Evidence map›Paper›PMID 34686605›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

J Gutiérrez-Álvarez, J M Honrubia, A Sanz-Bravo, E González-Miranda, R Fernández-Delgado, M T Rejas, S Zúñiga, I Sola, L Enjuanes

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. SARS-CoV-2-derived RNA replicons as safe and effective vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Viral Replicon Systems and Their Biosafety Aspects.Applied biosafety : journal of the American Biological Safety Association · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Nature of viruses and pandemics: Coronaviruses.Current research in immunology · 2022
    Review
  13. Review
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 2 institutions in 1 country.

J Gutiérrez-ÁlvarezDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.ORCID 0000-0003-0690-9496
J M HonrubiaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.
A Sanz-BravoDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.
E González-MirandaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.
R Fernández-DelgadoDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.
M T RejasElectron Microscopy Service, Centro de Biología Molecular "Severo Ochoa" (CBMSO-CSIC-UAM), Universidad Autónoma de Madrid, Madrid 28049, Spain.
S ZúñigaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.ORCID 0000-0003-2549-6826
I SolaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain.ORCID 0000-0002-5704-1917
L EnjuanesDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid 28049 Madrid, Spain; l.enjuanes@cnb.csic.es.ORCID 0000-0002-0854-0226
Centro Nacional de Biotecnología · ESCentro de Biología Molecular Severo Ochoa · ES

Funding

SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 2004 to 2021
$21.5M
NIAID NIH HHS P01 AI060699
6 · The paper itself

Abstract

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.

Indexed as

RepliconAnimalsAntibodies, NeutralizingAntibodies, ViralCoronavirus InfectionsDefective VirusesFemaleGene DeletionGenes, envHumansMiceMice, Inbred C57BLMice, TransgenicMiddle East Respiratory Syndrome CoronavirusRNA, ViralVaccines, DNAAntibodies, NeutralizingAntibodies, ViralMiddle East respiratory syndrome vaccineRNA, ViralVaccines, DNAVaccines, Virus-Like ParticleViral VaccinescoronavirusMERS-CoVRNA repliconvaccine

Identifiers

PMID34686605
PMCPMC8639359
OpenAlexW3207812616

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.