Evidence map›Paper›PMID 34174187›Full record

Trial reportCell2021

The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.

Florian Wimmers, Michele Donato, Alex Kuo, Tal Ashuach, Shakti Gupta, Chunfeng Li, Mai Dvorak, Mariko Hinton Foecke, Sarah E Chang, Thomas Hagan and 13 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06667063 (Clinical Study on the Immune Response Characteristics of Novel Coronavirus and Influenza Virus Infection), which is not on this map. Cited by 168 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06667063 recruitingnot on this mapstarted 2024, after this paper: background citation

Clinical Study on the Immune Response Characteristics of Novel Coronavirus and Influenza Virus Infection

Typeobservational_patient_registrySponsorZhongnan HospitalRan2024 to 2025Enrolled130ConditionsCOVID-19, InfluenzaArmsNasal swab/Nasopharyngeal swab/Blood sample collection, Nasal swab/Nasopharyngeal swab/Blood draw
3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Single-cell RNA sequencing offers novel perspectives in viral infection research.Frontiers in cellular and infection microbiology · 2026
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108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Florian WimmersInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michele DonatoInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alex KuoInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Tal AshuachDepartment of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Shakti GuptaDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093, USA.
Chunfeng LiInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mai DvorakInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mariko Hinton FoeckeInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sarah E ChangInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Thomas HaganInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sanne E De JongInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Holden T MaeckerInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Robbert van der MostGSK, 1330 Rixensart, Belgium.
Peggie CheungDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mario CorteseInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Steven E BosingerEmory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Mark DavisInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Nadine RouphaelHope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Shankar SubramaniamDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093, USA.
Nir YosefDepartment of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan-Zuckerberg Biohub, San Francisco, CA, USA.
Paul J UtzInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Purvesh KhatriInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bali PulendranInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: bpulend@stanford.edu.

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Regional Biocontainment Laboratory (RBL)UC6AI058607 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, R SANDERS · 2003 to 2005
$16.3M
MICROBES, DENDRITIC CELL SUBSETS AND T-CELL IMMUNITYR01AI048638 · NIAID · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2001 to 2024
$4.5M
Illumina NovaSeq 6000 High Throughput DNA Sequencer for Emory UniversityS10OD026799 · OD · EMORY UNIVERSITY · PI BOSINGER, STEVEN EDWARD · 2019 to 2019
$985k
Microbes, Dendritic Cell Subsets and T-Cell ImmunityR56AI048638 · NIAID · EMORY UNIVERSITY · PI PULENDRAN, BALI · 2008 to 2008
$440k
NIAID NIH HHS R01 AI048638NIAID NIH HHS R56 AI048638NIAID NIH HHS U19 AI057266NIAID NIH HHS U19 AI090023NIAID NIH HHS UC6 AI058607NIH HHS P51 OD011132NIH HHS S10 OD026799
6 · The paper itself

Abstract

Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.

Indexed as

EpigenomicsSingle-Cell AnalysisTranscription, GeneticVaccinationAdolescentAdultalpha-TocopherolAnti-Bacterial AgentsAntigens, CD34Cellular ReprogrammingChromatinCytokinesDrug CombinationsFemaleGene Expression RegulationHistonesalpha-TocopherolAnti-Bacterial AgentsAntigens, CD34AS03 adjuvantChromatinCytokinesDrug CombinationsHistonesInfluenza VaccinesInterferon Type IPolysorbatesSqualeneToll-Like ReceptorsTranscription Factor AP-1adjuvantantiviral immunityepigenomeinfluenzainnate memorymonocytesingle cellsystems biologytrained immunityvaccines

Identifiers

PMID34174187
PMCPMC8316438

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.