Evidence map›Paper›PMID 30566602›Full record

Trial reportThe Journal of infectious diseases2019

AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells.

Leigh M Howard, Johannes B Goll, Travis L Jensen, Kristen L Hoek, Nripesh Prasad, Casey E Gelber, Shawn E Levy, Sebastian Joyce, Andrew J Link, C Buddy Creech and 1 more

Abstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Emerging and Pandemic Pathogens: Lessons Learned From a Clinical Research Network.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Leigh M HowardVanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Johannes B GollThe Emmes Corporation, Rockville, Maryland.
Travis L JensenThe Emmes Corporation, Rockville, Maryland.
Kristen L HoekDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Nripesh PrasadHudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
Casey E GelberThe Emmes Corporation, Rockville, Maryland.
Shawn E LevyHudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
Sebastian JoyceDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Andrew J LinkDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
C Buddy CreechVanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Kathryn M EdwardsVanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Childhood Infections Research ProgramT32AI095202 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JAMES E CASSAT · 2011 to 2026
$4.2M
Proteomic Analysis of Eukaryotic Protein SynthesisR01GM064779 · NIGMS · VANDERBILT UNIVERSITY · PI LINK, ANDREW J. · 2002 to 2010
$3.0M
Molecular Basis of CD1D and Natural Killer T Cell FunctionR01AI137082 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JOYCE, SEBASTIAN · 2019 to 2022
$2.1M
Processing and Presentation of Minor Histocompatibility Antigens that Cause GvHDR01HL121139 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JOYCE, SEBASTIAN · 2014 to 2017
$1.6M
Vaccinating at Mucosal Surfaces with Nanoparticle Conjugated Antigen and AdjuvantI01BX001444 · VA · VETERANS HEALTH ADMINISTRATION · PI JOYCE, SEBASTIAN · 2014 to 2022
–
BLRD Research Career Scientist Award ApplicationIK6BX004595 · VA · VETERANS HEALTH ADMINISTRATION · PI JOYCE, SEBASTIAN · 2019 to 2025
–
BLRD VA I01 BX001444BLRD VA IK6 BX004595NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NCRR NIH HHS UL1 RR024975NHLBI NIH HHS R01 HL121139NIAID NIH HHS HHSN272200800007CNIAID NIH HHS HHSN272201300023INIAID NIH HHS R01 AI137082NIAID NIH HHS T32 AI095202NIDDK NIH HHS P30 DK058404NIGMS NIH HHS R01 GM064779
6 · The paper itself

Abstract

backgroundAdjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood.

methodsUsing ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types.

resultsAS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs.

conclusionsTranscriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.

Indexed as

Immunity, InnateAdaptive ImmunityAdjuvants, ImmunologicAdultalpha-TocopherolDouble-Blind MethodDrug CombinationsGene Expression ProfilingHumansInfluenza A Virus, H5N1 SubtypeInfluenza, HumanInfluenza VaccinesLeukocytesPolysorbatesSignal TransductionSqualeneAdjuvants, Immunologicalpha-TocopherolAS03 adjuvantDrug CombinationsInfluenza VaccinesPolysorbatesSqualeneadjuvantAS03avian influenzainfluenza vaccinesystems vaccinology

Identifiers

PMID30566602
PMCPMC6500554

What OpenQuestion holds

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Registered trials

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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.