Evidence map›Paper›PMID 31163034›Full record

ArticlePloS one2019

Delivery of self-amplifying RNA vaccines in in vitro reconstituted virus-like particles.

Adam Biddlecome, Habtom H Habte, Katherine M McGrath, Sharmila Sambanthamoorthy, Melanie Wurm, Martina M Sykora, Charles M Knobler, Ivo C Lorenz, Marcio Lasaro, Knut Elbers and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
9.3field-weighted citation impact, top 3% 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

39 citing papers in PubMed, 63 citations in OpenAlex.

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  14. Molecular pharmaceutics · 2024
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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

11 authors at 5 institutions in 3 countries.

Adam BiddlecomeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, California, United States of America.
Habtom H HabteBoehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States of America.
Katherine M McGrathBoehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States of America.
Sharmila SambanthamoorthyBoehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States of America.
Melanie WurmBoehringer-Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Martina M SykoraBoehringer-Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Charles M KnoblerDepartment of Chemistry and Biochemistry, University of California, Los Angeles, California, United States of America.
Ivo C LorenzTri-Institutional Therapeutics Discovery Institute, New York, New York, United States of America.ORCID 0000-0002-7373-1176
Marcio LasaroBoehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States of America.
Knut ElbersBoehringer-Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
William M GelbartDepartment of Chemistry and Biochemistry, University of California, Los Angeles, California, United States of America.ORCID 0000-0003-2125-4256
Boehringer Ingelheim (United States) · USUniversity of California, Los Angeles · USBoehringer Ingelheim (Austria) · ATBoehringer Ingelheim (Germany) · DETri-Institutional Therapeutics Discovery Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many mRNA-based vaccines have been investigated for their specific potential to activate dendritic cells (DCs), the highly-specialized antigen-presenting cells of the immune system that play a key role in inducing effective CD4+ and CD8+ T-cell responses. In this paper we report a new vaccine/gene delivery platform that demonstrates the benefits of using a self-amplifying ("replicon") mRNA that is protected in a viral-protein capsid. Purified capsid protein from the plant virus Cowpea Chlorotic Mottle Virus (CCMV) is used to in vitro assemble monodisperse virus-like particles (VLPs) containing reporter proteins (e.g., Luciferase or eYFP) or the tandem-repeat model antigen SIINFEKL in RNA gene form, coupled to the RNA-dependent RNA polymerase from the Nodamura insect virus. Incubation of immature DCs with these VLPs results in increased activation of maturation markers - CD80, CD86 and MHC-II - and enhanced RNA replication levels, relative to incubation with unpackaged replicon mRNA. Higher RNA uptake/replication and enhanced DC activation were detected in a dose-dependent manner when the CCMV-VLPs were pre-incubated with anti-CCMV antibodies. In all experiments the expression of maturation markers correlates with the RNA levels of the DCs. Overall, these studies demonstrate that: VLP protection enhances mRNA uptake by DCs; coupling replicons to the gene of interest increases RNA and protein levels in the cell; and the presence of anti-VLP antibodies enhances mRNA levels and activation of DCs in vitro. Finally, preliminary in vivo experiments involving mouse vaccinations with SIINFEKL-replicon VLPs indicate a small but significant increase in antigen-specific T cells that are doubly positive for IFN and TFN induction.

Indexed as

AnimalsBromovirusCapsid ProteinsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell LineCricetinaeDendritic CellsFemaleGenetic VectorsMiceRNA, MessengerSingle-Cell AnalysisVaccines, Virus-Like ParticleVirus AssemblyCapsid ProteinsRNA, MessengerVaccines, Virus-Like Particle

Identifiers

PMID31163034
PMCPMC6548422
OpenAlexW2948669956

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.