patel, Nirav B / Sanz, Patrick / Rouphael, Nadine G / Anderson, Evan J / Mulligan, Mark J / Hoft, Daniel F

Frontiers in immunology

2023 Volume 14, Page(s) 1163550

Abstract: This corrects the article DOI: 10.3389/fimmu.2022.1093242.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1163550
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Article ; Online: The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies.

Frontiers in immunology

2023 Volume 13, Page(s) 1093242

Abstract: Introduction: Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of ... ...

Abstract	Introduction: Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of this study was to benchmark key technical and analytical parameters of RNA sequencing (RNA-seq) in the context of a multi-site, double-blind randomized vaccine clinical trial. Methods: We collected longitudinal peripheral blood mononuclear cell (PBMC) samples from 10 subjects before and after vaccination with a live attenuated Results and discussion: Our results showed that (i) filtering lowly-expressed genes is recommended to improve fold-change accuracy and inter-site agreement, if possible guided by mRNA spike-ins (ii) read length did not have a major impact on DEG detection, (iii) applying fold-change cutoffs for DEG detection reduced inter-set agreement and should be used with caution, if at all, (iv) reduction in sequencing depth had a minimal impact on statistical power but reduced the identifiable fraction of the PBMC transcriptome, (v) after sample size, effect size (i.e. the magnitude of fold change) was the most important driver of statistical power to detect DEG. The results from this study provide RNA sequencing benchmarks and guidelines for planning future similar vaccine studies.
MeSH term(s)	Humans ; RNA-Seq ; Benchmarking ; Leukocytes, Mononuclear ; Vaccines, Attenuated ; RNA, Messenger/genetics
Chemical Substances	Vaccines, Attenuated ; RNA, Messenger
Language	English
Publishing date	2023-01-19
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1093242
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Article ; Online: Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence.

Miller, Christopher A / Walker, Jason R / Jensen, Travis L / Hooper, William F / Fulton, Robert S / Painter, Jeffrey S / Sekeres, Mikkael A / Ley, Timothy J / Spencer, David H / Goll, Johannes B / Walter, Matthew J

The Journal of molecular diagnostics : JMD

2022 Volume 24, Issue 3, Page(s) 219–223

Abstract: The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the ... ...

Abstract	The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.
MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Splicing Factor U2AF/genetics
Chemical Substances	Splicing Factor U2AF ; U2AF1 protein, human
Language	English
Publishing date	2022-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/j.jmoldx.2021.10.013
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Article ; Online: The antibody landscapes following AS03 and MF59 adjuvanted H5N1 vaccination.

Goll, Johannes B / Jain, Aarti / Jensen, Travis L / Assis, Rafael / Nakajima, Rie / Jasinskas, Algis / Coughlan, Lynda / Cherikh, Sami R / Gelber, Casey E / Khan, S / Huw Davies, D / Meade, Philip / Stadlbauer, Daniel / Strohmeier, Shirin / Krammer, Florian / Chen, Wilbur H / Felgner, Philip L

NPJ vaccines

2022 Volume 7, Issue 1, Page(s) 103

Abstract: Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, ... ...

Abstract	Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full-length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and heterosubtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. The adjuvanted vaccine was also associated with the elicitation of stalk-directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.
Language	English
Publishing date	2022-08-30
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-022-00524-7
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Article ; Online: Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.

Blazevic, Azra / Edwards, Rachel L / Xia, Mei / Eickhoff, Christopher S / Hamzabegovic, Fahreta / Meza, Krystal A / Ning, Huan / Tennant, Janice / Mosby, Karla J / Ritchie, James C / Girmay, Tigisty / Lai, Lilin / McCullough, Michele / Beck, Allison / Kelley, Colleen / Edupuganti, Srilatha / Kabbani, Sarah / Buchanan, Wendy / Makhene, Mamodikoe K /

Voronca, Delia / Cherikh, Sami / Goll, Johannes B / Rouphael, Nadine G / Mulligan, Mark J / Hoft, Daniel F

The Journal of infectious diseases

2023

Abstract: Background: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development.: Methods: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to ... ...

Abstract	Background: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. Methods: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. Results: Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. Conclusions: The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. Clinical trials registration: NCT01868464 (ClinicalTrials.gov).
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad441
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