Evidence map›Paper›PMID 26640818›Full record

ArticleACS central science2015

Modulation of Innate Immune Responses

Janine K Tom, Emmanuel Y Dotsey, Hollie Y Wong, Lalisa Stutts, Troy Moore, D Huw Davies, Philip L Felgner, Aaron P Esser-Kahn

Open access · diamondAbstract read
In one paragraph

Article in ACS central science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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

38 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
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  10. Synthesis and Optimization of 1-Substituted Imidazo[4,5-ACS medicinal chemistry letters · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. A nanovaccine for enhancing cellular immunity via cytosolic co-delivery of antigen and polyIC RNA.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  16. Article
  17. Review
  18. Article
  19. Review
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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

8 authors at 1 institution in 1 country.

Janine K TomDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Emmanuel Y DotseyDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Hollie Y WongDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Lalisa StuttsDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Troy MooreDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
D Huw DaviesDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Philip L FelgnerDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
Aaron P Esser-KahnDepartment of Chemistry and Department of Medicine, Division of Infectious Diseases, University of California, Irvine , Irvine, California 92697, United States.
University of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
Multiplex Serodiagnostic Protein MicroarrayU01AI078213 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI FELGNER, PHILIP LOUIS · 2008 to 2012
$3.7M
Seriodiagnostic arrays for biodefense and emerging infectious diseasesR44AI058365 · NIAID · IMMPORT THERAPEUTICS, INC. · PI DAVIES, DAVID HUW · 2008 to 2010
$3.0M
Directing The Immune System Via Polymeric Combinations of Molecular SignalsDP2AI112194 · NIAID · UNIVERSITY OF CHICAGO · PI ESSER-KAHN, AARON P · 2013 to 2013
$2.3M
NCI NIH HHS P30 CA062203NIAID NIH HHS DP2 AI112194NIAID NIH HHS R44 AI058365NIAID NIH HHS U01 AI078213
6 · The paper itself

Abstract

We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed

Identifiers

PMID26640818
PMCPMC4665084
OpenAlexW2195278272

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.