Evidence map›Paper›PMID 28049494›Full record

ArticleJournal of translational medicine2017

Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response.

Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

103 citing papers in PubMed, 184 citations in OpenAlex.

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43 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 3 countries.

Darin K EdwardsSanofi Pasteur, VaxDesign Campus, 2501 Discovery Drive Suite 300, Orlando, FL, USA. darin.edwards@sanofipasteur.com.ORCID 0000-0001-5977-6258
Edith JasnyCureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
Heesik YoonSanofi Pasteur, VaxDesign Campus, 2501 Discovery Drive Suite 300, Orlando, FL, USA.
Nigel HorscroftCureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
Brian SchanenSanofi Pasteur, VaxDesign Campus, 2501 Discovery Drive Suite 300, Orlando, FL, USA.
Tanya GeterSanofi Pasteur, VaxDesign Campus, 2501 Discovery Drive Suite 300, Orlando, FL, USA.
Mariola Fotin-MleczekCureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
Benjamin PetschCureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
Vaughan WittmanSanofi Pasteur, VaxDesign Campus, 2501 Discovery Drive Suite 300, Orlando, FL, USA.
CureVac (Germany) · DESanofi (United States) · USSanofi (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProphylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species.

methodsIn this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model. This evaluation was performed using an in vitro model of human innate immunity and in vivo in mice after intradermal injection.

resultsResults suggest that immunostimulation from the mRNA vaccine in humans is similar to that in mice and acts through cellular RNA sensors, with genes for RLRs [ddx58 (RIG-1) and ifih1 (MDA-5)], TLRs (tlr3, tlr7, and tlr8-human only), and CLRs (clec4gp1, clec2d, cledl1) all significantly up-regulated by the mRNA vaccine. The up-regulation of TLR8 and TLR7 points to the involvement of both mDCs and pDCs in the response to the mRNA vaccine in humans. In both humans and mice activation of these pathways drove maturation and activation of immune cells as well as production of cytokines and chemokines known to attract and activate key players of the innate and adaptive immune system.

conclusionThis translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models.

Indexed as

Genetic EngineeringTranslational Research, BiomedicalAdjuvants, ImmunologicAnimalsBase SequenceDose-Response Relationship, ImmunologicGene Expression RegulationGene Regulatory NetworksHumansImmunity, InnateInfluenza VaccinesLymph NodesMice, Inbred C57BLRNA, MessengerAdjuvants, ImmunologicInfluenza VaccinesRNA, MessengerAdjuvantCLRsHumanInnateIn vitroMIMICMousemRNARLRsSelf-adjuvantationTLRsVaccine

Identifiers

PMID28049494
PMCPMC5210268
OpenAlexW2567689582

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.