Evidence map›Paper›PMID 33722288›Full record

ArticleGenome medicine2021

SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription.

Abdulaziz Almuqrin, Andrew D Davidson, Maia Kavanagh Williamson, Philip A Lewis, Kate J Heesom, Susan Morris, Sarah C Gilbert, David A Matthews

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
9.5field-weighted citation impact, top 1% 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

33 citing papers in PubMed, 60 citations in OpenAlex.

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  15. E4orf1 SuppressesVaccines · 2022
    Article
  16. Article
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  18. SARS-CoV-2 Spike Protein ExpressionFrontiers in immunology · 2022
    Article
  19. Article
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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 3 institutions in 2 countries.

Abdulaziz AlmuqrinSchool of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.
Andrew D DavidsonSchool of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.
Maia Kavanagh WilliamsonSchool of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.
Philip A LewisSchool of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.
Kate J HeesomProteomics Facility, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.
Susan MorrisJenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Sarah C GilbertJenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
David A MatthewsSchool of Cellular and Molecular Medicine, Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK. d.a.matthews@bristol.ac.uk.ORCID 0000-0003-4611-8795
University of Bristol · GBUniversity of Oxford · GBKing Saud University · SA

Funding

Biotechnology and Biological Sciences Research Council BB/M02542X/1Engineering and Physical Sciences Research Council EP/R013756/1U.S. Food and Drug Administration HHSF223201510104C
6 · The paper itself

Abstract

backgroundChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to the cell nucleus alongside the SARS-CoV-2 S glycoprotein gene.

methodsWe used direct RNA sequencing to analyse transcript expression from the ChAdOx1 nCoV-19 genome in human MRC-5 and A549 cell lines that are non-permissive for vector replication alongside the replication permissive cell line, HEK293. In addition, we used quantitative proteomics to study over time the proteome and phosphoproteome of A549 and MRC5 cells infected with the ChAdOx1 nCoV-19 vaccine.

resultsThe expected SARS-CoV-2 S coding transcript dominated in all cell lines. We also detected rare S transcripts with aberrant splice patterns or polyadenylation site usage. Adenovirus vector transcripts were almost absent in MRC-5 cells, but in A549 cells, there was a broader repertoire of adenoviral gene expression at very low levels. Proteomically, in addition to S glycoprotein, we detected multiple adenovirus proteins in A549 cells compared to just one in MRC5 cells.

conclusionsOverall, the ChAdOx1 nCoV-19 vaccine's transcriptomic and proteomic repertoire in cell culture is as expected. The combined transcriptomic and proteomics approaches provide a detailed insight into the behaviour of this important class of vaccine using state-of-the-art techniques and illustrate the potential of this technique to inform future viral vaccine vector design.

Indexed as

Cell LineCells, CulturedCOVID-19COVID-19 VaccinesGene ExpressionGene Expression ProfilingGene Expression RegulationHost-Pathogen InteractionsHumansPolyadenylationProteomicsRNA, MessengerRNA, ViralSARS-CoV-2Spike Glycoprotein, CoronavirusTranscription, GeneticCOVID-19 VaccinesRNA, MessengerRNA, ViralSpike Glycoprotein, Coronavirus

Identifiers

PMID33722288
PMCPMC7958140
OpenAlexW3134318926

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.